CA3085488C - Transdermal analgesic formulation - Google Patents

Abstract

Provided herein is a transdermal liquid formulation that includes a propionic acid-based non-steroidal anti-inflammatory agent, such as ketoprofen, and a dermal penetration enhancer containing an alcohol, an emollient and an essential oil. Methods of using and making the aforementioned transdermal liquid formulation are also provided herein.

Description

TRANSDERMAL ANALGESIC FORMULATION TECHNICAL FIELD 5 THIS INVENTION relates to a transdermal analgesic formulation for application to the skin of animals, and more particularly cattle.

BACKGROUND Cattle typically undergo a range of necessary surgical husbandry procedures, 10 including dehorning, castration and ovariectomy.

Analgesia may be insufficient during these procedures, especially in extensive properties where access to veterinary assistance is limited.

However, public interest groups and welfare advocates are increasingly concerned about the welfare of animals undergoing potentially painful procedures, while production will also suffer if insufficient analgesia is available.

It would therefore be 15 highly advantageous if analgesics were available and able to be administered without veterinary assistance.

The transdermal route of drug administration offers many advantages, including avoiding first pass effects and the high costs of producing parenteral formulations (particularly sterility), plus can be easily administered by lay personnel.

The problem 20 arises that such formulations cannot be extrapolated between species and movement through skin is strongly dependent on the specific active drug and the vehicle the drug is dissolved in.

Accordingly, there remains a need for improved transdermal analgesic formulations for administration to the skin of animals, such as cattle. 25 SUMMARY The present invention is broadly directed to a transdermal liquid formulation that includes a propionic acid-based non-steroidal anti-inflammatory agent, and more particularly ketoprofen, an alcohol, an emollient and an essential oil, as well as methods of use thereof.

The transdermal absorption of the propionic acid-based non-steroidal anti- 30 inflammatory agent can be advantageously enhanced by the inclusion of such a combination of penetration enhancers, such that therapeutica11y relevant concentrations of the anti-inflammatory agent can be rapidly achieved in treated animals.

In a first aspect, the invention provides a transdermal liquid formulation compnsmg: WO 2019/113625 -2- PCT/AU2018/000255 (a) a therapeutically effective amount of a propionic acid-based non-steroidal antiinflammatory agent; and (b) a dermal penetration enhancer comprising an alcohol, an emollient and an essential oil.

Suitably, the propionic acid-based anti-inflammatory agent is selected from the group consisting of ketoprofen, alminoprofen, ibuprofen, oxaprozin, zaltoprofen, tiaprofenic acid, naproxen, fenoprofen, flurbiprofen, pranoprofen, dexibuprofen, dexketoprofen, loxoprofen and any combination thereof.

Preferably, the propionic acidbased non-steroidal anti-inflammatory agent is or comprises ketoprofen or a 10 pharmaceutically acceptable salt thereof.

In certain embodiments, the propionic acid-based non-steroidal anti-inflammatory agent is present in an amount from about 100 mg/mL to about 300 mg/mL.

The alcohol is suitably selected from the group consisting of a primary alcohol, a secondary alcohol and any combination thereof.

Preferably, the alcohol is selected from 15 the group consisting of ethanol, isopropanol and any combination thereof.

More preferably, the alcohol is or comprises ethanol.

In one embodiment, the alcohol is present in an amount from about 100 mL/L to about 700 mL/L.

Suitably, the emollient is selected from the group consisting of a glycol, an 20 unsaturated fatty alcohol, a sorbitol derivative, a myristate, an alkoxylated di-ester of myristyl alcohol and adipic acid, a pyrrolidone, and any combination thereof.

In particular preferred embodiments, the emollient is selected from the group consisting of propylene glycol, oleyl alcohol, dimethyl isosorbide, PPG-3 benzyl ether myristate, di-PPG2- myreth-10-adipate, 1-ethyl-2-pryrrolidone, isomyristate, isopropyl myristate and any 25 combination thereof.

Even more preferably, the emollient is or comprises isopropyl myristate.

In one embodiment, the emo11ient is present in an amount from about 100 mL/L to about 700 mL/L.

Suitably, the essential oil is or comprises menthol, a cineole-based oil or any 30 combination thereof.

Preferably, the cineole-based oil is or comprises eucalyptus oil, eucalyptol or any combination thereof.

In one embodiment, the essential oil is present in an amount from about 25 mL/L to about 150 mL/L.

In particular embodiments, the transdermal liquid formulation is for use in cattle.

WO 2019/113625 -3- PCT/AU2018/000255 In one embodiment, the transdermal liquid formulation is for use as a pour-on preparation.

In one preferred embodiment, the transdermal liquid formulation comprises: ( a) ketoprofen at a concentration of about 100 mg/mL to about 300 mg/mL; (b) ethanol at a concentration of about 300 mL/L to about 600 mL/L; (c) isopropyl myristate at a concentration of about 300 mL/L to about 600 mL/L; and (d) eucalyptus oil at a concentration of about 50 mL/L to about 150 mL/L.

In a second aspect, the invention provides a method of preventing and/or treating 10 inflammation in a subject, the method including the step of administering to the subject a therapeutically effective amount of the transdermal liquid formulation of the first aspect to thereby prevent and/or treat inflammation in the subject.

In a third aspect, the invention provides a method of preventing and/or treating pain in a subject, the method inc1uding the step of administering to the subject a 15 therapeutically effective amount of the transdermal liquid formulation of the first aspect to thereby prevent and/or treat pain in the subject.

In a fourth aspect, the invention provides a method of preventing and/or treating a lameness and/or a loss of mobility in a subject, the method including the step of administering to the subject a therapeutically effective amount of the transdermal liquid 20 formulation of the first aspect to thereby prevent and/or treat the lameness and/or the loss of mobility in the subject.

With respect to the three aforementioned aspects, the transdermal liquid formulation is suitably administered by a spray device, a pour-on device, a spot-on device and/or a transdermal patch. 25 In a fifth aspect, the invention provides a method of administering a transdermal liquid preparation to a subject in need thereof, inc1uding the step of administering a therapeutically effective amount of the transdermal liquid preparation of the first aspect to the subject by an application device.

Suitably, the application device is selected from the group consisting of a spray 30 device, a pour-on device, a spot-on device and a transdermal patch.

In one embodiment, the present method includes the further step of adding the transdermal liquid preparation to the application device.

With respect to the second, third, fourth and fifth aspects, the subject is preferably a mammal.

More preferably, the subject is bovine.

WO 2019/113625 -4- PCT/AU2018/000255 In a sixth aspect, the invention provides a method of preparing a transdermal liquid formulation, including the steps of: (a) combining a therapeutically effective amount of a propionic acid-based nonsteroidal anti-inflammatory agent and a dermal penetration enhancer comprising an 5 alcohol, an emollient and an essential oil; and (b) mixing the mixture of step (a) to thereby prepare the transdermal liquid formulation.

Suitably, the transdermal liquid formulation is that of the first aspect.

In a seventh aspect, the invention provides, a transdermal liquid formulation 10 prepared by the method of the sixth aspect.

As used herein, except where the context requires otherwise, the term "comprise" and variations of the term, such as "comprising", "comprises" and "comprised', are not intended to exclude further elements, components, integers or steps but may include one or more unstated further elements, components, integers or steps. 15 It will be appreciated that the indefinite articles "a" and "an" are not to be read as singular indefinite articles or as otherwise excluding more than one or more than a single subject to which the indefinite article refers.

For example, "a" cell includes one cell, one or more cells and a plurality of cells.

BRIEF DESCRIPTION OF THE DRAWINGS By way of example only, embodiments of the invention are described more fully hereinafter with reference to the accompanying drawing, in which:- Figure l: Permeation profiles of lignocaine hydrochloride through skin obtained from the thorax (TH), dorsal midline (D), ventral abdomen (AB) and scrotum (S).

The cumulative 25 amount is marked on the y-axis.

Each data point represents a mean value and standard error of mean from a number ofreplicates (n = 3).

Figure 2: The mean cumulative of lignocaine hydrochloride in the receptor phase across four regions over 24 hr.

Figure 3: The mean of the amount of lignocaine hydrochloride retained in the skin at the 30 complete of each experiment.

Figure 4: Movement on NSAIDs through cattle skin in vitro.

Figure 5: The effects of various concentrations of ethanol on ketoprofen movement through cattle skin.

WO 2019/113625 - 5 - PCT/AU2018/000255 Figure 6: The effects of various solubilising agents on ketoprofen movement through cattle skin.

Figure 7: The effects of increasing concentration of ketoprofen on the amount of drug penetrating through cattle skin. 5 Figure 8: Appearance of ketoprofen methyl ester in final formulation samples maintained under various conditions.

Figure 9: Co-elution of the ketoprofen transitions and stability of each transition m biological samples.

Figure 10: Calibration curve for analysis of ketoprofen in biological samples. 10 Figure 11: Retention time stability of ketoprofen analysis in biological san1ples (n = 11 shown).

Figure 12: Ketoprofen concentrations (μg/mL) in plasma after transdermal administration of 10 or 40 mL of formulation to four calves.

Figure 13: Ketoprofen concentrations (μg/mL) in plasma after transdermal administration 15 of formulation to four calves.

Figure 14: Plasma concentration vs. time curves for ketoprofen administered to cattle by IV, IM and transdermal routes.

Figure 15: The semi-log arrhythmic graph of the plasma concentration vs. time curves for ketoprofen administered to cattle by IV, IM and transdermal routes. 20 Figure 16: Skin irritation following administration of transdermal ketoprofen formulation.

The figures illustrate the irritation at various time points, with inserts showing a closer view of the actual site of irritation; ( a) calf# 10, 8 days post application (area shaved for biopsy); (b) calf #169: 14 days post application; (c) calf# 181: 27 days post application. 25 Figure 17: Total plasma cortisol (ng/mL) over 96 hr.

Figure 18: Total plasma cortisol (ng/mL) during the first 4 hr only.

Figure 19: A conceptual map of the parameters indicating pain.

Figure 20: Predicted marginal means and prediction intervals.

Figure 21: Analysis of proteins measured in plasma during the clinical study.

DETAILED DESCRIPTION The present invention is predicated, at least in part, on the surprising discovery that the transdermal application of ketoprofen together with specific penetration WO 2019/113625 - 6 - PCT/AU2018/000255 enhancing agents (i.e., an alcohol, an emollient and an essential oil) to cattle rapidly resulted in therapeutically relevant systemic concentrations of the anti-inflammatory agent and provided analgesia that seemed equivalent or even superior to intra-muscular injections of ketoprofen.

Therefore, the formulations of the present invention can be used 5 to prevent or reduce pain or inflammation associated with an infectious disease, surgery, injury, or another cause.

Accordingly, in one aspect, the invention provides a transdermal liquid formulation comprising: (a) a therapeutically effective amount of a propionic acid-based non-steroidal anti- IO inflammatory agent; and (b) a dermal penetration enhancer comprising an alcohol, an emollient and an essential oil.

As generally used herein, the terms "transdermaf', "transdermally" or similar refer to the passage or migration into and/or through the various layers of skin (e.g. 15 stratum corneum, dermis, cutis and subcutis) and/or mucosa for localized or systemic delivery of an active agent to a subject.

Transdermal application of the formulation of the present aspect is intended to encompass all such methods known for allowing a pharmaceutically active ingredient to be delivered at least partially through the skin or mucosa.

It would be appreciated that this 20 is typically achieved by applying the composition containing the active ingredient and formulation excipients externally to the surface, i.e. skin, fur, etc. of a subject and allowing sufficient time for absorption through the dermal layers of the subject being treated.

Exemplary methods of administration include pour-on, spot-on, spray, dip, wipe, or other methods apparent to those skilled in the art.

In addition to this, it is contemplated 25 that the transdermal liquid formulation may be incorporated into a transdermal therapeutic system (TTS), such as a patch, as are known in the art.

In one preferred embodiment, the transdermal liquid formulation is suitable or formulated for use as a pour-on preparation.

Typically, "pour-on" formulations are referred to as such because they are poured-on the animal's back, usually from the withers 30 to the tail of an animal, such as cattle, sheep or horses.

The term "therapeutically effective amount' describes a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent.

For example, this can be the amount of the propionic acid-based non-steroidal antiintlammatory agent necessary to reduce, alleviate and/or prevent intlammation and/or WO 2019/113625 - 7 - PCT/AU2018/000255 pain.

In some embodiments, a "therapeutically effective amount" is sufficient to reduce or eliminate a symptom of inflammation and/or pain.

In other embodiments, a "therapeutically effective amount" is an amount sufficient to achieve a desired biological effect, such as an amount that is effective to prevent or decrease redness, heat, swelling, 5 and/or pain associated with inflammation or an inflammatory disease, disorder or condition.

Ideally, a therapeutically effective amount of an agent is an amount sufficient to induce the desired result without causing a substantial cytotoxic effect in the subject.

The effective amount of an agent, such as the propionic acid-based non-steroidal anti- IO inflammatory agent, useful for reducing, alleviating and/or preventing inflammation and/or pain will be dependent on the subject being treated, the type and severity of any associated disease, disorder and/or condition, and the manner of administration of the therapeutic composition.

A therapeutically effective amount of a transdermal liquid formulation comprising 15 the propionic acid-based non-steroidal anti-inflammatory agent may be administered in a single dose, or in several doses, for example daily or every other day, during a course of treatment.

However, the frequency of administration is dependent on the preparation applied, the subject being treated, the severity of inflammation, and the manner of administration of the therapy or composition. 20 In particular embodiments, the amount of the trans dermal liquid formulation to be administered to a subject, including cattle, is from about 0.5 to about 20 mg (e.g., about 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, l 1.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0 mg/kg or any range therein) of the propionic acid-based non- 25 steroidal anti-inflammatory agent (e.g., ketoprofen) per kilogram of body weight of the subject per day or dose.

With respect to cattle, the transdermal liquid formulation is preferably administered to cattle at from about 1 mg to about 5 mg and more preferably about 1.5 mg to about 3.5 mg of the propionic acid-based non-steroidal anti-inflammatory agent (e.g., ketoprofen) per kilogram of body weight. 30 It will be appreciated that propionic acid-based non-steroidal anti-inflammatory agents represent an effective c1ass of non-steroidal anti-inflammatory drugs (NSAIDs) that are structurally derived from propionic acids.

Exemplary propionic acid-based antiinflammatory agents include ketoprofen, alminoprofen, ibuprofen, oxaprozin, zaltoprofen, tiaprofenic acid, naproxen, fenoprofen, flurbiprofen, pranoprofen, dexibuprofen, WO 2019/113625 - 8 - PCT/AU2018/000255 dexketoprofen and loxoprofen, inclusive of pharmaceutically acceptable salts thereof.

In one particularly preferred embodiment, the propionic acid-based non-steroidal antiinflammatory agent is or comprises ketoprofen or a pharmaceutically acceptable salt thereof.

The propionic acid-based non-steroidal anti-inflammatory agent of the transdermal liquid formulation of the invention is suitably to be present in an amount from about 10 mg/mL (i.e., about 1 % w/v) to about 500 mg/mL (i.e., about 50% w/v) or any range therein such as, but not limited to, about 50 mg/mL to about 300 mg/mL, or about 100 mg/mL to about 250 mg/mL.

In particular embodiments of the present invention, the 10 propionic acid-based non-steroidal anti-inflammatory agent is present in an amount of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200,210,220,230,240,250,260,270,280,290,300,310,320,330,340,350,360,370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500 mg/mL or any range therein, of the transdermal liquid formulation.

In certain embodiments of the present 15 invention, the propionic acid-based non-steroidal anti-inflammatory agent is present in an amount from about 100 mg/mL to about 300 mg/mL.

The term "dermal penetration enhancer" is used herein in its broadest sense to refer to an agent or compound which promotes or improves the rate of percutaneous transport of an active agent, such as the propionic acid-based non-steroidal anti- 20 inflammatory agent, across the skin of a subject for systemic or local delivery thereto.

With respect to the dermal penetration enhancer, the alcohol may be any one or more alcohols as are known in the art and may include one or more primary, secondary and/or tertiary alcohols.

More particularly, the alcohol is suitably a primary alcohol, such as methanol, ethanol, propanol, butanol and the like, or a secondary alcohol, such as 25 isopropanol, butan-2-ol and the like.

In one particular embodiment, the alcohol is or comprises ethanol, isopropanol or any combination thereof.

The alcohol of the dermal penetration enhancer is suitably present in an amount from about 10 mL/L (i.e., about 1 % v/v) to about 950 mL/L (i.e., about 95% v/v) or any range therein such as, but not limited to, about 50 to about 700 mL/L, or about 200 to 30 about 500 mL/L.

In particular embodiments of the present invention, the alcohol is present in an amount of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180,190,200,210,220,230,240,250,260,270,280,290,300,310,320, 330,340,350,360,370,380,390,400,410,420,430,440,450,460,470,480,490,500, 510,520,530,540,550,560,570,580,590,600,610,620,630,640,650,660,670,680, WO 2019/113625 - 9 - PCT/AU2018/000255 690,700,710,720,730,740,750,760,770,780,790,800,810,820,830,840,850,860, 870, 880, 890, 900, 910,920,930, 940, 950 mL/L or any range therein, of the transdermal liquid formulation.

In certain embodiments of the present invention, the alcohol is present in an amount from about 100 mL/L to about 600 mL/L.

It will be appreciated that the term "emollient" refers to a chemical agent ( or a mixture of compounds) which increase skin hydration, thereby softening the external layers of the skin.

Emollients may be active (i.e., by delivering water molecules into the skin) or passive (i.e., by reducing and/or preventing water evaporation from the skin).

Additionally, emollients can provide a softening or soothing effect to the skin surface. 10 Emollients can be either solid or liquid at 25°C and may be used individually or as a blend of emollients with melting points above and below 25°C.

The emollient may be any one or more emollients as are known in the art.

Exemplary emollients include fatty acid triglycerides, such as mixtures of caprylic and capric triglycerides (e.g., Crodamo1™ GTCC-LQ, Mig1yo1®, Captex®, Labrafac™ 15 Lipophile WL), palmitic triglyceride, oleic triglyceride, caprylic triglyceride, capric triglyceride, and linoleic triglyceride; fatty acid esters, such as isopropyl myristate, isopropyl palmitate, dibutyl adipate, and dibutyl phthalate; polyhydric alcohols such as propylene glycol, butylene glycol, polyethylene glycol, glycerol, and sorbitol; fatty acids such as lauric, myristic, palmitic, stearic, behenic, o1eic, 1inoleic, lino1enic, lanolic, 20 isostearic, arachidonic and poly unsaturated fatty acids (PUF A); oils such as mineral oil, lanolin oil, coconut oil, cocoa butter, olive oil, jojoba oil, castor oil, silicone oil (such as linear and cyclic polydimethylsiloxanes); higher alcohols, such as lauryl, cetyl, stearyl, oley1, behenyl, cholesterol and 2-hexydecanol alcohol; esters such as cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, 25 isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, glycerol monostearate, glycerol distearate, glycerol tristearate, alkyl lactate, alkyl citrate and alkyl tartrate; cyclomethicone; hydrogenated lanolin; waxes; lecithin, or mixtures thereof.

Suitably, the emollient is selected from the group consisting of a glycol, an unsaturated fatty alcohol, a sorbitol derivative, a myristate, an alkoxylated di-ester of 30 myristyl alcohol and adipic acid, a pyrrolidone, and any combination thereof.

In particular preferred embodiments, the emollient is selected from the group consisting of propylene glycol, oleyl alcohol, dimethyl isosorbide, PPG-3 benzyl ether myristate, di-PPG2- myreth-10-adipate, 1-ethyl-2-pryrrolidone, isomyristate, isopropyl myristate and any WO 2019/113625 - 10- PCT/AU2018/000255 combination thereof.

In alternative embodiments, the emollient (and the alcohol) is not oleyl alcohol.

The emollient of the transderrnal liquid formulation is suitably present in an amount from about 10 rnL/L (i.e., about I% v/v) to about 950 rnL/L (i.e., about 95% v/v) 5 or any range therein such as, but not limited to, about 50 rnL/L to about 700 rnL/L, or about 200 mL/L to about 500 rnL/L.

In particular embodiments of the present invention, the emollient is present in an amount of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300,310,320,330,340,350,360,370,380,390,400,410,420,430,440,450,460,470, 10 480,490,500,510,520,530,540,550,560,570,580,590,600,610,620,630,640,650, 660,670,680,690,700,710,720,730,740,750,760,770,780,790,800,810,820,830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950 rnL/L or any range therein, of the transdermal liquid formulation.

In certain embodiments of the present invention, the emollient is present in an amount from about 100 rnL/L to about 600 rnL/L. 15 As used herein, the term "essential oil" means a volatile oil derived from the leaves, stern, flower or twigs of plants or synthetically-made compounds that have the same chemical attributes.

The essential oil usually carries the odour or flavour of the plant.

Chemically, each plant essential oil or derivative thereof, which may be extracted from natural sources or synthetically made, generally contains, as a major constituent, an 20 acyclic rnonoterpene alcohol or aldehyde, a benzenoid aromatic compound containing at least one oxygenated substituent or side chain, or a monocarbocyclic terpene generally having a six-membered ring bearing one or more oxygenated substituents.

An essential oil also incJudes within its scope derivatives thereof, including racemic mixtures, enantiorners, diastereorners, hydrates, salts, solvates, metabolites, analogs, synthetic 25 derivatives and hornologs.

Non-limiting examples of essential oils include mentha, jasmine, camphor, white cedar, bitter orange peel, ryu, turpentine, cinnamon, bergamot, citrus unshiu, calamus, pine, lavender, bay, clove, hiba, eucalyptus, lemon, starflower, thyme, peppermint, rose, sage, sesame, ginger, basil, juniper, lemon grass, rosemary, rosewood, avocado, grape, 30 grapeseed, myrrh, cucumber, watercress, calendula, elder flower, geranium, linden blossom, amaranth, seaweed, ginko, ginseng, carrot, guarana, tea tree, jojoba, comfrey, oatmeal, cocoa, neroli, vanilla, green tea, penny royal, aloe vera, menthol, cineole, eugenol, citral, citronelle, borneol, linalool, geraniol, evening primrose, camphor, thymol, spirantol, penene, lirnonene and terpenoid oils.

In particular embodiments, the essential WO 2019/113625 - 11 - PCT/AU2018/000255 oil is or comprises menthol, a cineole-based oil, such as eucalyptus oil and/or eucalyptol, or any combination thereof.

In alternative embodiments, the essential oil is not menthol.

The essential oil of the dermal penetration enhancer is suitably present in an amount from about 10 mL/L (i.e., about 1 % v/v) to about 300 mL/L (i.e., about 30% v/v) 5 or any range therein such as, but not limited to, about 20 mL/L to about 250 mL/L, or about 50 mL/L to about 150 mL/L.

In particular embodiments of the present invention, the essential oil is present in an amount of about 10, 20, 30, 40, 50, 60, 70, 80, 90, I 00, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240,250,260, 270, 280, 290, 300 mL/L or any range therein, of the transdermal liquid formulation.

In certain 10 embodiments of the present invention, the essential oil is present in an amount from about 25 mL/L to about 150 mL/L.

The present composition can also optionally include a further pharmaceutically active agent.

It will be appreciated that a wide variety of pharmaceutically active agents can be included with the transdermal liquid formulation described herein, such as a further 15 anti-inflammatory agent (e.g., a further NSAID besides the propionic acid-based nonsteroidal anti-inflammatory agent or a corticosteroid), an anti-microbial, an anthelmintic, a hormone (e.g., synthetic and/or purified), a growth enhancer, an anxiolytic, an antihistamine, an immune stimulant, a vaccine, oxytocin and the like as are known in the art.

Preferably, the further pharmaceutically active agent does not significantly interact 20 with or significantly diminish the activity and/or transdermal absorption of the propionic acid-based non-steroidal anti-inflammatory agent.

In particular embodiments, the transdermal liquid formulation does not further include flunixin or a pharmaceutically acceptable salt thereof.

Other additives or agents can also be added to the present transdermal liquid 25 formulation, as required.

Such agents can include preservatives, chelating agents, antioxidants, buffering agents and viscosity modifying agents.

Exemplary preservatives include without limitation methyl p-hydroxybenzoate (methylparaben) and propyl phydroxybenzoate (propylparaben), added in an appropriate quantity known to one skilled in the art.

Exemplary chelating agents include without limitation edetate disodium and 30 EDT A.

Exemplary antioxidants include without limitation butylated hydroxyanisole, ascorbic acid, and sodium monothioglycerol, added in an appropriate quantity known to one skilled in the art.

Suitable viscosity modifying agents include, without limitation, water, ethanol, isopropanol, propylene glycol, dimethylisosorbide, triacetin, or glycerol, added in an appropriate quantity known to one skilled in the art.

Non.:Hmiting examples of buffering agents include citric acid and maleic acid.

In particular embodiments, the composition further comprises one or more carriers, dilu1.1nw or excipicnts. A useful reference describing pharmaceutically acceptable 5 carriers, diluents and excipients is Remington's Pharmaceutical Sciences (Mack Publishing Co. N.J. U8A1 1991 ).

In one embodiment, the transdermal liquid formulation of the present aspect demonstrates a plasma profile following administration to a subject substantially similar to that observed with an injectable fonnulation of the p;ropionic aci<'.U,ase4 and- 10 inflammatory agent.

To this end, the transdenttal liquid formulation of the present aspect preferably demonstrates a short onset of activity (e.g.,Jess than 10, LS, 20, 25,30, 35, 40, 45, 50; 55 or 60 minutes following administration) so as to facilitate a rapid. reduction in pain, inflammation and/or one or more clinical signs associated therewith.

Additionally, the transdermal liquiq fQrmula:tion of the present aspect preferobly demonstrates 15 substantially cornp1ete cleanu1ce from plasma within,. for example, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18" 19, 20, 21, 22, 23 or 24 hours following administration to a subjec~ and in p.articular cattle, so as to provide minimal withholding periods with respect to milk and/or meat derived from treated animals.

The fonnulation .described herein may be suitable for administration to ariy 20 at1imal, includfng humans ancl non.,.hum~ animals, such as avians inc1usiv.e of p:0ultry (e.g., chickens, ducks, geese, pigeons, quails and turkeys), ruminants (e.g.,. cattle, sheep, goats etc)? pigs, horses, donkeys, dogs and cats.

Iil particular embodiments, the transdermal liquid formulation of the present aspectis for use ln eatt]e.

Accordingly, the transdermal liquid formulation according to the present invention 25 is preferably suitable for the treatmem of pain and/pr an in:flarmnatory di.sease. disQrder or condition in cattle, such as footrot, respiratory disease, acute mastitis, pinkeye (i.e., infectious keratoconjunctivitis), acute pneumonia, metritis and enteritis.

It will be understood that the dosage regimen for treatment of such diseases should be appropriate for the particular inflammatory disease, disorder or condition and the age, weight and sex 30 of the animal to be treated. (n another aspect, the invention provides .a method of preventing and/or treating inflammatic,n in a subject, the method including the step of administering to the subject a therapeutically .effective amount ,of the transdermal liquid formulation of the previous aspect to thereby prevent and/or treat the inflammaiiot1 in the subject.

Date Rer;ue/Date Received 2024-03-26 WO 2019/113625 - 13 - PCT/AU2018/000255 In a related aspect, the invention provides a method of preventing and/or treating pam in a subject, the method including the step of administering to the subject a therapeutically effective amount of the transdermal liquid formulation hereinbefore described to thereby prevent and/or treat the pain in the subject.

In a further related aspect, the invention provides a method of preventing and/or treating lameness and/or loss of mobility in a subject, the method including the step of administering to the subject a therapeutically effective amount of the transdermal liquid formulation of the first aspect to thereby prevent and/or treat the lameness and/or loss of mobility in the subject.

By "reducing", as in reducing inflammation and/or pain in a subject, is meant a lessening or shortening of a symptom, aspect, or characteristic associated with inflammation (e.g., redness, heat, swelling, and/or pain) and/or pain, or of the length of time a subject experiences a symptom, aspect, or characteristic associated with inflammation and/or pain.

Such reducing need not be absolute to be beneficial to the 15 subject.

By "alleviating", as in alleviating inflammation and/or pain in a subject, is meant a reduction in the severity or seriousness of a symptom, aspect, or characteristic associated with inflammation (e.g., redness, heat, swelling, and/or pain) and/or pain.

Such alleviating need not be absolute to be beneficial to the subject.

Reduction and/or alleviation of inflammation and/or pain in a subject can be determined using any methods 20 or standards known to the ordinarily skilled artisan, including both qualitative and quantitative methods and standards, such as those hereinafter described.

It is to be understood that reducing or alleviating inflammation and/or pain in a subject is a method of treating inflammation and/or pain in the subject.

As used herein, "treating" ( or "treat" or "treatment") refers to a therapeutic intervention that ameliorates a 25 sign or symptom of inflammation and/or pain after it has begun to develop.

The term "ameliorating," with reference to inflammation and/or pain, refers to any observable beneficial effect of the treatment.

The beneficial effect can be determined using any methods or standards known to the ordinarily skilled artisan.

As used herein, "preventing" (or "prevent" or "prevention") refers to a course of 30 action (such as administering a therapeutically effective amount of the transdermal liquid formulation provided herein) initiated prior to the onset of a symptom, aspect, or characteristic of inflammation and/or pain so as to prevent or reduce the symptom, aspect, or characteristic.

It is to be understood that such preventing need not be absolute to be beneficial to a subject. A "prophylactic" treatment is a treatment administered to a WO 2019/113625 - 14 - PCT/AU2018/000255 subject who does not exhibit signs of inflammation and/or pain or exhibits only early signs for the purpose of decreasing the risk of developing a symptom, aspect, or characteristic of inflammation and/or pain.

As used herein, "inflammation" refers to the well known localised response to 5 various types of injury or infection, which is characterised by redness, heat, swelling, and pain, and often also including dysfunction or reduced mobility.

Inflammation represents an early defence mechanism to contain an infection and prevent its spread from the initial focus.

Major events in inflammation include dilation of capillaries to increase blood flow, changes in the microvasculature structure, leading to escape of plasma and proteins and 10 leukocytes from the circulation, and leukocyte emigration from the capillaries and accumulation at the site of injury or infection.

As used herein, the term "pain" refers to an unpleasant sensory and emotional experience associated with actual or potential tissue damage caused by or resulting in stimulation of nociceptors in the peripheral nervous system, or by damage to or 15 malfunction of the peripheral or central nervous systems and neural voltage channel transmission.

This term is inclusive of acute and chronic pain, including pain caused by trauma, surgery and/or inflammation.

The term "lameness" as used herein is defined as an abnormal or irregular gait or locomotion characterized by limping or not bearing full weight on one or more 1egs of the 20 subject in question, usually associated with pain in the musculoskeletal system.

More specifically, lameness typically results from the presence of painful lesions on one or more associated bony structures, cartilages, ligaments, synovial membranes, joints or the connective tissue or from an anomaly of local vascularization of the affected leg or legs.

Lameness can manifest itself clinically in an intermittent or continuous manner for several 25 days, several weeks or several months.

Further to this, affected subjects may have reduced activity in standing up and moving including limping, sagging or stiffness and lack of flexion, and adoption of unusual postures.

The term "subject" includes both human and veterinary subjects.

For example, administration to a subject can include administration to a human subject or a veterinary 30 subject.

Preferably, the subject is cattle.

However, therapeutic uses according to the invention may also be applicable to all mammals, such as domestic and companion animals, performance animals such as horses, livestock, and laboratory animals.

By "administer", "administration" and "administering" is intended to describe the introduction or application of the transdermal liquid formulation into or onto a subject by WO 2019/113625 - 15 - PCT/AU2018/000255 a chosen route.

As will be appreciated from the present disclosure, the preferred route of administration is transdermally.

In another aspect, the invention provides a method of administering the transdermal liquid preparation of the first mentioned aspect, including the step of 5 administering a therapeutically effective amount of the transdermal liquid formulation to a subject in need thereof with an application device.

In particular embodiments, the application device is selected from the group consisting of a spray device, a pour-on device, a spot-on device and a transdermal patch.

In one embodiment, the method of the present aspect further includes the initial 10 step of adding the transdermal liquid preparation to the application device.

In another aspect, the invention provides a method of preparing a transdermal liquid formulation, including the steps of: (a) combining a therapeutically effective amount of a propionic acid-based nonsteroidal anti-inflammatory agent and a dermal penetration enhancer comprising an 15 alcohol, an emollient, and an essential oil; and (b) mixing the mixture of step (a) to thereby prepare the transdermal liquid formulation.

For the present aspect, the transdermal liquid formulation is suitably that of the first mentioned aspect. 20 In a particular embodiments of the present aspect, one or more of the dermal penetration enhancers or a portion thereof, are added to a suitable vessel or chamber, followed by the propionic acid-based non-steroidal anti-inflammatory agent and/or any remaining excipients or additives.

The mixture is then mixed until all solids are dissolved.

An additional solvent or surfactant to bring the transdermal liquid formulation to a final 25 volume may be added if needed.

Additives, such as those hereinbefore provided, may also be included in the vessel and mixed into the transdermal liquid formulation.

It will be appreciated that the order of addition of the above dermal penetration enhancers, the propionic acid-based non-steroidal anti-inflammatory agent, excipients, solvents and additives is not critical. 30 In a related aspect, the invention provides a transdermal liquid formulation prepared by the method of the second aspect.

The methods described herein may be applicable to any animal, including humans and non-human animals, such as avians inclusive of poultry (e.g., chickens, ducks, geese, pigeons, quails and turkeys), ruminants (e.g,1 cattle, sheep, goats etc.), pigs, horses~ donkeys, dogs and cats.

Preferably, the subject is bovine.

Throughout the specification the aim has been to describe the preft!:rred embodiments of :the invention without. limiting the invention .to any one embodiment or 5 specific collection of features.

It wilt therefore be appreciated by those of skill in the art that; in light of the instant disclosutf\ various modifications and changes can be made in the particular embodiments exemplified without .departing from the scope of the present invention.

So that the present invention may be n1ore readily understood and put into practical effecti the. skilled person is referred to the following non-limiting examples.

Date Rer;ue/Date Received 2024-03-26 WO 2019/113625 - 17 - PCT/AU2018/000255 EXAMPLE Materials and Methods To confirm transdermal penetration of candidate formulations using in vitro 5 techniques Regional differences in transdermal drug penetration Cattle skin was harvested from Black Angus steers (n = 5, age 1.5 - 2 years, 5/5 body condition score and weighing 508-570 kg).

Hair was removed using an electric clipper 10 and the subcutaneous fat and musculature carefully trimmed away before the skin was cut into circular sections (approximately 2 cm diameter) using a metal wad punch, and placed in airtight ziplock bags, stored at -20 °C within 5 hr of slaughter.

The skin samples were defrosted immediately prior to use and mounted on Franz 15 diffusion cells. A donor solution of radiolabeled lignocaine (Lidocaine [carbonyl-14C] HCI in ethanol, 0. I mCi/mmol; American Radiolabeled Chemicals, St.

Louis, MO, USA) solution was added, while the receptor solution was phosphate-buffered saline containing 4% Bovine serum albumin (Mills et al., 2003, 2005).

The concentration of lignocaine (Cv) was 100 mg/mL, resu1ting in a dose per area of 88.42 mg/cm2. A glass cover slip was 20 applied to each donor chamber to prevent evaporation of the donor solution.

Samples (200 μL) were collected at regular intervals from the receptor chambers via the sampling port and immediately replenished with equal volumes of fresh receptor solution.

At the completion of each study, the diffusions cells were dismantled and the skin discs were rinsed and stored.

Both receptor fluid samples and skin samples were analysed for 25 lignocaine concentration using a Tri-carb® 311 0TR Liquid Scintillation Analyser.

The pseudo-steady state flux Uss or driving force) of lignocaine was derived from the gradient of the regression line through the data points of the linear part of the cumulative amount of lignocaine penetration per skin area against time profile (permeation profile) 30 (Cross et al., 2003b; Mills et al., 2004a).

The time lag or delay before drug first appearing in the receptor fluid (tlag, which correlates to the initial onset of drug activity) was designated as the x-intercept of the regression line (Ahlstrom et al., 2009) and the permeability of active drug in the specific vehicle (kp or permeability coefficient) was WO 2019/113625 - 18 - PCT/AU2018/000255 calculated using the known values of J ss and the concentration of lignocaine hydrochloride in the vehicle (Cv) (Williams, 2003; Ahlstrom et al., 2007) as: k _fss p- Cv The amount of lignocaine in the receptor cell was analysed with respect to length of 5 freezing and sampling time, using factorial ANOVA on STATISTIC™ (version 12; StatSoft Inc., Tulsa, OK, USA).

With respect to the length of freezing, the derived kv and tzag were analysed with repeated measures ANOV A.

The amount of lignocaine retained within the skin each at the end of each experimental was analysed using Kruskal Wallis ANO VA since it had a non-parametric distribution.

Screening of NSAID and vehicle combinations to maximise active drug penetration through cattle skin Four NSAIDs are currently registered for use m Australia: Flunxin meglumine, Ketoprofen, Meloxicam and Tolfenamic acid.

In vitro techniques, as decided in 3.1.1, 15 were used to measure the penetration of each of these four NSAIDs in over 150 vehicle combinations.

The full list of these combinations of active drug and vehicles can be found in Table 13.

Optimising the candidate formulations 20 Once the relative permeability of each NSAID was determined, the most suitable drugvehicle formulation was selected and optimised, in terms of additional excipients and active drug concentration, to enhance transdermal drug penetration.

The terpenes were the most effective from the preliminary studies, but further investigation revealed that eucalyptus oil, also a terpene (containing 1,8 cineole), was even more effective than the 25 Croda-supplied terpenes.

Comparing Eucalyptus oil itself to pure eucalyptol, the complete oil was significantly better at the transfer of ketoprofen through the cattle skin than pure eucalyptol at 5% ( despite the final concentration of I ,8-cineole therefore being lower, which may reflect an addition penetration enhancing effect of eucalyptus oil). 30 Stability studies of the final formulation Preliminary stability studies were performed on the optimal analgesic formulation to ensure no obvious or major concerns with storing the final formulation.

This involved storing the final formulation in glass and plastic (polypropylene) containers at varying WO 2019/113625 - 19 - PCT/AU2018/000255 temperatures (0, 20 and 40°C) for 6 months.

The samples were examined for visual appearance, precipitation and active drug concentration at 0 (when first prepared), 2, 4 and 6 months. 5 Analysis of NSAIDs in biological samples Plasma Protein Precipitation: Cold Acetonitrile (0.2% formic acid) precipitation was added to samples at 1: 1 ratio and vortexed for 30 s.

Protein crashing carried out by 2 rounds of centrifugation for 15min at 20,000 g.

Interval between "crashing" was 30 min at 4 °C.

Supernatant of each sample 10 collected and analysed by LCMS/MS.

Ketoprofen concentration determination by LC-MS/MS (16 March- 28 May 2016) Instrument: Shimadzu Nexera uHPLC in tandem with LCMS 8030.

CID gas: Argon 15 Column: Phenomenex Kinetix C18, 1.7μm pore size.

Mobile phase A: 0.1 % formic acid in water Mobile phase B: 0.1 % formic acid in Acetonitrile LOD: 0.01; QC samples instrument stability (0.1, 2 and 5μg/mL); Calibration range 0.019 - 5μg/mL (similar range to previous experiments in this lab).

Ketoprofen: Test recoveries, using spiked plasma from protein crashing ranged from 91.2 -102.6%.

Detection m/z 255.1 0> 105.20 and confirming ion 255.10>194.25 25 Samples: must be prepared with less than 90% solvent prior to analysis.

Instrument performance and stability: All samples were analysed on the instrument continuously over 4 days. QCs were analysed every 20 samples.

Three sets of calibration curves were assessed. 30 Instrument stability was reasonable.

WO 2019/113625 - 20- PCT/AU2018/000255 Standard CV(%) QCH (5 μg/mL) 9.287 QCM (2 μg/mL) 11.274 QCL (0.1 μg/mL) 10.385 cc 0.0195 μg/mL 14.681 cc 0.0781 μg/mL 10.581 cc 0.3125 μg/mL 14.148 cc 1.25 μg/mL 12.132 cc 5 μg/mL 1.84 To determine the efficacy of candidate transdermal formulations to control pain associated with surgical husbandry formulations Pilot study 1 The study design consisted of a pre-treatment blood sample being collected, then the formulation applied (10 or 40 mL) along the backline between the withers and lumbar region of four calves.

Further blood samples were then collected at 2, 4, 8, 12 and 24 hr 20 later, then analysed for ketoprofen concentrations using UPLC-MS.

The calves were all Droughtmasters (approximately 50% Bos indicus, 50% Bos taurus), as follows: Table 1.

Cattle details for Pilot study 1 Calf ID Gender Weight (kg) Dose volume (ml) (mg/kg) 3405 Male 241 40 3383 Female 191 40 3389 Male 248 10 3385 Female 216 10 Pilot study 2 WO 2019/113625 - 21 - PCT/AU2018/000255 The study design for the second pilot study was the same as the first pilot study, except that all animals received a dose volume of 10 mL.

All calves were estimated to be of similar weight and were from the same cohort of calves as the first experiment.

Body weight was estimated as per industry standard.

The animals were closely observed for any 5 grooming, particularly during the first 2 hr following application.

Blood samples were collected at 0, 1, 2, 3, 4 and 6 hr following application.

Table 2.

Cattle details for Pilot study 2 Calf ID Gender Weight (kg) Dose volume Dose rate (ml) (mg/kg) 3401 Male ~ 220 10 ~g 3415 Female ~ 200 10 ~ 10 3417 female ~ 200 10 ~ 10 3421 Female ~ 200 10 ~ 10 Bioavailability study This was a randomized, non-blinded, crossover pharmacokinetic study.

Cattle (n=14, including two spares) of approximately 250-350 kg body weight were selected from the 15 Y arrandoo herd.

The cattle were randomized to three treatment groups (A, B and C), each of four individuals.

Each group received each treatment once, as described in Table 1.

The treatments were: (1) ketoprofen 3 mg/kg IV (Ilium); (2) ketoprofen 3 mg/kg IM (Ilium); (3) ketoprofen 10 mg/kg topical (transderrnal ketoprofen formulation). A minimum one week 'washout' period was allowed between each treatment.

Cattle 20 receiving the topical treatment were washed, with warm water and shampoo (Fido's Everyday shampoo), applied with a soft brush, and then thoroughly rinsed, 12 hr after application and after all samples had been collected to remove any residual product.

The cattle facilities used for handling of topically-treated animals was appropriately washed after all samples had been collected.

Cattle receiving the IM and IV treatments were 25 handled using facilities separate to any cattle treated with the topical treatment on the same day.

WO 2019/113625 - 22- PCT/AU2018/000255 Blood samples (9 mL) were collected at regular intervals (Table 2).

Blood samples were centrifuged and plasma separated for ketoprofen concentration analysis via UPLC-MS to determine pharmacokinetic parameters.

The pharmacokinetic analysis was performed using Phoenix WinNonLin and a non-compartmental model.

Table 3.

Bioavailability study treatment allocation Treatment Day Ketoprofen Ketoprofen Ketoprofen 3 mg/kg IV 3 mg/kg IM 10 mg/kg topical 0 Al* Bl Cl, C2 pt 1 A2 B2 C3, C4 treatment 2 A3,A4 83,84 - 7 Cl Al - 2nd 8 C2 A2 Bl, 82 treatment 9 C3 A3 B3,B4 10 C4 A4 - 15 Bl Cl Al,A2 3rd 16 B2 C2 A3,A4 treatment 17 B3,B4 C3,C4 *Indicates treatment group and animal (e.g.

Al is animal 1 in Group A) WO 2019/113625 - 23 - PCT/AU2018/000255 Table 4.

Bioavailability study blood sampling times Treatment Blood sampling times (± 1 minute) Ketoprofen 3 mg/kg IV 0, 2, 5, 10, 15, 25, 40 min and 1, 2, 3, 4, 6 and 8 hr Ketoprofen 3 mg/kg IM 0, 10, 20, 30 and 45 min, then 1, 2, 4, 6, 8 and 12 hr Ketoprofen 10 mg/kg 0, 10, 20, 30 and 45 min, then 1, 2, 4, 6, 8 and 12 topical hr For application of the transdermal formulation, the test item was administered topically once to each individual as a single dose at the dose rate of 10 mg/kg (0.05 mL/kg).

Each 5 dose was individually calculated based on the animal's weight, rounded up to the most accurate graduation on the syringe(s).

The test item was equilibrated to ambient temperature prior to administration.

Cattle were dry at the time of treatment and remained dry until the completion of blood 10 collection.

The dose was administered as a pour-on, using a suitably-sized syringe, applied as a single band along the spine between the shoulders and approximately halfway along the back.

Cattle were restrained within a suitable crush at the time of treatment.

Elbow-length gloves, fully enclosed boots and overalls were worn as a minimum during administration.

The animals were observed regularly during the bioavailability study.

Following treatment on day 0 and during the remainder of the working day, the animals were examined regularly for adverse reactions at the time of blood collections.

For animals receiving the topical formulation, the treatment site was specifically examined at 20 approximately 1, 4 and 8 hours post-treatment to ensure no local reactions were evident.

Animals receiving the topical formulation were housed individually until the completion of blood collection on the day of administration and specifically observed for grooming behavior.

During the study, the cattle were inspected at least daily for general health and well-being.

WO 2019/113625 - 24- PCT/AU2018/000255 To develop a formulation containing an NSAID to control pain associated with routine surgical interventions for up to 24 hr Clinical study 5 This study was performed at the Queensland Animal Science Precinct (QASP) at the University of Queensland Gatton Campus.

A total of 36 weaners (male and female - 200 kg, Holstein-Fresian calves) were randomly assigned to one of four groups: (i) Disbudded and placebo transdermal treatment (n=l0). (ii) Disbudded and ketoprofen transdermal (10 mg/kg; n=l0). (iii) Disbudded and ketoprofen intramuscular (3 mg/kg; n=l0). (iv) Sham (handling only) (n=5).

Each group were placed in the holding yard and the treatment applied.

The transdermal ketoprofen or placebo (vehicle only) was applied along the backline, approximately from the shoulder to the mid-point of the backline.

The IM treatment was administered 30 min before the procedure whilst the animals were restrained in a crush.

Once treatment was 20 completed, the animals were moved into the crush (the order of appearance noted for time since treatment) and a blood sample collected.

The husbandry procedure (disbudding) was carried out.

Subsequent blood samples were collected at 0, 1, 2, 4, 8, 24, 48 and 96 hr.

Blood samples were analysed for cortisol and biomarkers once the study was completed. 25 Calf behaviour was monitored before and after dehoming in suitable time periods.

The day before dehorning, the behaviour of all 36 calves were monitored for two hours to record the baseline variation, which was taken as 0 hour observation.

Next day after dehorning, behaviour was recorded at 2-4 hour, 4-8 hour, 8-12 hour, 24 hour and 48 hours.

There were 12 behaviour parameters recorded, as follows: Head shaking, Ear 30 flicking, Tail wagging, Head rubbing, lying, ruminating, neck extending, grooming, walking, vocalising, feeding and drinking.

Each animal was observed for 3 min at each observation period and the frequency of each behaviour parameter during this period was recorded.

This protocol was adapted for Petherick et al (2013), with the subsequent Ethogram used to analyse the behavioural changes during this study.

WO 2019/113625 - 25 - PCT/AU2018/000255 Conventional parameters to assessment pain and inflammation The conventional parameters used to assess pain and inflammation included plasma total cortisol concentration (ELISA using a commercial kit), body weight and the behaviour 5 Ethogram.

Proteomic assessment of pain and inflammation Proteomics is the branch of science that involves identification, quantification and characterization of all proteins in the living individual.

It also plays an indispensable role 10 in assessing the changes in protein expression, occurring in response to various physiological state as well as disease conditions.

In last few years, proteomics has been increasingly used in development of novel biomarkers for early diagnosis of diseases and monitoring of treatment strategies of different diseases in human medicine as well as in veterinary medicine Mass spectrometry (MS) -based proteomics Over the last two decades technological advancement in the field of proteomics has created a lot of opportunities in exploring the complex biological system of living organism.

Especia11y, MS -based techniques have emerged as the most powerful tool to 20 interpret available genomic information and to create quantitative protein profile from plasma, tissues or cell lines of various species.

These techniques also proved useful for analysis of protein-protein interaction, post-translational modifications and gene annotation (Mann and Aebersold, 2003).

Mass spectrometry -based proteomics analysis can be broadly divided into two main domains that include discovery proteomics and 25 targeted proteomics.

The former enables the unbiased identification and quantification of hundreds to thousands of proteins from complex mixtures using shotgun proteomics techniques (explained below), however, in somewhat stochastic manner whereas targeted proteomics focuses only on the subset of selected protein targets important for the biological process under study.

Quantification may be either relative to control sample or 30 on an absolute scale.

Targeted proteomics is more and more commonly employed to validate shotgun proteomics findings and started to replace Western blotting approach.

Shotgun (or discovery) proteomics WO 2019/113625 - 26- PCT/AU2018/000255 Traditionally, proteomics and especially proteomics in veterinary field, has been associated with 2D gels-based approaches. 2D gels, however suffer from several issues such as lack of reproducibility, being laborious, underrepresentation of certain classes of proteins and most importantly each protein spot in fact consists of multiple proteins.

The 5 idea of shotgun proteomics was introduced in order to avoid having to do 2D gels.

Shotgun proteomics is one of the most widely used approaches for identification and/or quantification of maximal number of proteins in a given samples.

It has achieved high throughput analysis as compared to other conventional MS-based techniques because of advantages associated with it.

First is proteolytic digestion of proteins into short peptides 10 followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based sequencing, simplifies the sample handling and increase its efficiency of protein identification (Nesvizhskii and Aebersold, 2005).

In shotgun proteomics, proteins are denatured, cysteine residues alkylated and the proteins digested into peptides.

Various fractionation strategies can be introduced at the protein or peptide level.

These peptides 15 are then desalted and analysed by liquid chromatography tandem mass spectrometry (LCMS/ MS) in data dependent acquisition mode (explained below).

The most frequently used instruments for shotgun proteomics include ion-trap, hybrid ion-trap/orbitrap, hybrid quadrupole/orbitrap and hybrid quadrupole/TOP mass spectrometer.

However, spectra obtained in all these methods vary with regard to their quality (resolution and mass 20 accuracy).

There are several other DDA-based quantitative proteomics strategies (label free and label-based, the most popular being spectral counting, SILAC, TMT tags, iTRAQ tags).

Application in veterinary science 25 Shotgun proteomics techniques support formulation of new hypotheses and are ideally suited for discovery studies due to theirs high sensitivity and ability to screen hundreds to thousands of proteins at once.

Its use has been increased in veterinary medicine in the last few years especially in farm animals.

Either plasma or other body fluids or tissues have been utilized with a various degree of success.

Shotgun analysis has 30 been conducted on plasma samples from dairy cattle suffering with foot rot, to understand plasma protein profile and to discover potential disease-associated proteins.

Plasma proteins were separated by SDS-PAGE and finally LC-MS/MS was performed. A total of 648 proteins were identified in healthy plasma samples, of which 234 were non-redundant proteins and 123 were high-confidence proteins; and 712 proteins were identified from WO 2019/113625 - 27 - PCT/AU2018/000255 infected animal plasma, of which 272 were non-redundant proteins and 138 were highconfidence proteins (Sun et al., 2013).

Another study has conducted comparison of the bovine uterine flushing (UF) and plasma proteome using iTRAQ labelling and SCX separation of the iTRAQ labelled peptides and finally LC-MS/MS technique have enabled 5 identification of 53 proteins, out of that 35 proteins were higher in UF compared to plasma (Faulkner et al., 2012).

Serum proteome has analysed from normal and FMD virus infected piglets using LC-MS/MS after removing high abundance proteins with depletion kit.

In control group, 8 proteins were identified while in virus infected piglets total 9 proteins were identified with good reproducibility and 3 proteins appeared after FMD 10 infection which were absent in healthy (control) animal (Liu et al., 2011).

In one study of swine, serum proteomic analysis was done using shotgun (LC-MS/MS) approach after depleting high abundance proteins using SepproTip columns. A total of 1,096 proteins were identified and quantified, of which 182 were identified with multiple unique amino acid sequences and high peptide ID confidence (Bell et al., 2010).

Finally, data dependent 15 acquisition is critical for spectral library collection used for deconvolution of SWATH data.

Results 20 To confirm transdermal penetration of candidate formulations using in vitro techniques Regional differences in transdermal drug penetration In all animals, the cumulative amount of 1ignocaine hydrochloride penetrating through skin significantly increased over time (P < 0.001) (see Figure 1).

There was a significantly 25 higher cumulative amount of lignocaine penetrating through the skin from animals 2 and 4, compared to animals 1 and 3 (P < 0.001).

From a pair-wise comparison, the amount of lignocaine penetrating through the skin in animal 5 did not significantly differ from other animal (P > 0.1), except animal 1 (P < 0.05) 30 There were significant differences in the cumulative amount of lignocaine that penetrated through all the skin regions (P < 0.001) (See Figure 2), with the thorax significantly higher than the other three regions (P < 0.001).

The amount of lignocaine penetrated through the scrotal skin was also significantly higher than the skin from the dorsal midline (P < 0.001) and ventral abdomen (P < 0.001).

After 24 hr exposure, the concentration of WO 2019/113625 - 28 - PCT/AU2018/000255 lignocaine hydrochloride retained within the scrotal skin was significantly higher than the other regions (P < 0.001) (See Figure 3).

The concentrations of lignocaine in the skin from the ventral abdomen, dorsal midline and thorax did not significantly differ (P > 0.5). 5 Screening of NSAID and vehicle combinations to maximise active drug penetration through cattle skin Over 150 vehicle combinations were screened in this study.

Of the four NSAIDS registered for use in cattle in Australia, tlunixin appeared to be the most soluble in the majority of vehicles examined. A number of these vehicles were quite effective in moving 10 tlunixin through cattle skin in vitro, particularly combinations of ethanol, propylene glycol and eucalyptus oil, which were more effective than 100% eucalyptus oil.

However, there was significantly more ketoprofen penetrating through cattle skin in all of the vehicles used in this study (Figure 4).

Both tolfenamic acid and meloxicam were not particularly soluble in most of the vehicles tested and both drugs also had little to no 15 penetration through cattle skin. A full list of the vehicles and raw data can be found in Table 13.

Optimising the candidate formulations Once it was decided to move forward with ketoprofen, the vehicles were refined to 20 maximise transdermal drug penetration. A combination of alcohol and eucalyptus oil provided the most favourable transdermal drug movement.

Ethanol (50-70%) was stable and significantly enhanced penetration compared to other alcohols (Figure 5).

Isopropanol was included in the range of alcohols tested, since it is commonly used in other topical formulations and was considered a safer (less flammable) option.

However, 25 isopropanol did not transfer NSAIDs well for any of the actives tested and did not perform as well as ethanol.

Several solubilising agents were tested, including propylene glycol (PG), oleyl alcohol and isopropyl myristate (1PM), with 1PM proving the more effective (Figure 6). A final combination of 50: 50 ethanol and 1PM, mixed with 10% eucalyptus oil (~7% 1,8-cineole), meaning that ethanol and IPM are actually at 45% each. 30 A range of active concentrations (10, 20 and 30%) were also considered.

Ketoprofen at 30% did result in mild precipitation at room temperature, while 20% seemed quite stable, so was selected as the ideal concentration (Figure 7).

Stability studies of the final formulation WO 2019/113625 - 29- PCT/AU2018/000255 There was no change in the final formulation at 2 or 4 months storage, in terms of precipitation, crystallisations, colour and evaporation.

There was some evidence of evaporation, particularly from the glass vessels, most noticeably in samples containing higher ethanol components (50% and 70%) when stored at 40°C, particularly those with 5 appeared to have evaporated quicker than the others from the glass vessels.

At 6 months, evaporation wa'i evident in all samples stored in glass at 40 °C and some at ambient temperature. A small colour change was observed in samples stored at 40 °C. 10 Concentration of ketoprofen remained stable (20 ± 1%) throughout, although small amounts of ketoprofen methyl ester were detected in some samples stored at 20 and 40 °C (see Figure 8).

Analysis of ketoprof en in biological samples 15 Plasma Protein Precipitation: Cold Acetonitrile (0.2% formic acid) precipitation was added to samples at 1: 1 ratio and vortexed for 30 s.

Protein crashing carried out by 2 rounds of centrifugation for 15min at 20,000 g.

Interval between "crashing" was 30 min at 4 °C.

Supernatant of each sample 20 collected and analysed by LCMS/MS.

It is noted that further cleaning and processing of samples will enable better sensitivity to the assessment.

For the purpose of continuity method of sample preparation was not changed throughout the project.

Ketoprofen concentration determination by LC-MS/MS (9-12th Jan 2017) Instrument: Shimadzu Nexera uHPLC in tandem with LCMS 8030.

CID gas: Argon Column: Phenomenex Kinetix Evo C18, 1.7μm pore size. 30 Mobile phase A: 0.1 % formic acid in water Mobile phase B: 0.1 % formic acid in Acetonitrile LOD: 2 ppb; QC samples instrument stability at 0.02 μg/mL; Calibration range 0.0049 - 5μg/mL.

WO 2019/113625 - 30 - PCT/AU2018/000255 Ketoprofen: 255.10>209.30 Detection m/z 255.10>105.20 and confirming ion 255.10>194.25, Collision energies for each transition was optimised Co-elution of all peaks are checked and verified in all analysis files.

The right chart verifies the retention time %CV of each 5 transition across all files.

ISTD Ibuprofen: Unsuccessful - instrument negative ion mode wa<; out of order and the column length was likely to be too short, and a longer chromatography programme may have been required.

Current modifications to be considered is the use of deuterated 10 ketoprofen or another surrogate NSAID to be used as an ISTD.

Samples: must be prepared with less than 90% solvent prior to analysis.

Instrument performance and stability: All samples were analysed on the instrument 15 continuously. QC was analysed every 20 samples, CV <5%.

Five sets of calibration curves were assessed.

Calibration curve and retention time of variation: Figure 9 below illustrates a proportion of the standards Figure 11 shows QC data alignment of the retention times of Ketoprofen 20 during the analyses.

To determine the efficacy of candidate transdermal formulations to control pain associated with surgical husbandry formulations 25 Pilot study 1 The plasma ketoprofen concentrations (~tg/mL) in each calf were as follows: Time (hr) Calf 3405 Calf 3383 Calf 3389 Calf 3385 0 0.057 0.021 0.027 0.024 2 12.21 42.768 1.905 3.498 4 1.092 2.103 3.132 0.963 8 0.603 0.252 1.503 0.048 12 0.375 0.102 0.303 0.108 WO 2019/113625 - 31 - PCT/AU2018/000255 124 1 o.075 1 o.045 1 0.111 1 o.285 Plasma ketoprofen concentrations were detectable and approached what may have been expected following IM administration.

The lag time (between application and appearance of active in the plasma) was unexpectedly very short (most transdermal formulations 5 exhibit a lag time of several hours).

It was uncertain if the peaks for the applications had been missed.

It was also unsure if any grooming had contributed to the short lag time but casual observation indicated this was unlikely to have been significant.

Pilot study 2 10 The plasma ketoprofen concentrations (μg/mL) were as follows: Time (hr) Calf 3401 Calf 3415 Calf 3417 Calf 3421 0 0.021 0.039 0.258 0.321 1 2.301 0.405 0.192 0.048 2 2.904 5.199 6.624 9.912 3 1.965 2.616 4.182 8.103 4 1.251 0.711 1.314 2.616 6 0.951 0.426 0.744 0.933 There was no grooming observed at any stage during the second pilot study.

Again, a short lag phase was observed, with peak plasma concentrations ~ 2 hr following 15 application.

Although we did not weigh the calves, there did seem to be a weight-related effect, since the lowest plasma concentrations were in calf 3401 and the highest in calf 3421, which were estimated to be the heaviest and lightest calves, respectively, although calf 3401 was male and there may be some gender differences. 20 Bioavailability study The PK results can be seen below in Figures 14 and 15, and Table 5.

The transdermal formulation had a slower absorption than IM, although the peaks were equivalent at 30 minutes. A peak (CMAx) occurred~ 2 hr. A bioavailability of 50% and an area under the curve (AUC; 3940 μg.mL/min) exceeding that following IM administration (2376 WO 2019/113625 - 32- PCT/AU2018/000255 μg.mL/min) suggested that the transdermal formulation had a greater systemic effect than IM administration.

Unfortunately, evidence of skin irritation was observed several days after administration 5 of the transdermal formulation, continuing to marked skin inflammation and excoriation in the 3-4 weeks following application (Figure 16).

It was uncertain if this irritation was due to photosensitisation of the ketoprofen, the fact that the transdermal formulation had been administered three times to each animal or other environmental factors. 10 Table 5.

The pharmacokinetic (Pk) parameters for ketoprofen administered to cattle by IV, IM and transdermal routes Dose Cmax Cmax AUC 0-AUC Half-life (mg/kg) /Co /dose Tmax Last Inf/dose (ruins) F (%) IV 3 77 22 NA 2363 806 121 IM 3 11 4 74 2376 856 164 101 Topical 10 20 2 115 3940 404 155 50 To develop a formulation containing an NSAID to control pain associated with routine surgical interventions for up to 24 hr Clinical study This study was successfully performed and all 36 animals completed the study.

Some calves required attention to continued bleeding from the dehorning site, which was 20 undertaken manually.

All animals remained in good health throughout the study.

Conventional parameters to assessment pain and inflammation Total cortisol 25 The total plasma cortisol concentration (ng/rnL) in each animal at each time point can be observed in table 6.

WO 2019/113625 - 33 - PCT/AU2018/000255 Table 6.

Total plasma cortisol concentration (ng/mL) Time Group Animal 0 1 2 4 8 24 96 Placebo50 3.5 18.2 8.2 27.7 4.0 5.6 16.1 Placebo54 10.0 19.2 36.9 32.6 24.1 19.5 22.5 Placebo60 6.4 36.6 21.4 30.0 19.8 12.9 25.7 Placebo61 2.0 17.2 21.8 24.9 21.1 24.6 7.5 10 Placebo68 13.7 13.1 19.2 21.8 18.8 11.8 9.3 Placebo76 8.4 28.4 35.7 31.8 22.9 37.8 25.6 Placebo74 16.8 29.7 24.6 34.9 37.1 30.8 19.3 Placebo47 15.9 30.9 9.6 15.5 15.8 20.1 8.7 Placebo44 19.0 24.2 17.6 39.9 41.9 14.6 4.8 15 Placebo52 6.8 8.1 46.6 8.8 5.6 7.0 6.0 mean 10.2 22.5 24.2 26.8 21.1 18.5 14.5 SEM 1.8 2.8 3.9 3.0 3.7 3.3 2.6 TransD 72 6.5 4.6 3.9 14.5 10.4 1.9 1.9 20 TransD 78 4.0 6.6 1.9 4.2 Missing 1.9 10.9 TransD 75 8.8 1.9 1.9 14.7 16.6 21.9 2.7 TransD 64 1.9 28.0 2.6 6.0 19.9 2.7 19.1 TransD 48 3.2 27.5 13.4 3.1 17.0 1.9 16.7 TransD 67 1.9 Missing 4.8 22.1 14.2 16.5 9.9 25 TransD 39 8.0 16.5 4.8 9.0 11.4 12.7 9.9 TransD 51 8.4 16.3 6.1 1.9 13.3 9.1 9.4 TransD 46 Missing 4.0 1.9 1.9 22.8 1.9 2.3 TransD 43 2.4 29.1 10.7 19.0 28.7 6.8 16.8 mean 5.0 15.0 5.2 9.7 17.1 7.7 9.9 30 SEM 1.0 3.7 1.2 2.4 2.0 2.3 2.0 Sham 69 1.9 1.9 8.5 5.4 10.1 14.0 8.2 Sham 58 2.7 8.9 5.6 2.4 7.7 1.9 17.1 Sham 66 1.9 2.9 1.9 7.0 12.8 4.5 6.7 35 Sham 49 5.1 12.1 2.4 1.9 19.5 3.8 2.6 Sham 53 1.9 2.3 1.9 11.3 16.4 1.9 1.9 Sham 38 1.9 1.9 2.2 1.9 1.9 1.9 Missing mean 2.6 5.0 3.7 5.0 11.4 4.7 7.3 SEM 0.5 1.8 1.1 1.5 2.6 1.9 2.7 IM 82 2.9 3.3 4.1 29.9 23.3 21.9 30.0 IM 77 3.2 7.9 4.4 24.6 20.9 10.6 4.5 IM 65 7.8 5.9 9.0 15.8 18.9 6.7 26.9 IM 70 6.1 3.4 3.7 25.2 8.6 1.9 8.3 45 IM 56 11.8 13.5 4.6 16.2 12.9 6.9 30.7 IM 63 3.1 7.1 8.1 8.3 10.3 16.7 11.7 IM 35 13.0 30.8 6.4 19.7 28.8 6.5 2.3 IM 42 2.8 42.6 39.1 19.2 10.7 9.6 16.6 IM 40 3.7 7.6 10.1 4.4 7.9 2.8 4.1 50 IM 55 4.0 6.1 15.5 6.3 18.8 22.5 16.7 WO 2019/113625 mean 5.8 SEM 1.2 - 34- PCT/AU2018/000255 12.8 10.5 17 .o 16.1 10.6 15.2 4.2 3.4 2.7 2.2 2.3 3.4 5 When looked at graphically, it can be seen that there are differences between the groups when looked at over the entire 96 hr (Fig 17) and, particularly, during the first 4 hr (Fig 18).

The most obvious differences are in the first 4 hr.

At 8 hr all treatments had an increase 10 and there was no treatment effect post 8 hr.

An ANOV A on each time point and the statistical result is shown on the 4 hr (Fig 18).

At the start (time 0) the placebo were slightly higher than others, while placebo increased markedly over time being significant from sham at all time points up to 4 hr. 15 The IM and Trans D increased from time 0 and were essentially the same (not different from each other at any time point).

At l hr the Trans D and IM were not different from either sham or placebo (i.e.

Intermediate).

But at 2 hr both the Trans D and IM were not different from sham, but they were obviously both lower than placebo.

At 4 hr the IM increases a bit to become significant from sham, but not Trans D.

These results mean that there was no difference in cortisol concentration between Trans D, sham OR IM at any time point.

In Trans D there was a mild NS increase in cortisol at 1 hr compared to sham.

There was a significant blunting of the stress response by transD and IM and 1, 2 and 4 hr post dehorning.

The increase in cortisol at 8 hr for the sham 25 group may reflect apprehension at repeated sampling.

Bodyweight There were no significant differences between either treatment group and the sham group, 30 while both IM and transdermal groups had significantly (P<0.05) higher body weight gain, compared to the placebo group.

WO 2019/113625 - 35 - PCT/AU2018/000255 Table 7.

Body weight changes in dehorned calves compared to sham-treated calves, compared to the effects of ketoprofen, administered IM or transdermally Treatment Body weight Animal no.

Animal ID 26/10/2016 10/11/2016 1/12/2016 1 74 89 118 143 2 76 99 125 153 3 68 115 142 160 4 61 135 165 201 5 60 150 169 212 Placebo (Y) 6 54 161 186 190 7 50 l 77 211 238 8 47 188 205 246 9 44 191 205 249 10 52 212 233 266 Mean 151.7 175.9 205.8 SD 41.6 38.8 43.8 11 72 92 112 132 12 78 98 118 145 13 75 112 139 171 14 64 127 155 184 15 48 150 180 211 Keto TD 16 67 165 195 225 (R) 17 39 176 213 246 18 51 180 206 241 19 46 205 242 281 20 43 215 252 292 Mean 151.9 181.2 212.8 SD 43.5 49.2 54.4 Keto IM 21 82 93 107 135 (B) 22 77 94 120 152 WO 2019/113625 - 36 - PCT/AU2018/000255 23 65 110 141 164 24 70 116 134 169 25 56 150 179 207 26 63 156 187 224 27 35 191 210 252 28 42 191 216 257 29 40 205 240 278 30 55 212 250 287 Mean 151.8 178.4 212.5 SD 46.4 50.9 55.2 31 69 104 126 148 32 58 107 126 162 33 66 145 172 208 Sham 34 49 149 183 215 control (G) 35 53 184 216 246 36 38 236 264 311 Mean 154.16 181.16 215 SD 49.9 53.4 59.2 Behaviour Ethogram and analysis The initial challenge was to determine which variables were indicators of pain and these 5 could then be further investigated and compared between groups.

The method used to identify those variables was Confirmatory Factor Analysis (CF A) within Structural Equation Modelling Framework (SEM).

This method is far more superior to Principal Component Analysis (PCA), Multiple Component Analysis (MCA) or Factorial Analysis (FA) because it permits the use of information from all the variables in the dataset to 10 describe which ones are better predictors of another latent variable, in this case, Pain.

SEM is a conceptual map and hypothesis-driven process.

Relationships between predictor variables (sems language 'observed variables') have to be plausible for SEM to produce WO 2019/113625 - 37 - PCT/AU2018/000255 reliable estimates that describe the relationship between the observed variable and the latent variable outcome.

The model output below describe the final, and most stable, models fitted using sems 5 function in STATA 13.

Only statistically significant variables remain (P<0.05) in the final model.

The conceptual framework of the model is also plotted to make the interpretation of model outcome more accessible to the reader.

In the conceptual model map (Figure 19), the oval shape is the latent variable (Pain). 10 Square shapes are the observed variables.

The circles are the standard error terms of each of our variables.

The arrows are pathways between the latent variable and observed variables and between the error terms of the observed variables (i.e. allows for those variables to correlate with each other).

The values shown on those arrows are the values estimated from the sem model (variable loading).

Those values are standardised across the 15 entire model, and they are used quantify the association between the latent and observed variables.

They are interpreted roughly like regression coefficients as a function of standard deviation change in the latent and observed variables.

Seven variables (Ear flick, tail wag, ruminating, head shake, lying, grooming and neck 20 extending) had substantial loading and were statistically significant.

The interpretation is as follow: if an animal is One Standard Deviation higher in Pain (or pain score), it will have/score 0.78 Standard Deviation (SD) higher (positive coefficient) Ear flick count, 0.66 SD higher in Tail wag, 0.36 SD lower (negative coefficient) in Rumination and 0.25 SD lower in Grooming.

You can also not ignore the negative correlation between tail 25 wagging and laying down, or that between earflick and headrub.

This confirms that the model framework is sound and reliable.

These observed variables can then be compared over time and between groups using separate Poisson models.

Ideally (i.e. to demonstrate efficacy), there would be lower 30 counts of positively correlated variables with pain and higher counts of those variables negatively correlated with pain.

Fitting Mixed effect Poisson and negative binomial models WO 2019/113625 - 38 - PCT/AU2018/000255 Separate models were used for each of the observed animal behavioural traits (Figure 19).

A mixed effect Poisson model with an animal fitted as random intercepts and time as random slope, and unstructured error term for the residuals.

Behaviours trait at baseline (time 0) was centred and added to the fixed effect part of the model ( essentially turning 5 the model into a random slope model too).

Overdispersion was assessed and it was ruled out as being problematic (the scale is ~ 1 and not significant.

Overdispersion was not an issue).

Overdispersed models (also those with excess zeros) were refitted using a negative binomial model.

Poisson: ear flick, tail wag and Negative binomial: headshake, head rub, lying, ruminate, neck extend, grooming.

Experimental time was fitted as a categorical variable to derive estimated at each time point, time 2 hr was used as the reference category.

Treatment was also fitted as categorical variable, placebo as reference category.

Two-way interaction with Treatment was forced and remained in the final model.

The interpretation of the coefficients in Table 15 1 below is as follows: The coefficient for Keto Trans (compared with Placebo) is -0.03, which means that, on average, the expected log ear flick count in Keto Trans was reduced by 3%, compared with Placebo group.

This is equivalent to, on average, the incident risk ( count) of Head 20 Rub Count (IR) for Keto Trans was 0.97 times that of the Placebo group (Incidence Risk/count Ratio =IRR).

Similarly, the highest incidence risk (count risk) of head rub was observed 4 hr after exposure, compared with the reference time (2 hr).

Unfortunately, none of the treatment groups main effect were statistically significant. 25 The true treatment effect is estimated using the interaction term.

Hence, it was forced in the final models.

In the marginal tables below (Tables 7-10) and Figure 20, the interaction term was not significant either.

The same comments about the main effect apply here too.

Although no statistical differences were observed, there are numerical differences in favour of treatment.

The lack of statistical differences is related to the lack of statistical power in this study.

To clarify, assuming a power of 80%, significance level percentage of 95%, balanced groups size, a probability of observing an outcome in the control group of 80%, the required WO 2019/113625 - 39- PCT/AU2018/000255 sample size for this study to detect an odd ratio ( or IRR) of 4 or greater is 88 animals in each group.

The current study has a power of 17%. en C cr !!l. e ro en :::, (I) !2. ;a C 1D N 0) ~ ► C Table 8.

Marginal table for head rub, head shake and ear flick Animal Behaviour Variable Head rub Coef (SE) IRR95%CI Constant -3.75 0.02 {0.00 to (0.98) 0.16) Behaviour's count at Baseline 0.96 {0.93) 2.61 {0.42 to (time0) 16.00) Time 2h Reference 4h -1.84 0.16 {0.07 to {0.44) 0.38) 8h -3.64 0.03 (0.00 to {1.01) 0.19) 24hrs -2.14 0.12 {0.00 to (2.95) 38.00) 48hrs -1.99 0.14 {0.04 to (0.62) 0.46) Treatment Placebo Reference Keto Trans -0.03 0.97 (0.37 to (0.49) 2.55) Keto IM -0.77 0.46 (0.12 to (0.70) 1.83) p <0.01 0.30 <0.01 <0.01 0.21 <0.01 0.96 0.27 Head shake Coef(SE) IRR95% Cl p Coef(SE) -3.12 0.04 {0.02 to <0.01 -3.37 (0.36) 0.09) (0.17) -0.32 0. 72 {0.26 to 0.53 -0.05 {0.52) 2.02) (0.04) Reference -0.32 0. 72 {0.26 to 0.53 -0.04 (0.52) 2.02) (0.17) -1.17 0.31 (0.10 to 0.04 -0.36 {0.58) 0.97) (0.18) -2.27 0.10 (0.02 to <0.01 -1.73 (0.75) 0.45) (0.30) -2.67 0.07 (0.01 to <0.01 -1.35 (0.85) 0.37) (0.26) Reference -1.22 0.30 (0.11 to 0.02 -0.07 {0.51) 0.81) (0.18) -0.12 0.89 (0.32 to 0.82 -0.10 (0.52) 2.45) (0.19) Ear Flick IRR 95%CI p 0.03 (0.02 to <0.01 0.05) 0.95 (0.87 to 0.22 1.03) 0.96 (0.69 to 0.80 1.33) 0.70 (0.49 to 0.05 1.00) 0.18 (0.10 to <0.01 0.32) 0.26 (0.16 to <0.01 0.43) 0.93 (0.65 to 0.68 1.32) 0.91 (0.62 to 0.60 1.32) .. 0 ~ N .0.. . ~........ w 0'I N Ul ""d (") '"3 s;;: ~ N .0.. . ~ 0 N Ul Ul ~ 0 "' 0 ."u.'., ""'' "' 0 "' 0 I 0 "' ,,..I .. en C cr !!l. e ro en :::, (I) !2. ;a C 1D N 0) ~ ► C Table 9.

Marginal table for tail wag, lying and neck extending Animal Behaviour Variable Tail wag Coef(SE) IRR95% Cl Constant -3.13 0.04 (0.03 to (0.18) 0.06) Behaviour's count at Baseline -0.12 0.88 {0.79 to (time0) (0.06) 0.99) Time 2 hr Reference 4h -0.37 0.69 (0.44 to (0.23) 1.07) 8hr -0.88 0.42 (0.25 to (0.27) 0.70) 24 hr -1.39 0.25 (0.13 to (0.32) 0.47) 48 hr -1.16 0.31 (0.18 to (0.30) 0.56) Treatment Placebo Reference Keto Trans -0.22 0.80 (0.52 to (0.22) 1.24) Keto IM -0.08 0.92 {0.60 to {0.22) 1.41) p <0.01 0.03 0.09 <0.01 <0.01 <0.01 0.32 0.71 Lying Coef(SE) IRR95%CI p Coef(SE) -2.62 0.07 (0.03 to <0.01 -2.42 (0.45) 0.18) {0.17) -0.51 0.60 {0.31 to 0.13 -0.58 (0.34) 1.16) (0.28) Reference Reference -0.62 0.54 (0.21 to 0.18 -0.58 (0.47) 1.35) {0.28) -0.77 0.46 (0.18 to 0.11 -0.83 (0.49) 1.21) (0.31) -2.56 0.08 (0.01 to 0.01 -1.16 (1.04) 0.59) (0.34) -2.56 0.08 (0.01 to 0.01 -1.16 (1.04) 0.59) {0.37) Reference Reference -0.74 0.48 {0.15 to 0.20 -0.07 (0.58) 1.49) (0.26) -0.61 0.54 (0.19 to 0.25 0.05 (0.30) (0.53) 1.53) Neck extended IRR95%CI p 0.09 (0.06 to <0.01 0.12) 0.56 (0.33 to 0.03 0.97) 0.56 (0.33 to 0.04 0.97) 0.44 {0.24 to <0.01 0.81) 0.31 (0.16 to <0.01 0.61) 0.31 (0.15 to <0.01 0.64) 0.93 (0.55 to 0.78 1.56) 1.05 {0.59 to 0.85 1.88) .. ""' ~ N 0 ""' ~ w""""'' 0'I N Ul ""d (") '"3 s;;: ~ N 0 ""' ~ 0 N Ul Ul ~ 0 "' 0 ."u.'., ""'' "' 0 "' 0 I 0 "' ,,..I ..

Table 10.

Marginal table for grooming and ruminating Animal Behaviour ~ Variable Grooming Ruminating 0 N Coef(SE} IRR95% Cl p Coef(SE} IRR95% Cl p ,0. . 1,0 Constant -7.15 (1.42) 0.00 (0.00 to 0.01) <0.01 -11.17 (3.19) 0.00 (0.00 to 0.01) <0.01 -,,....

Behaviour count at Baseline (time 0) 0.09 (0.26) 1.10 (0.67 to 1.82) 0.71 -0.08 (0.43) 0.93 (0.40 to 2.16) 0.86 w 0'I N Time (continuous variable} 0.66 (0.32) 1.94 (1.04 to 3.62) 0.03 2.11 (1.06) 8.22 (1.03 to 65.45) 0.04 Ul Treatment Placebo Reference Keto Trans 0.08 (2.12) 1.08 (0.02 to 68.22) 0.97 0.64 (0.77) 1.91 (0.42 to 8.65) 0.40 Keto IM 0.90 (1.78) 2.46 (0.08 to 80.6) 0.61 -0.30 (1.10) 0.74 (0.09 to 6.37) 0.78 (J) Table 11.

Predicted marginal means from derived from the models above for an animal with behavioural count at baseline set to the average observed ,:: 0- !!?. for that trait. e= ~ ro Time 0 (J) "0 ' ::, Behaviou 2 hr 4 hr Shrs 24 hr 48 hr "' (I) .u.., S?.

Placeb KteoTra Ketol Placeb KteoTra Ketol Placeb KteoTra Ketol Placeb KteoTra Ketol Placeb KteoTra Ketol r ,i;... "' ;a N "' ,:: "' 0 ns M 0 ns M 0 ns M 0 ns M 0 ns M 0 1D "' 0 N Head rub 6.17 6.00 2.85 0.98 0.95 0.45 0.16 0.16 0.08 0.00 0.00 0.00 0.84 0.82 0.39 I ;0u) "' I Head ,.. 0 ,.. ► shake 4.44 1.32 3.94 3.21 0.70 3.42 1.38 0.47 1.20 0.46 0.42 1.03 0.31 7.09 0.17 C Ear flick 2.02 1.88 1.83 1.94 1.97 2.09 1.41 1.34 1.26 0.36 0.49 0.43 0.53 0.52 0.50 Tail wag 1.29 1.04 1.19 0.89 0.92 0.95 0.54 0.69 0.63 0.32 0.40 0.30 0.40 0.37 0.42 Laying 4.60 2.87 2.91 2.47 2.18 2.22 1.33 1.66 1.69 0.72 1.27 1.29 0.39 0.96 0.98 Neck 0.98 0.91 1.03 0.55 0.76 1.31 0.43 0.46 0.69 0.31 0.38 0.69 0.31 0.42 0.69 extended Groomin "'d 0.19 0.21 0.34 0.36 0.42 0.50 0.70 0.84 0.73 1.36 1.68 1.07 2.63 3.39 1.56 ("') .-3 g s; Ruminati ~ 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.02 0.02 0.02 0.18 0.15 0.15 N 0 ng ,.. -QC 0 N Ul Ul WO 2019/113625 - 43 - PCT I AU2018/000255 Proteomic assessment of pain and inflammation Currently, data collection to create an expanded cattle plasma spectral library is in progress.

Plasma samples from a wide range of animals (age, breed/species and health 5 conditions) are being interrogated in order to identify as many plasma proteins as possible.

Spectral library construction is an inevitable component of SW ATll-MS analysis.

This analysis uses information contain in a library to analyse the acquired fragment ion maps to identify and quantify the targeted peptides because all the information about fragment ion signals, their intensities and chromatographic concurrence 10 of targeted peptide can be access from this library.

If the targeted peptide is not present in the spectral library then it cannot be identified and quantified in SWATH-MS analysis of samples.

We have processed eight plasma samples from adult cattle suffering with different pathological conditions.

Sample preparation was done using in solution digestion method. 15 Desalting was performed using stage tips.

After sample preparation, mass spectrometer analysis was conducted using LC-MS/MS technique on ABSciex platform.

Data generated through mass spectrometer were analysed using ProteinPilot search engine against bovine protein database.

Data were analysed at 1 % global FDR to eliminate falsely discovered proteins.

We also removed proteins with very low unused score and 20 very low peptide number to avoid false positive results.

Currently, approximately 165 proteins, including immunoglobulins, have been identified from all of these samples.

Table 1 shows proteins of interest that include acute phase proteins, oxidative stress marker and few highly abundant cytokines.

This list will be expanded further using additional protein separation techniques.

The list will be 25 benchmarked to plasma protein spectral library published from human proteins.

WO 2019/113625 - 44- PCT I AU2018/000255 Table 12.

Potential Pain Biomarkers found in first few plasma sample analysis No Name of Protein Function of Protein 1 Alpha-1 acid glycoprotein APP; anti-inflammatory properties, immune system modulation 2 Alpha-2-macroglobulin 3 Alpha-2-macroglobulin variant APP; protease inhibition and clearance, inflammatory regulation 4 Alpha-2-macroglobulin variant 4 5 Alpha-2-macroglobulin variant 5 6 Apolipoprotein A-I APP; reverse cholesterol transport, anti- 7 Apolipoprotein A-II inflammatory and anti-coagulant activities 8 Apolipoprotein C-111 9 Ceruloplasmin (ferroxidase) APP; iron oxidation, free radical scavenging 10 Chain D, The Three-Dimensional Cytokine; Neutralizes the anticoagulant Structure Of Bovine Platelet effect of heparin, chemotactic for Factor 4 At 3.0 Angstroms neutrophils and monocytes.

Inhibits Resolution endothelial cell proliferation. 11 C-reactive protein precursor APP; It regulate the immune system during the early stage of an infection, plays a role in destroying infectious agents, minimizing tissue damage, and facilitating tissue repair and regeneration.

WO 2019/113625 - 45 - PCT I AU2018/000255 12 13 14 16 17 18 19 Fibrinogen beta chain APP; involved in blood coagulation, cellular Fibrinogen, alpha polypeptide and matrix interactions, endothelial cell precursor Haptoglobin Lactoferrin Lipopolysaccha ride protein Paraoxonase 1 Plasminogen Plasminogen precursor Regakine-1 precursor proliferation, inflammatory response, angiogenesis, neoplasia.

APP; haemoglobin binding protein, iron elimination control, anti-oxidant/ antiinflammatory role, immunomodulation.

APP; iron-binding glycoprotein, antimicrobial, anti-inflammatory, anti- cancer activities, immune system modulation. binding APP; innate immune response, Proinflammatory activity in high concentration and anti-inflammatory activity in low concentration.

Enzyme having antioxidant effect.

It has a protective effect against oxidation of lipoproteins.

APP; Anti-coagulant properties by fibrinolysis, cell migration enhancer, inflammatory response regulation.

Cytokine; Chemotactic activity for neutrophils and lymphocytes.

Binds to heparin.

WO 2019/113625 - 46- PCT I AU2018/000255 21 Serum amyloid A APP; lmmunomodulation, binding to cholesterol and opsonisation. 22 Transferrin APP; Iron binding blood plasma glycoprotein.

Cytokines and neuropeptides are very low abundance proteins and are not likely to be in concentrations detectable in plasma by SWATH-MS analysis.

However, multiple reaction monitoring (MRM) is the technique that a11ow to detect proteins with very low 5 concentration, such as cytokines.

With SWATH-MS, few highly abundant bovine cytokines like Regakine 1, Bovine platelet factor-4 (PF4/CXCL4) and Hemofiltrate CC Chemokine-1 (HCC-1/CCL14) can be detected and we have already detected Regakine 1 and platelet factor 4(PF4/CXCL4) in cattle sample analysis for the spectral library.

Regakine 1 is a naturally abundant cytokine in bovine serum (100 ng/mL).

A preliminary analysis of the proteins identified was undertaken usmg Principal Component Analysis (PCA) within the MarkerView software package (Figure 21).

This analysis looked at a comparison of groups for all time points (Figure 21 a), a comparison of dehorning vs. sham (Figure 21 b) and a comparison of treatment vs. placebo (Figure 21 15 c).

Although further analysis and validation is required, there appears to be clear effects of treatment and, possibly, a better outcome ( efficacy) with the transdermal formulation compared to IM.

Table 13 -NSAID and vehicle screening data Drug Sample Vehicle Alcohol solvent Terpene concentration Buffer/E sample time Replic analysis Concentration NSAID cone # ID Solvent Solvent cone Co-solvent Co-solvent cone Terpene (mg/ml) VAP (hrs) ate cone (μg/ml) Ketoprofen 50% KET451 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 0.5 0.01 0.03 Ketoprofen 50% KET452 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 2 0.005 0.Q15 Ketoprofen 50% KET453 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 4 0.01 0.03 Ketoprofen 50% KET454 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 6 0.005 0.Q15 Ketoprofen 50% KET455 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 8 0.005 0.015 Ketoprofen 50% KET456 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 0.5 0.006 0.Q18 Ketoprofen 50% KET457 KET31 Ethanol 70% EthOH None 0 Menthol so NA 2 en 0.006 0.018 C cr Ketoprofen 50% KET458 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 4 !!l. 0.004 0.012 e Ketoprofen 50% KET459 KET31 Ethanol 70% EthOH None 0 Menthol so NA 6 ro 0.005 0.015 :e:n:, Ketoprofen 50% KET460 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 8 0.003 0.009 (I) !2.

Ketoprofen 50% KET461 KET31 Ethanol 70% EthOH None 0 Menthol so NA 0.5 ;a 0.006 0.018~ C Ketoprofen 50% KET462 KET31 Ethanol 70% EthOH None 0 Menthol 50 NA 2 1D 0.006 0.Q18 N 0) Ketoprofen 50% KET463 KET31 Ethanol 70% EthOH None 0 Menthol so NA 4 0.003 0.009 ;o 0 Ketoprofen 50% KET464 KET31 Ethanol 70% EthOH None 0 Menthol so NA 6 ► 0.003 0.009 C Ketoprofen 50% KET465 KET31 Ethanol 70% EthOH None 0 Menthol so NA 8 0.004 0.012 Ketoprofen 50% KET466 KET32 lsopropanol 70% IPN None 0 Menthol so NA 0.5 0.004 0.012 Ketoprofen 50% KET467 KET32 lsopropano! 70% IPN None 0 Menthol so NA 2 0.252 0.756 Ketoprofen 50% KET468 KET32 lsopropanol 70% IPN None 0 Menthol so NA 4 0.005 0.015 Ketoprofen 50% KET469 KET32 lsopropano! 70% IPN None 0 Menthol so NA 6 0.006 0.018 Ketoprofen 50% KET470 KET32 lsopropanol 70% IPN None 0 Menthol 50 NA 8 0.008 0.024 Ketoprofen 50% KET471 KET32 lsopropanol 70% IPN None 0 Menthol so NA 0.5 0.004 0.012 Ketoprofen 50% KET472 KET32 lsopropanol 70% IPN None 0 Menthol so NA 2 0.017 0.051 Ketoprofen 50% KET473 KET32 lsopropanol 70% IPN None 0 Menthol so NA 4 0.004 0.012 Ketoprofen 50% KET474 KET32 lsopropanol 70% IPN None 0 Menthol so NA 6 0.004 0.012 Ketoprofen 50% KET475 KET32 lsopropanol 70% IPN None 0 Menthol so NA 8 0.004 0.012 Ketoprofen 50% KET476 KET32 lsopropanol 70% IPN None 0 Menthol 50 NA 0.5 0.025 0.075 ~ N 0 ""' ~ w""""'' 0'I N Ul ""d (") '"3 s;;: ~ N 0 ""' ~ 0 N Ul Ul ~ 0 "' 0 ."u.'., ""'' "' 0 "' 0 I 0 "' ,,..I.. ~ Ketoprofen 50% KET477 KET32 lsopropanol 70% IPN None 0 Menthol so NA 2 3 0.007 0.021 0 N Ketoprofen 50% KET478 KET32 lsopropanol 70% IPN None 0 Menthol 50 NA 4 3 0.005 O.Q15 0 ""' 1,0 Ketoprofen 50% KET479 KET32 lsopropanol 70% IPN None 0 Menthol so NA 6 3 0.003 0.009 -""""'' Ketoprofen 50% KET480 KET32 lsopropanol 70% IPN None 0 Menthol 50 NA 8 3 0.005 O.Q15 w 0'I N Flunixin 50% KET481 KET33 Ethanol 70% EthOH None 0 Menthol so NA 0.5 1 0 Ul Flunixin 50% KET482 KET33 Ethanol 70% EthOH None 0 Menthol 50 NA 2 1 ---- 0 Flunixin 50% KET483 KET33 Ethanol 70% EthOH None 0 Menthol so NA 4 1 0 Flunixin 50% KET484 KET33 Ethanol 70% EthOH None 0 Menthol so NA 6 1 0 Flunixin 50% KET485 KET33 Ethanol 70% EthOH None 0 Menthol so NA 8 1 0 en Flunixin 50% KET486 KET33 Ethanol 70% EthOH None 0 Menthol so NA 0.5 2 0 C cr Flunixin 50% KET487 KET33 Ethanol 70% EthOH None 0 Menthol so NA 2 2 0 !!l. e ~ ro Flunixin 50% KET488 KET33 Ethanol 70% EthOH None 0 Menthol so NA 4 2 0 0 en "0 ' :::, Flunixin 50% KET489 KET33 Ethanol 70% EthOH None 0 Menthol so NA 6 2 0 "' (I) .u.., !2.

Flunixin Ethanol 70% EthOH Menthol .. ;a 50% KET490 KET33 None 0 so NA 8 2 ---- ooe ""'' "' C Flunixin Ethanol 70% EthOH Menthol 1D 50% KET491 KET33 None 0 so NA 0.5 3 0 "' 0 N I ;0o) Flunixin 50% KET492 KET33 Ethanol 70% EthOH None 0 Menthol so NA 2 3 ---- 0 "' ,.I. 0 Flunixin 50% KET493 KET33 Ethanol 70% EthOH None 0 Menthol so NA 4 3 0 ,.. ► C Flunixin 50% KET494 KET33 Ethanol 70% EthOH None 0 Menthol so NA 6 3 ---- 0 Flunixin 50% KET495 KET33 Ethanol 70% EthOH None 0 Menthol so NA 8 3 0 Tolfenamic acid 50% KET496 KET34 Ethanol 70% EthOH None 0 Menthol so NA 0.5 1 0 Tolfenamic acid 50% KET497 KET34 Ethanol 70% EthOH None 0 Menthol so NA 2 1 0 Tolfenamic acid 50% KET498 KET34 Ethanol 70% EthOH None 0 Menthol so NA 4 1 0 Tolfenamic ""d acid 50% KET499 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 6 1 ---- 0 (") Tolfenamic '"3 acid 50% KETSOO KET34 Ethanol 70% EthOH None 0 Menthol so NA 8 1 0 s;;: Tolfenamic ~ acid 50% KETSOl KET34 Ethanol 70% EthOH None 0 Menthol so NA 0.5 2 0 N ---- 0 Tolfenamic "Q"C' acid 50% KET502 KET34 Ethanol 70% EthOH None 0 Menthol so NA 2 2 0 -0 Tolfenamic 0 acid 50% KET503 KET34 Ethanol 70% EthOH None 0 Menthol so NA 4 2 ---- 0 0 N Tolfenamic Ul acid 50% KET504 KET34 Ethanol 70% EthOH None 0 Menthol so NA 6 2 0 Ul Tolfenamic ~ acid 50% KET505 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 8 2 0 0 Tolfenamic N acid Tolfenamic 50% KET506 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 0.5 3 ---- 0 -1"0", 0' acid 50% KET507 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 2 3 0 ""' Tolfenamic w""' acid 50% KET508 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 4 3 0 0'I N Tolfenamic Ul acid 50% KET509 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 6 3 0.004 0.012 Tolfenamic acid 50% KET510 KET34 Ethanol 70% EthOH None 0 Menthol 50 NA 8 3 0 Ketoprofen 10% KET5ll KET35 lsopropanol 70% IPN None 0 None 0 NA 0.5 1 0.011 0.033 Ketoprofen 10% KET512 KET35 lsopropanol 70% IPN None 0 None 0 NA 2 1 0.005 O.Dl5 Ketoprofen 10% KET513 KET35 lsopropanol 70% IPN None 0 None 0 NA 4 1 0.008 0.024 en Ketoprofen 10% KET514 KET35 lsopropanol 70% IPN None 0 None 0 NA 6 1 0.022 0.066 C cr !!l.

Ketoprofen 10% KET515 KET35 lsopropanol 70% IPN None 0 None 0 NA 8 1 0.066 0.198 e ~ ro Ketoprofen 10% KET516 KET35 lsopropanol 70% IPN None 0 None 0 NA 0.5 2 0.005 0.015 0 en "0 ' :::, "' (I) Ketoprofen 10% KET517 KET35 lsopropanol 70% IPN None 0 None 0 NA 2 2 0.016 0.048 .u.., !2. .. 1,0 ""'' ;a Ketoprofen 10% KET518 KET35 lsopropanol 70% IPN None 0 None 0 NA 4 2 0.005 0.015 "' C 0 1D "' Ketoprofen 10% KET519 KET35 lsopropanol 70% IPN None 0 None 0 NA 6 2 0.04 0.12 0 N I 0 ;0o) "' Ketoprofen 10% KET520 KET35 lsopropanol 70% IPN None 0 None 0 NA 8 2 0.125 0.375 ,.I . 0 ,.. ► Ketoprofen 10% KET521 KET35 lsopropanol 70% IPN None 0 None 0 NA 0.5 3 0.006 O.Dl8 C Ketoprofen 10% KET522 KET35 lsopropanol 70% IPN None 0 None 0 NA 2 3 0.008 0.024 Ketoprofen 10% KET523 KET35 lsopropanol 70% IPN None 0 None 0 NA 4 3 0.035 0.105 Ketoprofen 10% KET524 KET35 lsopropanol 70% IPN None 0 None 0 NA 6 3 0.141 0.423 Ketoprofen 10% KET525 KET35 lsopropanol 70% IPN None 0 None 0 NA 8 3 0.415 1.245 Ketoprofen 50% KET526 KET36 Ethanol 50"/4 EthOH None 0 Menthol 50 NA 0.5 1 0.01 0.03 ""d Ketoprofen 50% KET527 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 2 1 0.008 0.024 (") '"3 Ketoprofen 50% KET528 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 4 1 0.01 0.03 s;;: ~ Ketoprofen 50% KET529 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 6 1 0.009 0.027 N 0 ""' Ketoprofen 50% KET530 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 8 1 0.007 0.021 -QC) 0 Ketoprofen 50% KET531 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 0.5 2 0.011 0.033 0 N Ul Ketoprofen 50% KET532 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 2 2 0.006 0.018 Ul ~ Ketoprofen 50% KET533 KET36 Ethanol 50% EthOH None 0 Menthol so NA 4 2 0.006 0.018 0 N Ketoprofen 50% KET534 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 6 2 0.008 0.024 0 ""' 1,0 Ketoprofen 50% KET535 KET36 Ethanol 50% EthOH None 0 Menthol so NA 8 2 0.006 0.018 -""""'' Ketoprofen 50% KET536 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 0.5 3 0.007 0.021 w 0'I N Ketoprofen 50% KET537 KET36 Ethanol SO% EthOH None 0 Menthol so NA 2 3 0.007 0.021 Ul Ketoprofen 50% KET538 KET36 Ethanol 50% EthOH None 0 Menthol 50 NA 4 3 0.011 0.033 Ketoprofen 50% KET539 KET36 Ethanol 50% EthOH None 0 Menthol so NA 6 3 0.023 0.069 Ketoprofen 50% KET540 KET36 Ethanol 50% EthOH None 0 Menthol so NA 8 3 0.128 0.384 Ketoprofen 50% KET541 KET37 Ethanol 50% IPN None 0 Menthol so NA 0.5 1 0.112 0.336 en Ketoprofen 50% KET542 KET37 Ethanol 50% IPN None 0 Menthol so NA 2 1 0.029 0.087 C cr Ketoprofen 50% KET543 KET37 Ethanol 50% IPN None 0 Menthol so NA 4 1 0.009 0.027 !!l. e ~ ro Ketoprofen 50% KET544 KET37 Ethanol 50% IPN None 0 Menthol so NA 6 1 0.01 0.03 0 en "0 ' :::, Ketoprofen 50% KET545 KET37 Ethanol 50% IPN None 0 Menthol so NA 8 1 0.021 0.063 "u', (I) ... !2.

Ketoprofen Ethanol Menthol Ul "' ;a 50% KET546 KET37 50% IPN None 0 so NA 0.5 2 0.009 0.0270 "' "' C Ketoprofen Ethanol Menthol 1D 50% KET547 KET37 50% IPN None 0 so NA 2 2 0.013 0.039 "' 0 N I ;0o) Ketoprofen 50% KET548 KET37 Ethanol 50% IPN None 0 Menthol so NA 4 2 0.061 0.183 "' ,.I. 0 Ketoprofen 50% KET549 KET37 Ethanol 50% IPN None 0 Menthol so NA 6 2 0.143 0.429 ,.. ► C Ketoprofen 50% KET550 KET37 Ethanol 50% IPN None 0 Menthol so NA 8 2 0.236 0.708 Ketoprofen 50% KET551 KET37 Ethanol 50% IPN None 0 Menthol so NA 0.5 3 0.013 0.039 Ketoprofen 50% KET552 KET37 Ethanol 50% IPN None 0 Menthol so NA 2 3 0.005 0.015 Ketoprofen 50% KET553 KET37 Ethanol SO% IPN None 0 Menthol so NA 4 3 0.005 0.015 Ketoprofen 50% KET554 KET37 Ethanol 50% IPN None 0 Menthol 50 NA 6 3 0.007 0.021 ""d Ketoprofen 50% KET555 KET37 Ethanol 50% IPN None 0 Menthol so NA 8 3 0.005 0.015 (") '"3 Flunixin 50% KET556 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 0.5 1 ---- 0 s;;: Flunixin 50% KET557 KET38 Ethanol 50% EthOH None 0 Menthol so NA 2 1 0 ~ N Flunixin 50% KET558 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 4 1 ---- 0 ""' -QC) 0 Flunixin 50% KET559 KET38 Ethanol 50% EthOH None 0 Menthol so NA 6 1 ---- 0 0 N Flunixin 50% KET560 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 8 1 ----- 0 Ul Ul ~ Flunixin 50% KET561 KET38 Ethanol 50% EthOH None 0 Menthol so NA 0.5 2 0 0 N Flunixin 50% KET562 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 2 2 ---- 0 0 ""' 1,0 Flunixin 50% KET563 KET38 Ethanol 50% EthOH None 0 Menthol so NA 4 2 0 -""""'' Flunixin 50% KET564 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 6 2 ---- 0 w 0'I N Flunixin 50% KETS65 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 8 2 0 Ul Flunixin 50% KET566 KET38 Ethanol 50% EthOH None 0 Menthol 50 NA 0.5 3 ---- 0 Flunixin 50% KET567 KET38 Ethanol 50% EthOH None 0 Menthol so NA 2 3 0 Flunixin 50% KET568 KET38 Ethanol 50% EthOH None 0 Menthol so NA 4 3 0 Flunixin 50% KET569 KET38 Ethanol 50% EthOH None 0 Menthol so NA 6 3 0 en Flunixin 50% KET570 KET38 Ethanol 50% EthOH None 0 Menthol so NA 8 3 0 C Tolfenamic cr !!l. acid 50% KET571 KET39 Ethanol 50% EthOH None 0 Menthol 50 NA 0.5 1 ---- 0 e Tolfenamic ~ ro acid 50% KET572 KET39 Ethanol 50% EthOH None 0 Menthol 50 NA 2 1 0 0 en Tolfenamic "0 ' :::, acid 50% KET573 KET39 Ethanol 50% EthOH None 0 Menthol 50 NA 4 1 0.004 0.012 "' (I) .u.., !2.

Tolfenamic Ul "' ;a acid 50% KET574 KET39 Ethanol 50% EthOH None 0 Menthol so NA 6 1 o""' "' "' C Tolfenamic 0 1D acid 50% KET575 KET39 Ethanol 50% EthOH None 0 Menthol so NA 8 1 0 "0 ' N I Tolfenamic 0 ;0o) "' acid 50% KET576 KET39 Ethanol 50% EthOH None 0 Menthol so NA 0.5 2 0.006 0.018 ,.I . 0 Tolfenamic ,.. ► acid 50% KET577 KET39 Ethanol 50% EthOH None 0 Menthol so NA 2 2 0 C Tolfenamic acid 50% KET578 KET39 Ethanol 50% EthOH None 0 Menthol 50 NA 4 2 ---- 0 Tolfenamic acid 50% KET579 KET39 Ethanol 50% EthOH None 0 Menthol so NA 6 2 0 Tolfenamic acid 50% KET580 KET39 Ethanol 50% EthOH None 0 Menthol 50 NA 8 2 ---- 0 Tolfenamic acid 50% KET581 KET39 Ethanol 50% EthOH None 0 Menthol so NA 0.5 3 0 Tolfenamic acid 50% KET582 KET39 Ethanol 50% EthOH None 0 Menthol so NA 2 3 0.009 0.027 ""d Tolfenamic (") acid 50% KET583 KET39 Ethanol 50% EthOH None 0 Menthol so NA 4 3 0 '"3 Tolfenamic s;;: acid 50% KET584 KET39 Ethanol 50% EthOH None 0 Menthol so NA 6 3 ---- 0 ~ Tolfenamic N acid 50% KET585 KET39 Ethanol 50% EthOH None 0 Menthol so NA 8 3 ---- 0 ""' -QC) Ketoprofen 10% KET586 KET40 lsopropanol 50% IPN None 0 None 0 NA 0.5 1 0.014 0.042 Ketoprofen 10% KET587 KET40 lsopropanol 50"/4 IPN None 0 None 0 NA 2 1 0.011 0.033 N Ul Ul Ketoprofen 10% KET588 KET40 lsopropanol 50% IPN None 0 None 0 NA 4 1 0.009 0.027 ~ Ketoprofen 10% KET589 KET40 lsopropanol 50% IPN None 0 None 0 NA 6 1 0.007 0.021 0 N Ketoprofen 10% KET590 KET40 lsopropanol 50% IPN None 0 None 0 NA 8 1 0.008 0.024 0 ""' 1,0 Ketoprofen 10% KET591 KET40 lsopropanol 50% IPN None 0 None 0 NA 0.5 2 0.012 0.036 -""""'' Ketoprofen 10% KET592 KET40 lsopropanol 50% IPN None 0 None 0 NA 2 2 0.005 O.D15 w 0'I N Ketoprofen 10% KET593 KET40 lsopropano! 50% IPN None 0 None 0 NA 4 2 0.009 0.027 Ul Ketoprofen 10% KET594 KET40 lsopropanol 50% IPN None 0 None 0 NA 6 2 0.007 0.021 Ketoprofen 10% KET595 KET40 lsopropanol 50% IPN None 0 None 0 NA 8 2 0.007 0.021 Ketoprofen 10% KET596 KET40 lsopropanol 50% IPN None 0 None 0 NA 0.5 3 0.02 0.06 Ketoprofen 10% KET597 KET40 lsopropanol 50% IPN None 0 None 0 NA 2 3 0.011 0.033 en Ketoprofen 10% KET598 KET40 lsopropanol 50% IPN None 0 None 0 NA 4 3 0.021 0.063 C cr Ketoprofen 10% KET599 KET40 lsopropanol 50% IPN None 0 None 0 NA 6 3 0.013 0.039 !!l. e ~ ro Ketoprofen 10% KET600 KET40 lsopropanol 50% IPN None 0 None 0 NA 8 3 0.013 0.039 0 en O.lM "0 ' :::, Ketoprofen 10% KET601 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 1 0.007 0.021 "' (I) u, O.lM ... !2.

Ul "' ;a Ketoprofen 10% KET602 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 1 0.007 0.021N "' O.lM "' C 0 1D Ketoprofen 10% KET603 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 1 0.083 0.249 "' 0 N O.lM I 0) ;o Ketoprofen 10% KET604 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 1 0.161 0.483 "I ' O.lM ,.. 0 ,.. ► Ketoprofen 10% KET605 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 1 1.396 4.188 C O.lM Ketoprofen 10% KET606 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 2 0.002 0.006 O.lM Ketoprofen 10% KET607 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 2 0.009 0.027 O.lM Ketoprofen 10% KET608 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 2 0.01 0.03 O.lM Ketoprofen 10% KET609 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 2 0.062 0.186 O.lM Ketoprofen 10% KET610 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 2 0.693 2.079 ""d O.lM (") Ketoprofen 10% KET611 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 3 0.001 0.003 '"3 O.lM s;;: Ketoprofen 10% KET612 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 3 0.002 0.006 ~ O.lM N Ketoprofen 10% KET613 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 3 0.019 0.057 ""' 0.lM -QC) Ketoprofen 10% KET614 KET41 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 3 0.245 0.735 0 O.lM 0 Ketoprofen 10% KET615 KET41 Ethanol 70"/4 EthOH Propylene glycol 30% PPG None 0 citrate 8 3 0.687 2.061 N Ul 0.lM Ul Ketoprofen 10% KET616 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 1 0.001 0.003 O.lM ~ Ketoprofen 10% KET617 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 1 0.002 0.006 0 O.lM N Ketoprofen 10% KET618 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 Ocit.rlMat e 6 1 0.324 0.972 -"10", 0' Ketoprofen 10% KET619 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 1 0.474 1.422 """"'' O.lM w Ketoprofen 10% KET620 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 1 0.816 2.448 0'I N O.lM Ul Ketoprofen 10% KET621 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 2 0.007 0.021 O.lM Ketoprofen 10% KET622 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 2 0.016 0.048 O.lM Ketoprofen 10% KET623 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 2 0.017 0.051 O.lM Ketoprofen 10% KET624 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 2 0.365 1.095 O.lM Ketoprofen 10% KET625 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 2 1.459 4.377 en 0.lM C Ketoprofen 10% KET626 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 3 0.003 0.009 cr !!l. O.lM e Ketoprofen 10% KET627 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 3 0.009 0.027 ~ ro O.lM 0 en Ketoprofen 10% KET628 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 3 0.007 0.021 "0 ' :::, "' (I) O.lM .u.., !2.

Ketoprofen 10% KET629 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 3 0.378 l.134~ ""'' ;a O.lM "' C Ketoprofen 10% KET630 KET42 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 3 0.513 1.539 0 1D "' O.lM 0 N I Ketoprofen 10% KET631 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 1 0.002 0.006 0 ;0o) "' O.lM ,.I . 0 Ketoprofen 10% KET632 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 2 1 0.003 0.009 ,.. ► O.lM C Ketoprofen 10% KET633 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 1 0.027 0.081 O.lM Ketoprofen 10% KET634 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 6 1 0.095 0.285 O.lM Ketoprofen 10% KET635 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 1 1.075 3.225 O.lM Ketoprofen 10% KET636 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 2 0.013 0.039 O.lM Ketoprofen 10% KET637 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 2 2 0.013 0.039 O.lM ""d Ketoprofen 10% KET638 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 2 0.142 0.426 (") '"3 O.lM s;;: Ketoprofen 10% KET639 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 6 2 0.411 1.233 O.lM ~ N Ketoprofen 10% KET640 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 2 0.826 2.478 0 O.lM ""' QC) Ketoprofen 10% KET641 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 3 0.003 0.009 -0 O.lM 0 Ketoprofen 10% KET642 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 3 0.002 0.006 0 N 0.1M Ul Ketoprofen 10% KET643 KET43 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 2 3 0.379 1.137 Ul O.lM ~ Ketoprofen 10% KET644 KET43 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 4 3 1.119 3.357 0 O.lM N Ketoprofen 10% KET645 KET43 Ethanol 70% EthOH SOulepye! rafilnceo hol 30%0A None 0 Ocit.rlMat e 6 3 1.132 3.396 -"10", 0' Ketoprofen 10% KET646 KET44 None None Arlasolve 100%SRArl 0 citrate 0.5 1 0.008 0.024 ""' Superfine O.lM w""' Ketoprofen 10% KET647 KET44 None None Arla solve 100%SRArl 0 citrate 2 1 0.003 0.009 0'I N Superfine O.lM Ul Ketoprofen 10% KET648 KET44 None None Arlasolve 100%SRArl 0 citrate 4 1 0.012 0.036 Superfine O.lM Ketoprofen 10% KET649 KET44 None None Arla solve 100%SRArl 0 citrate 6 1 0.015 0.045 Superfine O.lM Ketoprofen 10% KET650 KET44 None None Arla solve 100%SRArl 0 citrate 8 1 0.015 0.045 Superfine O.lM Ketoprofen 10% KET651 KET44 None None Arla solve 100%SRArl 0 citrate 0.5 2 0.006 0,018 Superfine O.lM Ketoprofen 10% KET652 KET44 None None Arla solve 100%SRArl 0 citrate 2 2 0.019 0.057 en Superfine 0.lM C Ketoprofen 10% KET653 KET44 None None Arla solve 100%SRArl 0 citrate 4 2 0.009 0.027 cr !!l.

Superfine O.lM e Ketoprofen 10% KET654 KET44 None None Arla solve 100%SRArl 0 citrate 6 2 0.02 0.06 ~ ro Superfine O.lM 0 en Ketoprofen 10% KET655 KET44 None None Arla solve 100%SRArl 0 citrate 8 2 0.028 0.084 "0 ' :::, Superfine "' (I) O.lM .u.., !2.

Ketoprofen 10% KET656 KET44 None None Arla solve 100%SRArl 0 citrate 8 3 0.005 0.Q15'-t. ""'' ;a Superfine O.lM "' C Ketoprofen 10% KET657 KET44 None None Arlasolve 100%SRArl 0 citrate 6 3 0.01 0.03 0 1D "' Superfine 0.1M 0 N I Ketoprofen 10% KET658 KET44 None None Arla solve 100%SRArl 0 citrate 4 3 0.005 O.D15 0 ;0o) "' Superfine 0.1M ,.I . 0 Ketoprofen 10% KET659 KET44 None None Arla solve 100%SRArl 0 citrate 2 3 0.011 0.033 ,.. ► Superfine 0.1M C Ketoprofen 10% KET660 KET44 None None Arla solve 100%SRArl 0 citrate 0.5 3 0.002 0.006 Crodamol STS- O.lM Ketoprofen 10% KET661 KET45 None None LQ(MH) 100% Crodamol 0 citrate 8 1 0.009 0.027 Crodamol STS- O.lM Ketoprofen 10% KET662 KET45 None None LQ(MH) 100% Crodamol 0 citrate 6 1 0.006 0.018 Crodamol STS- 0.1M Ketoprofen 10% KET663 KET45 None None LQ(MH) 100% Crodamol 0 citrate 0.5 1 0.025 0.075 Crodamol STS- 0.1M Ketoprofen 10% KET664 KET45 None None LQ(MH) 100% Crodamol 0 citrate 4 1 0.052 0.156 Crodamol STS- O.lM ""d Ketoprofen 10% KET665 KET45 None None LQ(MH) 100% Crodamol 0 citrate 2 1 1.017 3.051 (") '"3 Crodamol ST5- 0.1M s;;: Ketoprofen 10% KET666 KET45 None None LQ(MH) 100% Crodamol 0 citrate 4 2 0.024 0.072 Crodamol STS- O.lM ~ N Ketoprofen 10% KET667 KET45 None None LQ(MH) 100% Crodamol 0 citrate 6 2 0.026 O.Q78 0 Crodamol ST5- 0.1M ""' QC) Ketoprofen 10% KET668 KET45 None None LQ(MH) 100% Crodamol 0 citrate 0.5 2 0.645 1.935 -0 Crodamol STS- O.lM 0 Ketoprofen 10% KET669 KET45 None None LQ(MH) 100% Crodamol 0 citrate 2 2 0.54 1.62 0 N Crodamol STS- O.lM Ul Ketoprofen 10% KET670 KET45 None None LQ(MH) 100% Crodamol 0 citrate 8 2 0.645 1.935 Ul Crodamol STS· O.lM ~ Ketoprofen 10% KET671 KET45 None None LQ(MH) 100% Crodamol 0 citrate 2 3 0.012 0.036 0 Crodamol STS· O.lM N Ketoprofen 10% KET672 KET45 None None CLQro(dMaHm) ol STS· 100% Crodamol 0 Ocit.rlMat e 4 3 0.01 0.03 -"10", 0' Ketoprofen 10% KET673 KET45 None None LQ(MH) 100% Crodamol 0 citrate 6 3 0.053 0.159 ""' Crodamol STS· O.lM w""' Ketoprofen 10% KET674 KET45 None None LQ(MH) 100% Crodamol 0 citrate 8 3 0.179 0.537 0'I N Crodamol STS- O.lM Ul Ketoprofen 10% KET675 KET45 None None LQ(MH) 100% Crodamol 0 citrate 0.5 3 0.213 0.639 O.lM Flunixin 10% KET676 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 1 0.014 0.042 O.lM Flunixin 10% KET677 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 1 0 O.lM Flunixin 10% KET678 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 1 ---- 0 O.lM Flunixin 10% KET679 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 1 0.048 0.144 en 0.lM C Flunixin 10% KET680 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 1 ---- 0 cr !!l. O.lM e Flunixin 10% KET681 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 2 ---- 0 ~ ro O.lM 0 en Flunixin 10% KET682 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 2 0.008 0.024 "0 ' :::, "' (I) O.lM .u.., !2.

Flunixin 10% KET683 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 2 0.12 0.368: ""'' ;a O.lM "' C Flunixin 10% KET684 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 2 0.241 0.723 0 1D "' O.lM 0 N I Flunixin 10% KET685 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 2 0.106 0.318 0 ;0o) "' O.lM ,.I . 0 Flunixin 10% KET686 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 3 ---- 0 ,.. ► O.lM C Flunixin 10% KET687 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 3 ---- 0 O.lM Flunixin 10% KET688 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 3 ---- 0 O.lM Flunixin 10% KET689 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 3 0.012 0.036 O.lM Flunixin 10% KET690 KET46 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 3 0.012 0.036 O.lM Flunixin 10% KET691 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol so citrate 0.5 1 0.009 0.027 O.lM ""d Flunixin 10% KET692 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol so citrate 2 1 0.02 0.06 (") '"3 O.lM s;;: Flunixin 10% KET693 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol so citrate 4 1 0.013 0.039 O.lM ~ N Flunixin 10% KET694 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 1 0.008 0.024 0 O.lM ""' QC) Flunixin 10% KET695 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 1 O.QlS 0.045 -0 O.lM 0 Flunixin 10% KET696 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 2 ---- 0 0 N O.lM Ul Flunixin 10% KET697 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 2 0.039 0.117 Ul O.lM ~ Flunixin 10% KET698 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 2 0 0 O.lM N Flunixin 10% KET699 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 Ocit.rlMat e 6 2 ---- 0 -"10", 0' Flunixin 10% KET700 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 2 0.005 0.015 """"'' O.lM w Flunixin 10% KET701 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 3 0 0'I N O.lM Ul Flunixin 10% KET702 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 3 0.007 0.021 O.lM Flunixin 10% KET703 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 3 0.005 0.015 O.lM Flunixin 10% KET704 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 3 0 O.lM Flunixin 10% KET705 KET47 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 3 ---- 0 O.lM Flunixin 10% KET706 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 1 0.01 0.03 en 0.lM C Flunixin 10% KET707 KET48 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 2 1 0.007 0.021 cr !!l. O.lM e Flunixin 10% KET708 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 1 0.007 0.021 ~ ro O.lM 0 en Flunixin 10% KET709 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 6 1 0.005 0.015 "0 ' :::, "' (I) O.lM .u.., !2.

Flunixin 10% KET710 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 1 0.01 o.o3g: ""'' ;a O.lM "' C Flunixin 10% KET711 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 2 0.008 0.024 0 1D "' O.lM 0 N I Flunixin 10% KET712 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 2 2 0.006 0.018 0 ;0o) "' O.lM ,.I . 0 Flunixin 10% KET713 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 2 0.007 0.021 ,.. ► O.lM C Flunixin 10% KET714 KET48 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 6 2 0.007 0.021 O.lM Flunixin 10% KET715 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 2 0.007 0.021 O.lM Flunixin 10% KET716 KET48 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 0.5 3 ---- 0 O.lM Flunixin 10% KET717 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 2 3 0.222 0.666 O.lM Flunixin 10% KET718 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 3 0 O.lM ""d Flunixin 10% KET719 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 6 3 0 (") '"3 O.lM s;;: Flunixin 10% KET720 KET48 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 3 0.008 0.024 Superfine O.lM ~ N Flunixin 10% KET721 KET49 None None Arla solve 100%SRArl 0 citrate 0.5 1 ---- 0 0 Superfine O.lM ""' QC) Flunixin 10% KET722 KET49 None None Arla solve 100%SRArl 0 citrate 2 1 0.005 O.DlS -0 Superfine O.lM 0 Flunixin 10% KET723 KET49 None None Arla solve 100%5RArl 0 citrate 4 1 0.005 0.015 0 N Superfine O.lM Ul Flunixin 10% KET724 KET49 None None Arla solve 100%SRArl 0 citrate 6 1 0.007 0.021 Ul Superfine O.lM ~ Flunixin 10% KET725 KET49 None None Arla solve 100%SRArl 0 citrate 8 1 0.026 0.078 0 Superfine O.lM N Flunixin 10% KET726 KET49 None None SArulap esorflivnee 100%SRArl 0 Ocit.rlMat e 0.5 2 ---- 0 -"10", 0' Flunixin 10% KET727 KET49 None None Arla solve 100%SRArl 0 citrate 2 2 0 ""' Superfine O.lM w""' Flunixin 10% KET728 KET49 None None Arla solve 100%SRArl 0 citrate 4 2 0 0'I N Superfine O.lM Ul Flunixin 10% KET729 KET49 None None Arlasolve 100%SRArl 0 citrate 6 2 0.006 0.018 Superfine O.lM Flunixin 10% KET730 KET49 None None Arla solve 100%SRArl 0 citrate 8 2 0 Superfine O.lM Flunixin 10% KET731 KET49 None None Arla solve 100%SRArl 0 citrate 0.5 3 0.007 0.021 Superfine O.lM Flunixin 10% KET732 KET49 None None Arla solve 100%SRArl 0 citrate 2 3 ---- 0 Superfine 0.1M Flunixin 10% KET733 KET49 None None Arla solve 100%SRArl 0 citrate 4 3 ---- 0 en Superfine 0.1M C Flunixin 10% KET734 KET49 None None Arla solve 100%SRArl 0 citrate 6 3 ---- 0 cr !!l.

Superfine 0.1M e Flunixin 10% KET735 KET49 None None Arla solve 100%SRArl 0 citrate 8 3 ---- 0 ~ ro Crodamol STS- O.lM 0 en Flunixin 10% KET736 KETSO None None LQ(MH) 100% Crodamol 0 citrate 0.5 1 0.012 0.036 "0 ' :::, Crodamol STS- "' (I) O.lM .u.., !2.

Flunixin 10% KET737 KETSO None None LQ(MH) 100% Crodamol 0 citrate 2 1 0.011 0.033~ ""'' ;a Crodamol STS- O.lM "' C Flunixin 10% KET738 KETSO None None LQ(MH) 100% Crodamol 0 citrate 4 1 0.006 0.018 0 1D "' Crodamol STS- 0.1M 0 N I Flunixin 10% KET739 KETSO None None LQ(MH) 100% Crodamol 0 citrate 6 1 0.009 0.027 0 ;0o) "' Crodamol STS- 0.1M ,.I . 0 Flunixin 10% KET740 KETSO None None LQ(MH) 100% Crodamol 0 citrate 8 1 0.007 0.021 ,.. ► Crodamol STS- O.lM C Flunixin 10% KET741 KETSO None None LQ(MH) 100% Crodamol 0 citrate 0.5 2 0.007 0.021 Crodamol STS- O.lM Flunixin 10% KET742 KETSO None None LQ(MH) 100% Crodamol 0 citrate 2 2 0.013 0.039 Crodamol STS- O.lM Flunixin 10% KET743 KETSO None None LQ(MH) 100% Crodamol 0 citrate 4 2 0.006 0.018 Crodamol STS- O.lM Flunixin 10% KET744 KETSO None None LQ(MH) 100% Crodamol 0 citrate 6 2 0.006 0,018 Crodamol STS- O.lM Flunixin 10% KET745 KETSO None None LQ(MH) 100% Crodamol 0 citrate 8 2 0.014 0.042 Crodamol STS- 0.1M ""d Flunixin 10% KET746 KETSO None None LQ(MH) 100% Crodamol 0 citrate 0.5 3 0 (") '"3 Crodamol STS- O.lM s;;: Flunixin 10% KET747 KETSO None None LQ(MH) 100% Crodamol 0 citrate 2 3 0.008 0.024 Crodamol STS- O.lM ~ N Flunixin 10% KET748 KETSO None None LQ(MH) 100% Crodamol 0 citrate 4 3 0.012 0.036 0 Crodamol STS- O.lM ""' QC) Flunixin 10% KET749 KETSO None None LQ(MH) 100% Crodamol 0 citrate 6 3 0.019 0.057 -0 Crodamol STS- O.lM 0 Flunixin 10% KET750 KETSO None None LQ(MH) 100% Crodamol 0 citrate 8 3 ---- 0 0 N Tolfenamic O.lM Ul acid 10% KET751 KETSl Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 1 0.004 0.012 Ul Tolfenamic O.lM ~ acid 10% KET752 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 1 0.011 0.033 0 Tolfenamic O.lM N acid 10% KET753 KET51 Tolfenamic Ethanol 70% EthOH Propylene glycol 30% PPG None 0 Ocit.rlMat e 4 1 ---- 0 -"10", 0' acid 10% KET754 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 1 0.004 0.012 ""' Tolfenamic O.lM w""' acid 10% KET755 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 1 0.006 0.018 0'I N Tolfenamic O.lM Ul acid 10% KET756 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 2 0.015 0.045 Tolfenamic O.lM acid 10% KET757 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 2 0.01 0.03 Tolfenamic O.lM acid 10% KET758 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 2 0.004 0.012 Tolfenamic O.lM acid 10% KET759 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 2 0.005 0.015 Tolfenamic O.lM acid 10% KET760 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 2 0.005 0.015 en Tolfenamic 0.lM C acid 10% KET761 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 0.5 3 ---- 0 cr !!l.

Tolfenamic O.lM e acid 10% KET762 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 2 3 ---- 0 ~ ro Tolfenamic 0.1M 0 en acid 10% KET763 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 4 3 0.003 0.009 "0 ' :::, Tolfenamic "' (I) O.lM .u.., !2. acid 10% KET764 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 6 3 0.004 0.012~ ""'' ;a Tolfenamic 0.1M "' C acid 10% KET765 KET51 Ethanol 70% EthOH Propylene glycol 30% PPG None 0 citrate 8 3 0.004 0.012 0 1D "' Tolfenamic O.lM 0 N I acid 10% KET766 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 1 0.003 0.009 0 ;0o) "' Tolfenamic 0.1M ,.I . 0 acid 10% KET767 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 1 0.004 0.012 ,.. ► Tolfenamic O.lM C acid 10% KET768 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 1 0.003 0.009 Tolfenamic O.lM acid 10% KET769 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 1 0.002 0.006 Tolfenamic O.lM acid 10% KET770 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 1 0.004 0.012 Tolfenamic O.lM acid 10% KET771 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 2 0.003 0.009 Tolfenamic O.lM acid 10% KET772 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 2 0.002 0.006 Tolfenamic O.lM ""d acid 10% KET773 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 2 0.004 0.012 (") '"3 Tolfenamic O.lM s;;: acid 10% KET774 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 2 0.003 0.009 Tolfenamic O.lM ~ N acid 10% KET775 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 8 2 0.007 0.021 0 Tolfenamic O.lM ""' QC) acid 10% KET776 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 0.5 3 0.002 0.006 -0 Tolfenamic O.lM 0 acid 10% KET777 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 2 3 ---- 0 0 N Tolfenamic O.lM Ul acid 10% KET778 KETSZ Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 4 3 0 Ul Tolfenamic O.lM ~ acid 10% KET779 KET52 Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 citrate 6 3 0 0 Tolfenamic O.lM N acid 10% KET780 KET52 Tolfenamic Ethanol 70% EthOH Propylene glycol 30% PPG Menthol 50 Ocit.rlMat e 8 3 0.004 0.012 -"10", 0' acid 10% KET781 KET53 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 1 0.002 0.006 ""' Tolfenamic O.lM w""' acid 10% KET782 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 2 1 0 0'I N Tolfenamic O.lM Ul acid 10% KET783 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 4 1 0.007 0.021 Tolfenamic O.lM acid 10% KET784 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 6 1 0.013 0.039 Tolfenamic O.lM acid 10% KET785 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 8 1 0.047 0.141 Tolfenamic O.lM acid 10% KET786 KET53 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 0.5 2 0.002 0.006 Tolfenamic O.lM acid 10% KET787 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 2 2 ---- 0 en Tolfenamic 0.lM C acid 10% KET788 KET53 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 4 2 0.003 0.009 cr !!l.

Tolfenamic O.lM e acid 10% KET789 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 6 2 0.009 0.027 ~ ro Tolfenamic O.lM 0 en acid 10% KET790 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 8 2 0.08 0.24 "0 ' :::, Tolfenamic "' (I) O.lM .u.., !2. acid 10% KET791 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 0.5 3 0.002 0.006~ ""'' ;a Tolfenamic O.lM "' C acid 10% KET792 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 2 3 0.005 0.015 0 1D "' Tolfenamic O.lM 0 N I acid 10% KET793 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 4 3 0.007 0.021 0 ;0o) "' Tolfenamic O.lM ,.I . 0 acid 10% KET794 KET53 Ethanol 70% EthOH Oley! alcohol 30%0A None 0 citrate 6 3 0.034 0.102 ,.. ► Tolfenamic O.lM C acid 10% KET795 KET53 Ethanol 70% EthOH Oleyl alcohol 30%0A None 0 citrate 8 3 0.04 0.12 Tolfenamic Superfine O.lM acid 10% KET796 KET54 None None Arla solve 100%SRArl 0 citrate 0.5 1 0.002 0.006 Tolfenamic Superfine O.lM acid 10% KET797 KET54 None None Arla solve 100%SRArl 0 citrate 2 1 ---- 0 Tolfenamic Superfine O.lM acid 10% KET798 KET54 None None Arla solve 100%SRArl 0 citrate 4 1 ----- 0 Tolfenamic Superfine O.lM acid 10% KET799 KET54 None None Arla solve 100%SRArl 0 citrate 6 1 0.003 0.009 Tolfenamic Superfine O.lM ""d acid 10% KETSOO KET54 None None Arla solve 100%SRArl 0 citrate 8 1 0.038 0.114 (") '"3 Tolfenamic Superfine O.lM s;;: acid 10% KET801 KET54 None None Arla solve 100%SRArl 0 citrate 0.5 2 0.002 0.006 Tolfenamic Superfine O.lM ~ N acid 10% KET802 KET54 None None Arla solve 100%SRArl 0 citrate 2 2 ----- 0 0 Tolfenamic Superfine O.lM ""' QC) acid 10% KET803 KET54 None None Arla solve 100%SRArl 0 citrate 4 2 0 -0 Tolfenamic Superfine O.lM 0 acid 10% KET804 KET54 None None Arla solve 100%SRArl 0 citrate 6 2 0.002 0.006 0 N Tolfenamic Superfine O.lM Ul acid 10% KET805 KET54 None None Arla solve 100%SRArl 0 citrate 8 2 0 Ul Tolfenamic Superfine 0.lM ~ acid 10% KET806 KET54 None None Arla solve 100%SRArl 0 citrate 0.5 3 0 0 Tolfenamic Superfine 0.lM N acid 10% Tolfenamic KET807 KET54 None None SArulap esorflivnee 100%SRArl 0 c0i.tlrMate 2 3 ---- 0 -"10", 0' acid 10% KET808 KET54 None None Arla solve 100%SRArl 0 citrate 4 3 0 ""' Tolfenamic Superfine 0.lM w""' acid 10% KET809 KET54 None None Arla solve 100%SRArl 0 citrate 6 3 0.004 0.012 0'I N Tolfenamic Superfine 0.lM Ul acid 10% KET810 KET54 None None Arlasolve 100%SRArl 0 citrate 8 3 0.002 0.006 Tolfenamic Crodamol STS- 0.lM acid 10% KET811 KET55 None None LQ(MH) 100% Crodamol 0 citrate 0.5 1 0.004 0.012 Tolfenamic Crodamol STS- 0.lM acid 10% KET812 KET55 None None LQ(MH) 100% Crodamol 0 citrate 2 1 0.018 0.054 Tolfenamic Crodamol STS- 0.lM acid 10% KET813 KET55 None None LQ(MH) 100% Crodamol 0 citrate 4 1 0.094 0.282 Tolfenamic Crodamol STS- 0.lM acid 10% KET814 KET55 None None LQ(MH) 100% Crodamol 0 citrate 6 1 0.002 0.006 en Tolfenamic Crodamol STS- 0.lM C acid 10% KET815 KET55 None None LQ(MH) 100% Crodamol 0 citrate 8 1 0.002 0.006 cr !!l.

Tolfenamic Crodamol STS- 0.lM e acid 10% KET816 KET55 None None LQ(MH) 100% Crodamol 0 citrate 0.5 2 ---- 0 ~ ro Tolfenamic Crodamol STS- 0.lM 0 en acid 10% KET817 KET55 None None LQ(MH) 100% Crodamol 0 citrate 2 2 0.003 0.009 "0 ' :;:,- Tolfenamic Crodamol STS- "' (I) 0.lM .u.., !2. acid 10% KET818 KET55 None None LQ(MH) 100% Crodamol 0 citrate 4 2 0.008 0.024~ ""'' ;a Tolfenamic Crodamol STS- 0.lM "' C acid 10% KET819 KETSS None None LQ(MH) 100% Crodamol 0 citrate 6 2 0.002 0.006 0 1D "' Tolfenamic Crodamol STS- 0.1M 0 N I acid 10% KET820 KET55 None None LQ(MH) 100% Crodamol 0 citrate 8 2 0.002 0.006 0 ;0o) "' Tolfenamic Crodamol STS- 0.lM ,_I . 0 acid 10% KET821 KET55 None None LQ(MH) 100% Crodamol 0 citrate 0.5 3 ---- 0 ,_. ► Tolfenamic Crodamol STS- 0.lM C acid 10% KET822 KET55 None None LQ(MH) 100% Crodamol 0 citrate 2 3 0.005 0.015 Tolfenamic Crodamol STS- 0.lM acid 10% KET823 KET55 None None LQ(MH) 100% Crodamol 0 citrate 4 3 ---- 0 Tolfenamic Crodamol STS- 0.lM acid 10% KET824 KET55 None None LQ(MH) 100% Crodamol 0 citrate 6 3 0.012 0.036 Tolfenamic Crodamol STS- 0.lM acid 10% KET825 KET55 None None LQ(MH) 100% Crodamol 0 citrate 8 3 ----- 0 Eucalyptus 0.lM Ketoprofen 10% KET826 KET56 Ethanol 50% Ethanol None None oil 21% 1,8-cineole citrate 0.5 1 0.004 0.012 Eucalyptus 0.1M ""d Ketoprofen 10% KET827 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 1 0.006 0.018 (") '"3 Eucalyptus 0.lM s;;: Ketoprofen 10% KET828 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 1 0.006 0.018 Eucalyptus 0.lM ~ N Ketoprofen 10% KET829 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 1 0.12 0.36 0 Eucalyptus 0.lM ""' QC) Ketoprofen 10% KET830 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 1 0.018 0.054 -0 Eucalyptus 0.lM 0 Ketoprofen 10% KET831 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 0.5 2 0.003 0.009 0 N Eucalyptus 0.lM Ul Ketoprofen 10% KET832 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 2 0.005 0,015 Ul Eucalyptus 0.lM ~ Ketoprofen 10% KET833 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 2 0.007 0.021 0 Eucalyptus 0.lM N Ketoprofen 10% KET834 KET56 Ethanol 50% Ethanol None None oEiul calyptus 21% 1,8 cineole c0i.tlrMate 6 2 0.011 0.033 -"10", 0' Ketoprofen 10% KET835 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 2 0.04 0.12 ""' Eucalyptus 0.1M w""' Ketoprofen 10% KET836 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 0.5 3 0.004 0.012 0'I N Eucalyptus 0.lM Ul Ketoprofen 10% KET837 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 3 0.006 0.018 Eucalyptus 0.lM Ketoprofen 10% KET838 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 3 0.007 0.021 Eucalyptus 0.lM Ketoprofen 10% KET839 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 3 0.015 0.045 Eucalyptus 0.lM Ketoprofen 10% KET840 KET56 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 3 0.071 0.213 Eucalyptus Ketoprofen 10% KET841 KET57 None None None None oil 70% 1,8-cineole None 0.5 1 0.005 0.D15 en Eucalyptus C Ketoprofen 10% KET842 KET57 None None None None oil 70% 1,8-cineole None 2 1 0.024 0.072 cr !!l.

Eucalyptus e Ketoprofen 10% KET843 KET57 None None None None oil 70% 1,8-cineole None 4 1 0.027 0.081 ~ ro Eucalyptus 0 en Ketoprofen 10% KET844 KET57 None None None None oil 70% 1,8-cineole None 6 1 0.121 0.363 "0 ' :;:,- Eucalyptus "' (I) .u.., !2.

Ketoprofen 10% KET845 KET57 None None None None oil 70% 1,8-cineole None 8 1 0.379 1.137 "0"'I' ""'' ;a Eucalyptus "' C Ketoprofen 10% KET846 KET57 None None None None oil 70% 1,8-cineole None 0.5 2 0.002 0.006 0 1D "' Eucalyptus 0 N I Ketoprofen 10% KET847 KET57 None None None None oil 70% 1,8-cineole None 2 2 0.002 0.006 0 ;0o) "' Eucalyptus ,.I . 0 Ketoprofen 10% KET848 KET57 None None None None oil 70% 1,8-cineole None 4 2 0.018 0.054 ,.. ► Eucalyptus C Ketoprofen 10% KET849 KET57 None None None None oil 70% 1,8-cineole None 6 2 0.11 0.33 Eucalyptus Ketoprofen 10% KET850 KET57 None None None None oil 70% 1,8-cineole None 8 2 0.406 1.218 Eucalyptus Ketoprofen 10% KET851 KET57 None None None None oil 70% 1,8-cineole None 0.5 3 0.002 0.006 Eucalyptus Ketoprofen 10% KET852 KET57 None None None None oil 70% 1,8-cineole None 2 3 0.005 0.D15 Eucalyptus Ketoprofen 10% KET853 KET57 None None None None oil 70% 1,8-cineole None 4 3 0.023 0.069 Eucalyptus ""d Ketoprofen 10% KET854 KET57 None None None None oil 70% 1,8-cineole None 6 3 0.06 0.18 (") '"3 Eucalyptus s;;: Ketoprofen 10% KET855 KET57 None None None None oil 70% 1,8-cineole None 8 3 0.178 0.534 ~ Ketoprofen 10% KET856 KET58 None None Propylene glycol 100% PPG None None None 0.5 1 0.004 0.012 N 0 ""' Ketoprofen 10% KET857 KET58 None None Propylene glycol 100% PPG None None None 2 1 0.003 0.009 -QC) 0 Ketoprofen 10% KET858 KET58 None None Propylene glycol 100% PPG None None None 4 1 0.004 0.012 0 N Ul Ketoprofen 10% KET859 KET58 None None Propylene glycol 100% PPG None None None 6 1 0.005 0.015 Ul ~ Ketoprofen 10% KET860 KET58 None None Propylene glycol 100% PPG None None None 8 1 0.021 0.063 0 N Ketoprofen 10% KET861 KET58 None None Propylene glycol 100% PPG None None None 0.5 2 0.01 0.03 0 ""' 1,0 Ketoprofen 10% KET862 KET58 None None Propylene glycol 100% PPG None None None 2 2 0.003 0.009 -""""'' Ketoprofen 10% KET863 KET58 None None Propylene glycol 100% PPG None None None 4 2 0.002 0.006 w 0'I N Ketoprofen 10% KET864 KET58 None None Propylene glycol 100% PPG None None None 6 2 0.004 0.012 Ul Ketoprofen 10% KET865 KET58 None None Propylene glycol 100%PPG None None None 8 2 0.019 0.057 Ketoprofen 10% KET866 KET58 None None Propylene glycol 100%PPG None None None 0.5 3 0.003 0.009 Ketoprofen 10% KET867 KET58 None None Propylene glycol 100% PPG None None None 2 3 0.002 0.006 Ketoprofen 10% KET868 KET58 None None Propylene glycol 100% PPG None None None 4 3 0.006 0.018 en Ketoprofen 10% KET869 KET58 None None Propylene glycol 100% PPG None None None 6 3 0.004 0.012 C cr Ketoprofen 10% KET870 KET58 None None Propylene glycol 100% PPG None None None 8 3 0.017 0.051 !!l. e 100% PPG-3 Benzyl ether ~ ro Ketoprofen 10% KET871 KET59 None None Crodamol-STS-LQ myristate None None None 0.5 1 0.003 0.009 0 en 100% PPG-3 Benzyl ether "0 ' :::, Ketoprofen 10% KET872 KET59 None None Crodamol-STS-LQ myristate None None None 2 1 0.004 0.012 "' (I) .u.., !2. 100% PPG-3 Benzyl ether 0'I "' ;a Ketoprofen 10% KET873 KET59 None None Crodamol-STS-LQ myristate None None None 4 1 0.008 0.024N "' 100% PPG-3 Benzyl ether "' C 0 1D Ketoprofen 10% KET874 KET59 None None Crodamol-STS-LQ myristate None None None 6 1 0.016 0.048 "' 0 N 100% PPG-3 Benzyl ether I ;0o) "' Ketoprofen 10% KET875 KET59 None None Crodamol-STS-LQ myristate None None None 8 1 0.109 0.327 ,_I . 0 100% PPG-3 Benzyl ether ,_. ► Ketoprofen 10% KET876 KET59 None None Crodamol-STS-LQ myristate None None None 0.5 2 0.004 0.012 C 100% PPG-3 Benzyl ether Ketoprofen 10% KET877 KET59 None None Crodamol-STS-LQ myristate None None None 2 2 0.006 0.Q18 100% PPG-3 Benzyl ether Ketoprofen 10% KET878 KET59 None None Crodamol-STS-LQ myristate None None None 4 2 0.007 0.021 100% PPG-3 Benzyl ether Ketoprofen 10% KET879 KET59 None None Crodamol-STS-LQ myristate None None None 6 2 0.D15 0.045 100% PPG-3 Benzyl ether Ketoprofen 10% KET880 KET59 None None Crodamol-STS-LQ myristate None None None 8 2 0.05 0.15 100% PPG-3 Benzyl ether Ketoprofen 10% KET881 KET59 None None Crodamol-STS-LQ myristate None None None 0.5 3 0.004 0.012 ""d 100% PPG-3 Benzyl ether (") Ketoprofen 10% KET882 KETS9 None None Crodamol-STS-LQ myristate None None None 2 3 0.003 0.009 '"3 100% PPG-3 Benzyl ether s;;: Ketoprofen 10% KET883 KET59 None None Crodamol-ST5-LQ myristate None None None 4 3 0.011 0.033 ~ 100% PPG-3 Benzyl ether N Ketoprofen 10% KET884 KET59 None None Crodamol-STS-LQ myristate None None None 6 3 0.006 0.Q18 ""' QC) 100% PPG-3 Benzyl ether - Ketoprofen 10% KET885 KET59 None None Crodamol-STS-LQ myristate None None None 8 3 0.025 0.075 Cromollient-SCE- 100% Di-PPG2-Myreth-10- 0 N Ketoprofen 10% KET886 KET60 None None LQ-(MH) Adipate None None None o.s 1 0.006 0.D18 Ul Ul Ketoprofen 10% KET887 KET60 None None Cromollient-SCE- 100% Di-PPG2-Myreth-10- None None None 2 1 0.021 0.063 LQ-(MH) Adi pate ~ Cromollient-SCE- 100% Di-PPG2-Myreth-10- N Ketoprofen 10% KET888 KET60 None None LQ-(MH) Adipate None None None 4 1 0.028 0.084 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- -"1",0' Ketoprofen 10% KET889 KET60 None None LQ-(MH) Adipate None None None 6 1 0.037 0.111 ""' Cromollient-SCE- 100% Di-PPG2-Myreth-10- w""' Ketoprofen 10% KET890 KET60 None None LQ-(MH) Adipate None None None 8 1 0.06 0.18 0'I N Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ul Ketoprofen 10% KET891 KET60 None None LQ-(MH) Adipate None None None 0.5 2 0.006 0.D18 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ketoprofen 10% KET892 KET60 None None LQ-(MH) Adipate None None None 2 2 0.008 0.024 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ketoprofen 10% KET893 KET60 None None LQ-(MH) Adipate None None None 4 2 0.008 0.024 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ketoprofen 10% KET894 KET60 None None LQ-(MH) Adipate None None None 6 2 0.017 0.051 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ketoprofen 10% KET895 KET60 None None LQ-(MH) Adipate None None None 8 2 0.038 0.114 en Cromollient-SCE- 100% Di-PPG2-Myreth-10- C Ketoprofen 10% KET896 KET60 None None LQ-(MH) Adipate None None None 0.5 3 0.006 0.018 cr Cromollient-SCE- 100% Di-PPG2-Myreth-10- !!l. e Ketoprofen 10% KET897 KET60 None None LQ-(MH) Adipate None None None 2 3 0.005 0.015 ~ ro Cromollient-SCE- 100% Di-PPG2-Myreth-10- 0 en Ketoprofen 10% KET898 KET60 None None LQ-(MH) Adipate None None None 4 3 0.007 0.021 "0 ' :::, Cromollient-SCE- 100% Di-PPG2-Myreth-10- "' (I) .u.., !2.

Ketoprofen 10% KET899 KET60 None None LQ-(MH) Adipate None None None 6 3 0.011 0.033 w0'I ""'' ;a Cromollient-SCE- 100% Di-PPG2-Myreth-10- "' C Ketoprofen 10% KET900 KET60 None None LQ-(MH) Adipate None None None 8 3 0.018 0.054 0 1D Eucalyptus 0.lM "0 ' N I Flunixin 10% KET901 KET61 Ethanol 50% Ethanol None None oil 21% 1,8-cineole citrate 0.5 1 0.006 0.D18 0 ;0o) "' Eucalyptus 0.lM ,.I . 0 Flunixin 10% KET902 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 1 0.005 0.D15 ,.. ► Eucalyptus 0.lM C Flunixin 10% KET903 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 1 0.007 0.021 Eucalyptus 0.lM Flunixin 10% KET904 KET61 Ethanol 50% Ethanol None None oil 21% 118 cineole citrate 6 1 0.01 0.03 Eucalyptus 0.lM Flunixin 10% KET905 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 1 0.039 0.117 Eucalyptus 0.lM Flunixin 10% KET906 KET61 Ethanol 50% Ethanol None None oil 21% 118 cineole citrate 0.5 2 0.008 0.024 Eucalyptus 0.lM Flunixin 10% KET907 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 2 0.007 0.021 Eucalyptus 0.lM ""d Flunixin 10% KET908 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 2 0.006 0.018 (") Eucalyptus 0.lM '"3 Flunixin 10% KET909 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 2 0.218 0.654 s;;: Eucalyptus 0.lM ~ N Flunixin 10% KET910 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 2 0.008 0.024 0 Eucalyptus 0.lM ""' QC) Flunixin 10% KET911 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 3 0.009 0.027 -0 Eucalyptus 0.1M 0 Flunixin 10% KET912 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 0.5 3 ---- 0 0 N Eucalyptus 0.lM Ul Flunixin 10% KET913 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 3 0.005 0.QlS Ul Eucalyptus O.lM ~ Flunixin 10% KET914 KET61 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 3 0.008 0.024 0 Eucalyptus O.lM N Flunixin 10% KET915 KET61 Ethanol 50% Ethanol None None oEiul calyptus 21% 1,8 cineole citrate 8 3 0.014 0.042 -"10", 0' Flunixin 10% KET916 KET62 None None None None oil 70% 1,8-cineole None 2 1 0.005 0.015 ""' Eucalyptus w""' Flunixin 10% KET917 KET62 None None None None oil 70% 1,8-cineole None 4 1 0.005 0.015 0'I N Eucalyptus Ul Flunixin 10% KET918 KET62 None None None None oil 70% 1,8-cineole None 0.5 1 0 Eucalyptus Flunixin 10% KET919 KET62 None None None None oil 70% 1,8-cineole None 6 1 0.251 0.753 Eucalyptus Flunixin 10% KET920 KET62 None None None None oil 70% 1,8-cineole None 8 1 2.775 8.325 Eucalyptus Flunixin 10% KET921 KET62 None None None None oil 70% 1,8-cineole None 2 2 0.009 0.027 Eucalyptus Flunixin 10% KET922 KET62 None None None None oil 70% 1,8-cineole None 4 2 0.017 0.051 en Eucalyptus C Flunixin 10% KET923 KET62 None None None None oil 70% 1,8-cineole None 0.5 2 ---- 0 cr !!l.

Eucalyptus e Flunixin 10% KET924 KET62 None None None None oil 70% 1,8-cineole None 6 2 0.044 0.132 ~ ro Eucalyptus 0 en Flunixin 10% KET925 KET62 None None None None oil 70% 1,8-cineole None 8 2 1.094 3.282 "0 ' :::, Eucalyptus "' (I) .u.., !2.

Flunixin 10% KET926 KET62 None None None None oil 70% 1,8-cineole None 6 3 00"""1' ""'' ;a Eucalyptus "' C Flunixin 10% KET927 KET62 None None None None oil 70% 1,8-cineole None 8 3 0.056 0.168 0 1D "' Eucalyptus 0 N I Flunixin 10% KET928 KET62 None None None None oil 70% 1,8-cineole None 4 3 0 0 ;0o) "' Eucalyptus ,.I . 0 Flunixin 10% KET929 KET62 None None None None oil 70% 1,8-cineole None 2 3 ---- 0 ,.. ► Eucalyptus C Flunixin 10% KET930 KET62 None None None None oil 70% 1,8-cineole None 0.5 3 ---- 0 Flunixin 10% KET931 KET63 None None Propylene glycol 100% PPG None None None 0.5 1 0 Flunixin 10% KET932 KET63 None None Propylene glycol 100% PPG None None None 8 1 0.208 0.624 Flunixin 10% KET933 KET63 None None Propylene glycol 100% PPG None None None 2 1 0 Flunixin 10% KET934 KET63 None None Propylene glycol 100% PPG None None None 4 1 0.012 0.036 Flunixin 10% KET935 KET63 None None Propylene glycol 100% PPG ""d None None None 6 1 0 (") '"3 Flunixin 10% KET936 KET63 None None Propylene glycol 100% PPG None None None 6 2 0.009 0.027 s;;: Flunixin 10% KET937 KET63 None None Propylene glycol 100% PPG None None None 4 2 0.006 0.018 ~ N Flunixin 10% KET938 KET63 None None Propylene glycol 100% PPG None None None 0.5 2 ---- 0 -"Q"C') 0 Flunixin 10% KET939 KET63 None None Propylene glycol 100% PPG None None None 2 2 0.006 0.018 0 N Flunixin 10% KET940 KET63 None None Propylene glycol 100% PPG None None None 8 2 0.012 0.036 Ul Ul ~ Flunixin 10% KET941 KET63 None None Propylene glycol 100% PPG None None None 8 3 0.006 0.018 0 N Flunixin 10% KET942 KET63 None None Propylene glycol 100% PPG None None None 6 3 0.009 0.027 0 ""' 1,0 Flunixin 10% KET943 KET63 None None Propylene glycol 100% PPG None None None 4 3 0.006 0.018 -""""'' Flunixin 10% KET944 KET63 None None Propylene glycol 100% PPG None None None 2 3 0.006 0.Q18 w 0'I N Flunixin 10% KET945 KET63 None None Propylene glycol 100% PPG None None None 0.5 3 0 Ul 100% PPG-3 Benzyl ether Flunixin 10% KET946 KET64 None None Crodamol-STS-LQ myristate None None None 8 1 0.018 0.054 100% PPG-3 Benzyl ether Flunixin 10% KET947 KET64 None None Crodamol-STS-LQ myristate None None None 6 1 0.006 0.018 100% PPG-3 Benzyl ether Flunixin 10% KET948 KET64 None None Crodamol-STS-LQ myristate None None None 4 1 0.005 0.015 100% PPG-3 Benzyl ether Flunixin 10% KET949 KET64 None None Crodamol-STS-LQ myristate None None None 2 1 ---- 0 100% PPG-3 Benzyl ether en Flunixin 10% KET950 KET64 None None Crodamol-STS-LQ myristate None None None 0.5 1 0.006 0.018 C cr 100% PPG-3 Benzyl ether !!l.

Flunixin 10% KET951 KET64 None None Crodamol-STS-LQ myristate None None None 0.5 2 0.007 0.021 e ~ 100% PPG-3 Benzyl ether ro 0 en Flunixin 10% KET952 KET64 None None Crodamol-STS-LQ myristate None None None 2 2 0.005 0.015 "' 100% PPG-3 Benzyl ether ::J" "' (I) Flunixin 10% KET953 KET64 None None Crodamol-STS-LQ myristate None None None 4 2 0 0'I .u.., !2. 100% PPG-3 Benzyl ether Ul ""'' ;a Flunixin 10% KET954 KET64 None None Crodamol-STS-LQ myristate None None None 6 2 0.006 0.018 "' C 0 1D 100% PPG-3 Benzyl ether "' 0 N Flunixin 10% KET955 KET64 None None Crodamol-STS-LQ myristate None None None 8 2 0 I ;0o) 100% PPG-3 Benzyl ether "' I Flunixin 10% KET956 KET64 None None Crodamol-STS-LQ myristate None None None 0.5 3 0 ,... 0 ,... ► 100% PPG-3 Benzyl ether C Flunixin 10% KET957 KET64 None None Crodamol-STS-LQ myristate None None None 2 3 ---- 0 100% PPG-3 Benzyl ether Flunixin 10% KET958 KET64 None None Crodamol-STS-LQ myristate None None None 4 3 ---- 0 100% PPG-3 Benzyl ether Flunixin 10% KET959 KET64 None None Crodamol-STS-LQ myristate None None None 6 3 0.006 0.Q18 100% PPG-3 Benzyl ether Flunixin 10% KET960 KET64 None None Crodamol-STS-LQ myristate None None None 8 3 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Flunixin 10% KET961 KET65 None None LQ-(MH) Adipate None None None 0.5 1 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- ""d Flunixin 10% KET962 KET65 None None LQ-(MH) Adipate None None None 2 1 0 (") Cromollient-SCE- 100% Di-PPG2-Myreth-10- '"3 Flunixin 10% KET963 KET65 None None LQ-(MH) Adipate None None None 6 1 0.006 0.Q18 s;;: Cromollient-SCE- 100% Di-PPG2-Myreth-10- ~ Flunixin 10% KET964 KET65 None None LQ-(MH) Adipate None None None 4 1 0 N Cromollient-SCE- 100% Di-PPG2-Myreth-10- 0 ""' Flunixin 10% KET965 KET65 None None LQ-(MH) Adipate None None None 8 1 0.008 0.024 -QC) Cromollient-SCE- 100% Di-PPG2-Myreth-10- 0 Flunixin 10% KET966 KET65 None None LQ-(MH) Adipate None None None 6 2 0.007 0.021 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- N Ul Flunixin 10% KET967 KET65 None None LQ-(MH) Adipate None None None 2 2 ---- 0 Ul Cromollient-SCE- 100% Di-PPG2-Myreth-10- ~ Flunixin 10% KET968 KET65 None None LQ-{MH) Adipate None None None 8 2 0.02 0.06 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- N Flunixin 10% KET969 KET65 None None CLQro-m{MoHlli)e nt-SCE- A10d0ip%a tDe i-PPG2-Myreth-10- None None None 0.5 2 ---- 0 -"10", 0' Flunixin 10% KET970 KET65 None None LQ-{MH) Adipate None None None 4 2 0.006 0.D18 ""' Cromollient-SCE- 100% Di-PPG2-Myreth-10- w""' Flunixin 10% KET971 KET65 None None LQ-{MH) Adipate None None None 4 3 0.005 0.015 0'I N Cromollient-SCE- 100% Di-PPG2-Myreth-10- Ul Flunixin 10% KET972 KET65 None None LQ-{MH) Adipate None None None 6 3 0.005 0.015 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Flunixin 10% KET973 KET65 None None LQ-{MH) Adipate None None None 8 3 0.006 0.018 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Flunixin 10% KET974 KET65 None None LQ-{MH) Adipate None None None 2 3 0 Cromollient-SCE- 100% Di-PPG2-Myreth-10- Flunixin 10% KET975 KET65 None None LQ-{MH) Adipate None None None 0.5 3 ---- 0 Tolfenamic Eucalyptus 0.lM acid 10% KET976 KET66 Ethanol 50% Ethanol None None oil 21% 1,8-cineole citrate 0.5 1 0.004 0.012 en Tolfenamic Eucalyptus 0.lM C acid 10% KET977 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 1 0.009 0.027 cr !!l.

Tolfenamic Eucalyptus 0.lM e acid 10% KET978 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 1 0.01 0.03 ~ ro Tolfenamic Eucalyptus 0.lM 0 en acid 10% KET979 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 1 0.015 0.045 "0 ' :::, Tolfenamic Eucalyptus "' (I) 0.lM .u.., !2. acid 10% KET980 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 1 0.006 0.Q18~ ""'' ;a Tolfenamic Eucalyptus 0.lM "' C acid 10% KET981 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 0.5 2 0 0 1D "' Tolfenamic Eucalyptus 0.lM 0 N I acid 10% KET982 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 2 0.004 0.012 0 ;0o) "' Tolfenamic Eucalyptus 0.lM ,.I . 0 acid 10% KET983 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 2 0.003 0.009 ,.. ► Tolfenamic Eucalyptus 0.lM C acid 10% KET984 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 2 0.005 0.D15 Tolfenamic Eucalyptus 0.lM acid 10% KET985 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 2 0.002 0.006 Tolfenamic Eucalyptus 0.lM acid 10% KET986 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 0.5 3 0.004 0.012 Tolfenamic Eucalyptus 0.lM acid 10% KET987 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 2 3 0.004 0.012 Tolfenamic Eucalyptus 0.lM acid 10% KET988 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 4 3 0.009 0.027 Tolfenamic Eucalyptus 0.lM ""d acid 10% KET989 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 6 3 0.005 0.015 (") '"3 Tolfenamic Eucalyptus 0.lM s;;: acid 10% KET990 KET66 Ethanol 50% Ethanol None None oil 21% 1,8 cineole citrate 8 3 0.003 0.009 Tolfenamic Eucalyptus ~ N acid 10% KET991 KET67 None None None None oil 70% 1,8-cineole None 0.5 1 0.005 0.D15 0 Tolfenamic Eucalyptus ""' QC) acid 10% KET992 KET67 None None None None oil 70% 1,8-cineole None 2 1 0.007 0.021 -0 Tolfenamic Eucalyptus 0 acid 10% KET993 KET67 None None None None oil 70% 1,8-cineole None 4 1 0.01 0.03 0 N Tolfenamic Eucalyptus Ul acid 10% KET994 KET67 None None None None oil 70% 1,8-cineole None 6 1 0.006 0.Q18 Ul Tolfenamic Eucalyptus ~ acid 10% KET995 KET67 None None None None oil 70% 1,8-cineole None 8 1 0.006 0.018 0 Tolfenamic Eucalyptus N acid 10% Tolfenamic KET996 KET67 None None None None oEiul calyptus 70% 1,8-cineole None 0.5 2 ---- 0 -"10", 0' acid 10% KET997 KET67 None None None None oil 70% 1,8-cineole None 2 2 0.003 0.009 ""' Tolfenamic Eucalyptus w""' acid 10% KET998 KET67 None None None None oil 70% 1,8-cineole None 4 2 0.005 0.015 0'I N Tolfenamic Eucalyptus Ul acid 10% KET999 KET67 None None None None oil 70% 1,8-cineole None 6 2 0.005 0.015 Tolfenamic KETlOO Eucalyptus acid 10% 0 KET67 None None None None oil 70% 1,8-cineole None 8 2 0.005 0.015 Tolfenamic KETlOO Eucalyptus acid 10% 1 KET67 None None None None oil 70% 1,8-cineole None 0.5 3 0.003 0.009 Tolfenamic KETlOO Eucalyptus acid 10% 2 KET67 None None None None oil 70% 1,8-cineole None 2 3 0.002 0.006 Tolfenamic KETlOO Eucalyptus acid 10% 3 KET67 None None None None oil 70% 1,8-cineole None 4 3 0.005 0.015 en Tolfenamic KETlOO Eucalyptus C acid 10% 4 KET67 None None None None oil 70% 1,8-cineole None 6 3 0.008 0.024 cr !!l.

Tolfenamic KETlOO Eucalyptus e acid 10% 5 KET67 None None None None oil 70% 1,8-cineole None 8 3 0.004 0.012 ~ ro Tolfenamic KETlOO 0 en acid 10% 6 KET68 None None Propylene glycol 100% PPG None None None 0.5 1 0.002 0.006 "0 ' :;:,- Tolfenamic "' (I) KETlOO .u.., !2. acid 10% 7 KET68 None None Propylene glycol 100% PPG None None None 2 1 0.005 0.015~ ""'' ;a Tolfenamic KETlOO "' C acid 10% 8 KET68 None None Propylene glycol 100% PPG None None None 4 1 0.007 0.021 0 1D "' Tolfenamic KETlOO 0 N I acid 10% 9 KET68 None None Propylene glycol 100% PPG None None None 6 1 0 0 ;0o) "' Tolfenamic KET101 ,.I . 0 acid 10% 0 KET68 None None Propylene glycol 100% PPG None None None 8 1 0.002 0.006 ,.. ► Tolfenamic KET101 C acid 10% 1 KET68 None None Propylene glycol 100% PPG None None None 0.5 2 ---- 0 Tolfenamic KET101 acid 10% 2 KET68 None None Propylene glycol 100% PPG None None None 2 2 0.002 0.006 Tolfenamic KET101 acid 10% 3 KET68 None None Propylene glycol 100% PPG None None None 4 2 0.004 0.012 Tolfenamic KET101 acid 10% 4 KET68 None None Propylene glycol 100% PPG None None None 6 2 0.002 0.006 Tolfenamic KET101 acid 10% 5 KET68 None None Propylene glycol 100% PPG None None None 8 2 0.005 0.015 Tolfenamic KET101 ""d acid 10% 6 KET68 None None Propylene glycol 100% PPG None None None 0.5 3 0.005 0.015 (") '"3 Tolfenamic KET101 s;;: acid 10% 7 KET68 None None Propylene glycol 100% PPG None None None 2 3 0.012 0.036 Tolfenamic KET101 ~ N acid 10% 8 KET68 None None Propylene glycol 100% PPG None None None 4 3 0.006 0.018 0 Tolfenamic KET101 ""' QC) acid 10% 9 KET68 None None Propylene glycol 100% PPG None None None 6 3 0.008 0.024 -0 Tolfenamic KET102 0 acid 10% 0 KET68 None None Propylene glycol 100% PPG None None None 8 3 0.002 0.006 0 N Tolfenamic KET102 100% PPG-3 Benzyl ether Ul acid 10% 1 KET69 None None Crodamol-STS-LQ myristate None None None 0.5 1 0 Ul Tolfenamic KET102 100% PPG-3 Benzyl ether ~ acid 10% 2 KET69 None None Crodamol-STS-LQ myristate None None None 2 1 0 0 Tolfenamic KET102 100% PPG-3 Benzyl ether N acid 10% 3 KET69 None Tolfenamic KET102 None Crodamol-STS-LQ 1m0y0r%is tPaPteG -3 Benzyl ether None None None 4 1 0.006 0,018 -"10", 0' acid 10% 4 KET69 None None Crodamol-STS-LQ myristate None None None 6 1 0.016 0.048 ""' Tolfenamic KET102 100% PPG-3 Benzyl ether w""' acid 10% 5 KET69 None None Crodamol-STS-LQ myristate None None None 8 1 0.012 0.036 0'I N Tolfenamic KET102 100% PPG-3 Benzyl ether Ul acid 10% 6 KET69 None None Crodamol-STS-LQ myristate None None None 0.5 2 0.01 0.03 Tolfenamic KET102 100% PPG-3 Benzyl ether acid 10% 7 KET69 None None Crodamol-STS-LQ myristate None None None 2 2 0.017 0.051 Tolfenamic KET102 100% PPG-3 Benzyl ether acid 10% 8 KET69 None None Crodamol-STS-LQ myristate None None None 4 2 0.004 0.012 Tolfenamic KET102 100% PPG-3 Benzyl ether acid 10% 9 KET69 None None Crodamol-STS-LQ myristate None None None 6 2 0.005 0,015 Tolfenamic KET103 100% PPG-3 Benzyl ether acid 10% 0 KET69 None None Crodamol-STS-LQ myristate None None None 8 2 0.003 0.009 en Tolfenamic KET103 100% PPG-3 Benzyl ether C acid 10% 1 KET69 None None Crodamol-STS-LQ myristate None None None 0.5 3 0.003 0.009 cr !!l.

Tolfenamic KET103 100% PPG-3 Benzyl ether e acid 10% 2 KET69 None None Crodamol-STS-LQ myristate None None None 2 3 0.002 0.006 ~ ro Tolfenamic KET103 100% PPG-3 Benzyl ether 0 en acid 10% 3 KET69 None None Crodamol-STS-LQ myristate None None None 4 3 0.005 0.015 "0 ' :;:,- Tolfenamic 100% PPG-3 Benzyl ether "' (I) KET103 .u.., !2. acid 10% 4 KET69 None None Crodamol-STS-LQ myristate None None None 6 3 0.003 0.009~ ""'' ;a Tolfenamic KET103 100% PPG-3 Benzyl ether "' C acid 10% 5 KET69 None None Crodamol-STS-LQ myristate None None None 8 3 0.003 0.009 0 1D "' Tolfenamic KET103 Cromollient-SCE- 100% Di-PPG2-Myreth-1D- 0 N I acid 10% 6 KET70 None None LQ-(MH) Adipate None None None 0.5 1 0.007 0.021 0 ;0o) "' Tolfenamic KET103 Cromollient-5CE- 100% Di-PPG2-Myreth-10- ,.I . 0 acid 10% 7 KET70 None None LQ-(MH) Adipate None None None 2 1 0.003 0.009 ,.. ► Tolfenamic KET103 Cromollient-SCE- 100% Di-PPG2-Myreth-1DC acid 10% 8 KET70 None None LQ-(MH) Adipate None None None 4 1 0.008 0.024 Tolfenamic KET103 Cromollient-SCE- 100% Di-PPG2-Myreth-1Dacid 10% 9 KET70 None None LQ-(MH) Adipate None None None 6 1 0.004 0.012 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-1Dacid 10% 0 KET70 None None LQ-(MH) Adipate None None None 8 1 ---- 0 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-1Dacid 10% 1 KET70 None None LQ-(MH) Adipate None None None 0.5 2 0.004 0.012 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-10- acid 10% 2 KET70 None None LQ-(MH) Adipate None None None 2 2 0.009 0.027 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-10- ""d acid 10% 3 KET70 None None LQ-(MH) Adipate None None None 4 2 0.006 0.018 (") '"3 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPGZ-Myreth-10- s;;: acid 10% 4 KET70 None None LQ-(MH) Adipate None None None 6 2 0.012 0.036 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-1D- ~ N acid 10% 5 KET70 None None LQ-(MH) Adipate None None None 8 2 0.008 0.024 0 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPGZ-Myreth-10- ""' QC) acid 10% 6 KET70 None None LQ-(MH) Adipate None None None 0.5 3 0 -0 Tolfenamic KET104 Cromollient-SCE- 100% Di-PPGZ-Myreth-10- 0 acid 10% 7 KET70 None None LQ-(MH) Adipate None None None 2 3 0.003 0.009 0 N Tolfenamic KET104 Cromollient-SCE- 100% Di-PPGZ-Myreth-10- Ul acid 10% 8 KET70 None None LQ-(MH) Adipate None None None 4 3 0.005 0,015 Ul Tolfenamic KET104 Cromollient-SCE- 100% Di-PPG2-Myreth-10- ~ acid 10% 9 KET70 None None LQ-{MH) Adipate None None None 6 3 0.003 0.009 0 Tolfenamic KET105 Cromollient-SCE- 100% Di-PPG2-Myreth-10- N acid 10% 0K ET105 KET70 None None 1LQ-E-t{hMyHl-2) - Adipate None None None 8 3 0.002 0.006 -"10", 0' Ketoprofen 10% 1 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol 50ng/ml None 0.5 1 0.029 0.087 ""' KET105 1-Ethyl-2- w""' Ketoprofen 10% 2 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 2 1 0.033 0.099 0'I N KET105 1-Ethyl-2- Ul Ketoprofen 10% 3 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 4 1 0.007 0.021 KET105 1-Ethyl-2- Ketoprofen 10% 4 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 6 1 0.013 0.039 KET105 1-Ethyl-2- Ketoprofen 10% s KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 8 1 0.024 0.072 KET105 1-Ethyl-2- Ketoprofen 10% 6 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol 50ng/ml None 0.5 2 0.025 0.075 KET105 1-Ethyl-2- Ketoprofen 10% 7 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 2 2 0.023 0.069 en KET105 Hthyl-2- C Ketoprofen 10% 8 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol 50ng/ml None 4 2 0.007 0.021 cr !!l. KET105 Hthyl-2- e Ketoprofen 10% 9 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 6 2 0.007 0.021 ~ ro KET106 Hthyl-2- 0 en Ketoprofen 10% 0 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 8 2 0.01 0.03 "0 ' :::, 1-Ethyl-2- "' (I) KET106 .u.., !2.

Ketoprofen 10% 1 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 3 0.022 0.066~ ""'' ;a KET106 1-Ethyl-2- "' C Ketoprofen 10% 2 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 2 3 0.057 0.171 0 1D "' KET106 1-Ethyl-2- 0 N I Ketoprofen 10% 3 KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 4 3 0.016 0.048 0 ;0o) "' KET106 1-Ethyl-2- ,.I . 0 Ketoprofen 10% 4 KET71 Ethanol 50% EthOH Pryrrolidone 4S%EP Menthol SOng/ml None 6 3 0.011 0.033 ,.. ► KET106 Hthyl-2- C Ketoprofen 10% s KET71 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 8 3 0.059 0.177 KET106 Ketoprofen 10% 6 KET72 Ethanol 50% EthOH Propylene glycol 4S% PPG Menthol song/ml None 0.5 1 0.009 0.027 KET106 Ketoprofen 10% 7 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 2 1 0.007 0.021 KET106 Ketoprofen 10% 8 KET72 Ethanol SO% EthOH Propylene glycol 45% PPG Menthol song/ml None 4 1 0.017 0.051 KET106 Ketoprofen 10% 9 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 6 1 0.034 0.102 KET107 ""d Ketoprofen 10% 0 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 8 1 0.033 0.099 (") '"3 KET107 s;;: Ketoprofen 10% 1 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol SOng/ml None 0.5 2 0.013 0.039 KET107 ~ N Ketoprofen 10% 2 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol SOng/ml None 2 2 0.045 0.135 0 KET107 ""' QC) Ketoprofen 10% 3 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol SOng/ml None 4 2 0.047 0.141 -0 KET107 0 Ketoprofen 10% 4 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 6 2 0.053 0.159 0 N KET107 Ul Ketoprofen 10% s KET72 Ethanol 50% EthOH Propylene glycol 4S% PPG Menthol song/ml None 8 2 0.086 0.258 Ul KET107 ~ Ketoprofen 10% 6 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 0.5 3 0.017 0.051 0 KET107 N Ketoprofen 10% 7 KET107 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 2 3 0.075 0.225 -"10", 0' Ketoprofen 10% 8 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol SOng/ml None 4 3 0.083 0.249 """"'' KET107 w Ketoprofen 10% 9 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 6 3 0.089 0.267 0'I N KET108 Ul Ketoprofen 10% 0 KET72 Ethanol 50% EthOH Propylene glycol 45% PPG Menthol song/ml None 8 3 0.107 0.321 KET108 Ketoprofen 10% 1 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 0.5 1 0.035 0.105 KET108 Ketoprofen 10% 2 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 2 1 0.042 0.126 KET108 Ketoprofen 10% 3 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 4 1 0.04 0.12 KET108 Ketoprofen 10% 4 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 6 1 0.051 0.153 en KET108 C Ketoprofen 10% 5 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 8 1 0.048 0.144 cr !!l. KET108 e Ketoprofen 10% 6 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 0.5 2 0.029 0.087 ~ ro KET108 0 en Ketoprofen 10% 7 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 2 2 0.024 0.072 "0 ' :::, "' (I) KET108 .u.., !2.

Ketoprofen 10% 8 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 4 2 0.032 0.096~ ""'' ;a KET108 "' C Ketoprofen 10% 9 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol 50ng/ml None 6 2 0.034 0.102 0 1D "' KET109 0 N I Ketoprofen 10% 0 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 8 2 0.062 0.186 0 ;0o) "' KET109 ,.I . 0 Ketoprofen 10% 1 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 0.5 3 0.018 0.054 ,.. ► KET109 C Ketoprofen 10% 2 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 2 3 0.025 0.075 KET109 Ketoprofen 10% 3 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 4 3 0.025 0.075 KET109 Ketoprofen 10% 4 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 6 3 0.057 0.171 KET109 Ketoprofen 10% 5 KET73 Ethanol 50% EthOH lsomyristate 45% ISOMYR Menthol song/ml None 8 3 0.874 2.622 KET109 Ketoprofen 10% 6 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 0.5 1 0.006 0.018 KET109 ""d Ketoprofen 10% 7 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 2 1 0.026 0.078 (") '"3 KET109 s;;: Ketoprofen 10% 8 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol SOng/ml None 4 1 0.032 0.096 KET109 ~ N Ketoprofen 10% 9 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol SOng/ml None 6 1 0.031 0.093 0 KETllO ""' QC) Ketoprofen 10% 0 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol SOng/ml None 8 1 0.037 0.111 -0 KET110 0 Ketoprofen 10% 1 KET74 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml None 0.5 2 0.025 0.075 0 N KETllO Ul Ketoprofen 10% 2 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 2 2 0.029 0.087 Ul KETllO ~ Ketoprofen 10% 3 KET74 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml None 4 2 0.033 0.099 0 KETllO N Ketoprofen 10% 4K ETllO KET74 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml None 6 2 0.038 0.114 -"10", 0' Ketoprofen 10% 5 KET74 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol SOng/ml None 8 2 0.057 0.171 """"'' KETllO w Ketoprofen 10% 6 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 0.5 3 0.015 0.045 0'I N KETllO Ul Ketoprofen 10% 7 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 2 3 0.018 0.054 KETllO Ketoprofen 10% 8 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 4 3 0.54 1.62 KETllO Ketoprofen 10% 9 KET74 Ethanol 50% EthOH Oleyl alcohol 45%0A Menthol song/ml None 6 3 1.309 3.927 KET111 Ketoprofen 10% 0 KET74 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml None 8 3 3.433 10.299 KETlll Ketoprofen 10% 1 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 0.5 1 0.015 0.045 en KETlll C Ketoprofen 10% 2 KET75 lsopronanol 50% IPN Oley! alcohol 45%0A Menthol song/ml None 2 1 0.033 0.099 cr !!l. KETlll e Ketoprofen 10% 3 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 4 1 0.033 0.099 ~ ro KETlll 0 en Ketoprofen 10% 4 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 6 1 0.052 0.156 "0 ' :::, "' (I) KET111 .u.., !2.

Ketoprofen 10% 5 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 8 1 0.051 0.153"-"-l' ""'' ;a KETlll "' C Ketoprofen 10% 6 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol SOng/ml None 0.5 2 0.041 0.123 0 1D "' KET111 0 N I Ketoprofen 10% 7 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 2 2 0.037 0.111 0 ;0o) "' KETlll ,.I . 0 Ketoprofen 10% 8 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 4 2 0.037 0.111 ,.. ► KETlll C Ketoprofen 10% 9 KET75 lsopronanol 50% IPN Oley! alcohol 45%0A Menthol song/ml None 6 2 0.042 0.126 KET112 Ketoprofen 10% 0 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 8 2 0.041 0.123 KET112 Ketoprofen 10% 1 KET75 lsopronanol 50% IPN Oley! alcohol 45%0A Menthol song/ml None 0.5 3 0.036 0.108 KET112 Ketoprofen 10% 2 KET75 lsopronanol 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 2 3 0.032 0.096 KET112 Ketoprofen 10% 3 KET75 lsopronano! 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 4 3 0.062 0.186 KET112 ""d Ketoprofen 10% 4 KET75 lsopronano! 50% IPN Oleyl alcohol 45%0A Menthol song/ml None 6 3 0.159 0.477 (") '"3 KET112 s;;: Ketoprofen 10% 5 KET75 lsopronano! 50% IPN Oleyl alcohol 45%0A Menthol SOng/ml None 8 3 0.315 0.945 KET112 1-Ethyl-2- Eucalyptus ~ N Ketoprofen 10% 6 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 0.5 1 0.033 0.099 0 KET112 1-Ethyl-2- Eucalyptus ""' QC) Ketoprofen 10% 7 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 1 0.038 0.114 -0 KET112 1-Ethyl-2- Eucalyptus 0 Ketoprofen 10% 8 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 1 0.044 0.132 0 N KET112 1-Ethyl-2- Eucalyptus Ul Ketoprofen 10% 9 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 1 0.241 0.723 Ul KET113 1-Ethyl-2- Eucalyptus ~ Ketoprofen 10% 0 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 1 0.597 1.791 0 KET113 1-Ethyl-2- Eucalyptus N Ketoprofen 10% 1 KET76 KET113 Ethanol 50% EthOH 1P-rEyrthroylli-d2o-ne 45%EP oEiul calyptus 3.5% 1,8-cineole None 0.5 2 0.021 0.063 -"10", 0' Ketoprofen 10% 2 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 2 0.072 0.216 ""' KET113 1-Ethyl-2- Eucalyptus w""' Ketoprofen 10% 3 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 2 0.09 0.27 0'I N KET113 1-Ethyl-2- Eucalyptus Ul Ketoprofen 10% 4 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 2 0.092 0.276 KET113 l-Ethyl-2- Eucalyptus Ketoprofen 10% 5 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 2 0.099 0.297 KET113 1-Ethyl-2- Eucalyptus Ketoprofen 10% 6 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 0.5 3 0.041 0.123 KET113 1-Ethyl-2- Eucalyptus Ketoprofen 10% 7 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 3 0.034 0.102 KET113 1-Ethyl-2- Eucalyptus Ketoprofen 10% 8 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 3 0.679 2.037 en KET113 1-Ethyl-2- Eucalyptus C Ketoprofen 10% 9 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 3 4.982 14.946 cr !!l. KET114 1-Ethyl-2- Eucalyptus e Ketoprofen 10% 0 KET76 Ethanol 50% EthOH Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 3 10.669 32.007 ~ ro KET114 Eucalyptus 0 en Ketoprofen 10% 1 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0.085 0.255 "0 ' :::, Eucalyptus "' (I) KET114 u, !2.

Ketoprofen 10% 2 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.1 0.3~ """' ;a KET114 Eucalyptus "' "' C Ketoprofen 10% 3 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 1 0.12 0.36 0 1D "' KET114 Eucalyptus 0 N I Ketoprofen 10% 4 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 1 0.069 0.207 0 ;0o) "' KET114 Eucalyptus ,.I . 0 Ketoprofen 10% 5 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 1 0.085 0.255 ,.. ► KET114 Eucalyptus C Ketoprofen 10% 6 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 2 0.008 0.024 KET114 Eucalyptus Ketoprofen 10% 7 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 0.046 0.138 KET114 Eucalyptus Ketoprofen 10% 8 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 1.005 3.015 KET114 Eucalyptus Ketoprofen 10% 9 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 4.796 14.388 KET115 Eucalyptus Ketoprofen 10% 0 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 7.932 23.796 KET115 Eucalyptus ""d Ketoprofen 10% 1 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 118-cineole None 0.5 3 0.074 0.222 (") '"3 KET115 Eucalyptus s;;: Ketoprofen 10% 2 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 3 0.076 0.228 KET115 Eucalyptus ~ N Ketoprofen 10% 3 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 0.14 0.42 0 KET115 Eucalyptus ""' QC) Ketoprofen 10% 4 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 3 0.949 2.847 -0 KET115 Eucalyptus 0 Ketoprofen 10% 5 KET77 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 2.319 6.957 0 N KET115 Eucalyptus Ul Ketoprofen 10% 6 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 1 0.052 0.156 Ul KET115 Eucalyptus ~ Ketoprofen 10% 7 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 1 0.044 0.132 0 KET115 Eucalyptus N Ketoprofen 10% 8 KET78 KET115 Ethanol 50% EthOH lsomyristate 45% ISOMYR oEiul calyptus 3.5% 1,8-cineole None 4 1 0.DlS 0.045 -"10", 0' Ketoprofen 10% 9 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 1 0.378 1.134 ""' KET116 Eucalyptus w""' Ketoprofen 10% 0 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 1 1.624 4.872 0'I N KET116 Eucalyptus Ul Ketoprofen 10% 1 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 2 0.014 0.042 KET116 Eucalyptus Ketoprofen 10% 2 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 2 0.016 0.048 KET116 Eucalyptus Ketoprofen 10% 3 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 4 2 0.039 0.117 KET116 Eucalyptus Ketoprofen 10% 4 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 2 0.053 0.159 KET116 Eucalyptus Ketoprofen 10% 5 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 2 0.367 1.101 en KET116 Eucalyptus C Ketoprofen 10% 6 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 3 0.054 0.162 cr !!l. KET116 Eucalyptus e Ketoprofen 10% 7 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 3 0.015 0.045 ~ ro KET116 Eucalyptus 0 en Ketoprofen 10% 8 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 4 3 0.009 0.027 "0 ' :::, Eucalyptus "' (I) KET116 u, !2.

Ketoprofen 10% 9 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 3 0.799 2.397;:j """' ;a KET117 Eucalyptus "' "' C Ketoprofen 10% 0 KET78 Ethanol 50% EthOH lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 3 1.725 5.175 0 1D "' KET117 Eucalyptus 0 N I Ketoprofen 10% 1 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 1 0.012 0.036 0 ;0o) "' KET117 Eucalyptus ,.I . 0 Ketoprofen 10% 2 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 1 0.013 0.039 ,.. ► KET117 Eucalyptus C Ketoprofen 10% 3 KET79 Ethanol 50% EthOH Oley! alcohol 45%0A oil 3.5% 1,8-cineole None 4 1 0.038 0.114 KET117 Eucalyptus Ketoprofen 10% 4 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 1 0.194 0.582 KET117 Eucalyptus Ketoprofen 10% 5 KET79 Ethanol 50% EthOH Oley! alcohol 45%0A oil 3.5% 1,8-cineole None 8 1 0.534 1.602 KET117 Eucalyptus Ketoprofen 10% 6 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 2 0.045 0.135 KET117 Eucalyptus Ketoprofen 10% 7 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 2 0.049 0.147 KET117 Eucalyptus ""d Ketoprofen 10% 8 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 118-cineole None 4 2 0.074 0.222 (") '"3 KET117 Eucalyptus s;;: Ketoprofen 10% 9 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 2 0.197 0.591 KET118 Eucalyptus ~ N Ketoprofen 10% 0 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 8 2 0.387 1.161 0 KET118 Eucalyptus ""' QC) Ketoprofen 10% 1 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 3 0.09 0.27 -0 KET118 Eucalyptus 0 Ketoprofen 10% 2 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 3 0.049 0.147 0 N KET118 Eucalyptus Ul Ketoprofen 10% 3 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 4 3 0.048 0.144 Ul KET118 Eucalyptus ~ Ketoprofen 10% 4 KET79 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 3 0.055 0.165 0 KET118 Eucalyptus N Ketoprofen 10% 5 KET79 KET118 Ethanol 50% EthOH Oleyl alcohol 45%0A oEiul calyptus 3.5% 1,8-cineole None 8 3 0.17 0.51 -"10", 0' Ketoprofen 10% 6 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 1 0.059 0.177 ""' KET118 Eucalyptus w""' Ketoprofen 10% 7 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 1 0.066 0.198 0'I N KET118 Eucalyptus Ul Ketoprofen 10% 8 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 4 1 0.079 0.237 KET118 Eucalyptus Ketoprofen 10% 9 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 1 0.086 0.258 KET119 Eucalyptus Ketoprofen 10% 0 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 8 1 0.298 0.894 KET119 Eucalyptus Ketoprofen 10% 1 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 2 0.057 0.171 KET119 Eucalyptus Ketoprofen 10% 2 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 2 0.067 0.201 en KET119 Eucalyptus C Ketoprofen 10% 3 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 4 2 0.067 0.201 cr !!l. KET119 Eucalyptus e Ketoprofen 10% 4 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 2 0.079 0.237 ~ ro KET119 Eucalyptus 0 en Ketoprofen 10% 5 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 8 2 0.118 0.354 "0 ' :::, Eucalyptus "' (I) KET119 u, !2.

Ketoprofen 10% 6 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 0.5 3 0.07 0.21i """' ;a KET119 Eucalyptus "' "' C Ketoprofen 10% 7 KETSO lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 2 3 0.005 0.015 0 1D "' KET119 Eucalyptus 0 N I Ketoprofen 10% 8 KETSO lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 4 3 0.005 O.DlS 0 ;0o) "' KET119 Eucalyptus ,.I . 0 Ketoprofen 10% 9 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 6 3 0.006 O.Dl8 ,.. ► KET120 Eucalyptus C Ketoprofen 10% 0 KET80 lsopronanol 50% IPN Oleyl alcohol 45%0A oil 3.5% 1,8-cineole None 8 3 0.087 0.261 KET120 1-Ethyl-2- Flunixin 10% 1 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 1 0.005 O.Dl5 KET120 l-Ethyl-2- Flunixin 10% 2 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 2 1 0.006 O.Dl8 KET120 1-Ethyl-2- Flunixin 10% 3 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 4 1 0.008 0.024 KET120 1-Ethyl-2- Flunixin 10% 4 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 6 1 0.01 0.03 KET120 1-Ethyl-2- ""d Flunixin 10% s KET81 Ethanol 50% EthOH Pryrrolidone 4S%EP Menthol song/ml None 8 1 0.061 0.183 (") '"3 KET120 1-Ethyl-2- s;;: Flunixin 10% 6 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 0.5 2 0.051 0.153 KET120 1-Ethyl-2- ~ N Flunixin 10% 7 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 2 2 0.077 0.231 0 KET120 l-Ethyl-2- ""' QC) Flunixin 10% 8 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 4 2 0.081 0.243 -0 KET120 l-Ethyl-2- 0 Flunixin 10% 9 KET81 Ethanol 50% EthOH Pryrrolidone 4S%EP Menthol song/ml None 6 2 0.099 0.297 0 N KET121 l-Ethyl-2- Ul Flunixin 10% 0 KET81 Ethanol 50% EthOH Pryrrolidone 4S%EP Menthol song/ml None 8 2 0.111 0.333 Ul KET121 1-Ethyl-2- ~ Flunixin 10% 1 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 3 0 0 KET121 1-Ethyl-2- N Flunixin 10% K2E T121 KET81 Ethanol 50% EthOH 1P-rEyrthroylli-d2o-ne 45%EP Menthol song/ml None 2 3 0.005 0.015 -"10", 0' Flunixin 10% 3 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 4 3 0.008 0.024 ""' KET121 1-Ethyl-2- w""' Flunixin 10% 4 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 6 3 0.009 0.027 0'I N KET121 1-Ethyl-2- Ul Flunixin 10% 5 KET81 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 8 3 0.045 0.135 KET121 Eucalyptus Flunixin 10% 6 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0.005 0.015 KET121 Eucalyptus Flunixin 10% 7 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.006 0.018 KET121 Eucalyptus Flunixin 10% 8 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 1 0.006 0.018 KET121 Eucalyptus Flunixin 10% 9 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 1 0.009 0.027 en KET122 Eucalyptus C Flunixin 10% 0 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 1 0.024 0.072 cr !!l. KET122 Eucalyptus e Flunixin 10% 1 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 2 0.01 0.03 ~ ro KET122 Eucalyptus 0 en Flunixin 10% 2 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 0.01 0.03 "0 ' :::, Eucalyptus "' (I) KET122 u, !2.

Flunixin 10% 3 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 0.011 0.033;;! """' ;a KET122 Eucalyptus "' "' C Flunixin 10% 4 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 0.011 0.033 0 1D "' KET122 Eucalyptus 0 N I Flunixin 10% 5 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 0.024 0.072 0 ;0o) "' KET122 Eucalyptus I I-' 0 Flunixin 10% 6 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 3 ---- 0 I-' ► KET122 Eucalyptus C Flunixin 10% 7 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 3 ---- 0 KET122 Eucalyptus Flunixin 10% 8 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 0.007 0.021 KET122 Eucalyptus Flunixin 10% 9 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 3 0.006 0.018 KET123 Eucalyptus Flunixin 10% 0 KET82 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 0.007 0.021 KET123 1-Ethyl-2- Flunixin 10% 1 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 1 0.008 0.024 KET123 1-Ethyl-2- ""d Flunixin 10% 2 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 2 1 0.009 0.027 (") '"3 KET123 Hthyl-2- s;;: Flunixin 10% 3 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 4 1 0.008 0.024 KET123 1-Ethyl-2- ~ N Flunixin 10% 4 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 6 1 0.008 0.024 0 KET123 1-Ethyl-2· ""' QC) Flunixin 10% 5 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 8 1 0.351 1.053 -0 KET123 1-Ethyl-2· 0 Flunixin 10% 6 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 2 0.007 0.021 0 N KET123 Hthyl-2· Ul Flunixin 10% 7 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 2 2 0 Ul KET123 1-Ethyl-2- ~ Flunixin 10% 8 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 4 2 0 0 KET123 1-Ethyl-2- N Flunixin 10% 9K ET124 KET83 Ethanol 50% EthOH 1P-rEyrthroylli-d2o-ne 45%EP Menthol song/ml None 6 2 0.008 0.024 -"10", 0' Flunixin 10% 0 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol SOng/ml None 8 2 0.012 0.036 ""' KET124 1-Ethyl-2- w""' Flunixin 10% 1 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 0.5 3 0 0'I N KET124 1-Ethyl-2- Ul Flunixin 10% 2 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 2 3 0 KET124 1-Ethyl-2- Flunixin 10% 3 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 4 3 0.007 0.021 KET124 1-Ethyl-2- Flunixin 10% 4 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 6 3 0.006 0.018 KET124 1-Ethyl-2- Flunixin 10% 5 KET83 Ethanol 50% EthOH Pryrrolidone 45%EP Menthol song/ml None 8 3 0.035 0.105 KET124 Eucalyptus Flunixin 10% 6 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0.005 O.D15 en KET124 Eucalyptus C Flunixin 10% 7 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.006 O.D18 cr !!l. KET124 Eucalyptus e Flunixin 10% 8 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 1 0.006 O.D18 ~ ro KET124 Eucalyptus 0 en Flunixin 10% 9 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 1 0.006 0.018 "0 ' :::, Eucalyptus "' (I) KET125 .u.., !2.

Flunixin 10% 0 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 1 0.017 0.051 ~ ""'' ;a KET125 Eucalyptus "' C Flunixin 10% 1 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 2 9.98 29.94 0 1D "' KET125 Eucalyptus 0 N I Flunixin 10% 2 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 10.843 32.529 0 ;0o) "' KET125 Eucalyptus ,.I . 0 Flunixin 10% 3 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 12.381 37.143 ,.. ► KET125 Eucalyptus C Flunixin 10% 4 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 13.123 39.369 KET125 Eucalyptus Flunixin 10% 5 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 13.487 40.461 KET125 Eucalyptus Flunixin 10% 6 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 3 1.005 3.015 KET125 Eucalyptus Flunixin 10% 7 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 3 1.165 3.495 KET125 Eucalyptus Flunixin 10% 8 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 1.513 4.539 KET125 Eucalyptus ""d Flunixin 10% 9 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 118-cineole None 6 3 1.552 4.656 (") '"3 KET126 Eucalyptus s;;: Flunixin 10% 0 KET84 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 1.78 5.34 KET126 1-Ethyl-2- ~ N Ketoprofen 10% 1 KET85 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol 50ng/ml None 0.5 1 0.033 0.099 0 KET126 1-Ethyl-2· ""' QC) Ketoprofen 10% 2 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol 50ng/ml None 2 1 0.039 0.117 -0 KET126 1-Ethyl-2· 0 Ketoprofen 10% 3 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 4 1 0.047 0.141 0 N KET126 Hthyl-2· Ul Ketoprofen 10% 4 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 1 0.062 0.186 Ul KET126 1-Ethyl-2- ~ Ketoprofen 10% 5 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 1 0.068 0.204 0 KET126 1-Ethyl-2- N Ketoprofen 10% 6K ET126 KET85 lsopronanol 50% IPN 1P-rEyrthroylli-d2o-ne 45%EP Menthol song/ml None 0.5 2 0.019 0.057 -"10", 0' Ketoprofen 10% 7 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol 50ng/ml None 2 2 0.054 0.162 ""' KET126 1-Ethyl-2- w""' Ketoprofen 10% 8 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 4 2 0.059 0.177 0'I N KET126 1-Ethyl-2- Ul Ketoprofen 10% 9 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 2 0.058 0.174 KET127 1-Ethyl-2- Ketoprofen 10% 0 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 2 0.059 0.177 KET127 1-Ethyl-2- Ketoprofen 10% 1 KET85 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 0.5 3 0.008 0.024 KET127 1-Ethyl-2- Ketoprofen 10% 2 KET85 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 2 3 0.013 0.039 KET127 1-Ethyl-2- Ketoprofen 10% 3 KET8S lsopronanol SO% IPN Pryrrolidone 4S%EP Menthol song/ml None 4 3 0.024 0.072 en KET127 Hthyl-2- C Ketoprofen 10% 4 KET85 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 6 3 0.053 0.159 cr !!l. KET127 Hthyl-2- e Ketoprofen 10% s KET85 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 8 3 0.06 0.18 ~ ro KET127 0 en Ketoprofen 10% 6 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 0.5 1 0.061 0.183 "0 ' :::, "' (I) KET127 .u.., !2.

Ketoprofen 10% 7 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 2 1 0.142 0.426 ::j ""'' ;a KET127 "' C Ketoprofen 10% 8 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol SOng/ml None 4 1 0.283 0.849 0 1D "' KET127 0 N I Ketoprofen 10% 9 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 6 1 0.322 0.966 0 ;0o) "' KET128 ,.I . 0 Ketoprofen 10% 0 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 8 1 0.356 1.068 ,.. ► KET128 C Ketoprofen 10% 1 KET86 lsopronanol 50% IPN Propylene glycol 4S% PPG Menthol song/ml None 0.5 2 0.014 0.042 KET128 Ketoprofen 10% 2 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 2 2 0.017 0.051 KET128 Ketoprofen 10% 3 KET86 lsopronanol 50% IPN Propylene glycol 4S% PPG Menthol song/ml None 4 2 0.027 0.081 KET128 Ketoprofen 10% 4 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol song/ml None 6 2 0.049 0.147 KET128 Ketoprofen 10% 5 KET86 lsopronano! 50% IPN Propylene glycol 45% PPG Menthol song/ml None 8 2 0.043 0.129 KET128 ""d Ketoprofen 10% 6 KET86 lsopronano! 50% IPN Propylene glycol 45% PPG Menthol song/ml None 0.5 3 0.048 0.144 (") '"3 KET128 s;;: Ketoprofen 10% 7 KET86 lsopronano! 50% IPN Propylene glycol 45% PPG Menthol SOng/ml None 2 3 0.045 0.135 KET128 ~ N Ketoprofen 10% 8 KET86 lsopronano! 50% IPN Propylene glycol 45% PPG Menthol 50ng/ml None 4 3 0.045 0.135 0 KET128 ""' QC) Ketoprofen 10% 9 KET86 lsopronanol 50% IPN Propylene glycol 45% PPG Menthol SOng/ml None 6 3 0.053 0.159 -0 KET129 0 Ketoprofen 10% 0 KET86 lsopronanol 50% IPN Propylene glycol 4S% PPG Menthol song/ml None 8 3 0.057 0.171 0 N KET129 Ul Ketoprofen 10% 1 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 0.5 1 0.018 0.054 Ul KET129 ~ Ketoprofen 10% 2 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 2 1 0.028 0.084 0 KET129 N Ketoprofen 10% 3K ET129 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 4 1 0.071 0.213 -"10", 0' Ketoprofen 10% 4 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol SOng/ml None 6 1 0.073 0.219 """"'' KET129 w Ketoprofen 10% 5 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 8 1 0.081 0.243 0'I N KET129 Ul Ketoprofen 10% 6 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 0.5 2 0.045 0.135 KET129 Ketoprofen 10% 7 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 2 2 0.038 0.114 KET129 Ketoprofen 10% 8 KET87 lsopronanol SO% IPN lsomyristate 45% ISOMYR Menthol song/ml None 4 2 0.072 0.216 KET129 Ketoprofen 10% 9 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 6 2 0.455 1.365 KET130 Ketoprofen 10% 0 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 8 2 0.476 1.428 en KET130 C Ketoprofen 10% 1 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 0.5 3 0.009 0.027 cr !!l. KET130 e Ketoprofen 10% 2 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 2 3 0.03 0.09 ~ ro KET130 0 en Ketoprofen 10% 3 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 4 3 0.03 0.09 "0 ' :::, "' (I) KET130 .u.., !2.

Ketoprofen 10% 4 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol song/ml None 6 3 0.129 0.387~ ""'' ;a KET130 "' C Ketoprofen 10% 5 KET87 lsopronanol 50% IPN lsomyristate 45% ISOMYR Menthol SOng/ml None 8 3 0.233 0.699 0 1D "' KET130 0.1M 0 N I Ketoprofen 10% 6 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 0.5 1 0.01 0.03 0 ;0o) "' KET130 0.1M ,.I . 0 Ketoprofen 10% 7 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 2 1 0.013 0.039 ,.. ► KET130 0.1M C Ketoprofen 10% 8 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 4 1 0.012 0.036 KET130 0.1M Ketoprofen 10% 9 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 6 1 0.018 0.054 KET131 O.lM Ketoprofen 10% 0 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 8 1 0.026 0.078 KET131 0.1M Ketoprofen 10% 1 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 0.5 2 0.007 0.021 KET131 0.1M Ketoprofen 10% 2 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 2 2 0.009 0.027 KET131 0.1M ""d Ketoprofen 10% 3 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 4 2 0.034 0.102 (") '"3 KET131 0.1M s;;: Ketoprofen 10% 4 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol SOng/ml citrate 6 2 0.047 0.141 KET131 0.1M ~ N Ketoprofen 10% 5 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol SOng/ml citrate 8 2 0.315 0.945 0 KET131 0.1M ""' QC) Ketoprofen 10% 6 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol SOng/ml citrate 0.5 3 0.049 0.147 -0 KET131 0.1M 0 Ketoprofen 10% 7 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 2 3 0.045 0.135 0 N KET131 0.1M Ul Ketoprofen 10% 8 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 4 3 0.047 0.141 Ul KET131 O.lM ~ Ketoprofen 10% 9 KET88 Ethanol 50% EthOH Oley! alcohol 45%0A Menthol song/ml citrate 6 3 0.047 0.141 0 KET132 O.lM N Ketoprofen 10% 0 KET88 KET132 Ethanol 50% EthOH O1-lEeyth! yall-c2o-hol 45%0A EMuecnatlhypotlu s song/ml citrate 8 3 0.03 0.09 -"10", 0' Ketoprofen 10% 1 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 0.5 1 0.008 0.024 ""' KET132 1-Ethyl-2- Eucalyptus w""' Ketoprofen 10% 2 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 1 0.009 0.027 0'I N KET132 1-Ethyl-2- Eucalyptus Ul Ketoprofen 10% 3 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 1 0.013 0.039 KET132 1-Ethyl-2- Eucalyptus Ketoprofen 10% 4 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 1 0.009 0.027 KET132 1-Ethyl-2- Eucalyptus Ketoprofen 10% 5 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 1 0.038 0.114 KET132 1-Ethyl-2- Eucalyptus Ketoprofen 10% 6 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 0.5 2 0.027 0.081 KET132 1-Ethyl-2- Eucalyptus Ketoprofen 10% 7 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 2 0.029 0.087 en KET132 1-Ethyl-2- Eucalyptus C Ketoprofen 10% 8 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 2 0.023 0.069 cr !!l. KET132 1-Ethyl-2- Eucalyptus e Ketoprofen 10% 9 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 2 0.033 0.099 ~ ro KET133 1-Ethyl-2- Eucalyptus 0 en Ketoprofen 10% 0 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 2 0.035 0.105 "0 ' :::, 1-Ethyl-2- Eucalyptus "' (I) KET133 .u.., !2.

Ketoprofen 10% 1 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 0.5 3 0.023 0.069i:3 ""'' ;a KET133 1-Ethyl-2- Eucalyptus "' C Ketoprofen 10% 2 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 2 3 0.023 0.069 0 1D "' KET133 1-Ethyl-2- Eucalyptus 0 N I Ketoprofen 10% 3 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 4 3 0.03 0.09 0 ;0o) "' KET133 1-Ethyl-2- Eucalyptus ,.I . 0 Ketoprofen 10% 4 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 6 3 0.036 0.108 ,.. ► KET133 1-Ethyl-2- Eucalyptus C Ketoprofen 10% 5 KET89 lsopronanol 50% IPN Pryrrolidone 45%EP oil 3.5% 1,8-cineole None 8 3 0.113 0.339 KET133 Eucalyptus Ketoprofen 10% 6 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0.01 0.03 KET133 Eucalyptus Ketoprofen 10% 7 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.007 0.021 KET133 Eucalyptus Ketoprofen 10% 8 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 1 0.003 0.009 KET133 Eucalyptus Ketoprofen 10% 9 KET90 lsopronano! 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 1 0.009 0.027 KET134 Eucalyptus ""d Ketoprofen 10% 0 KET90 lsopronano! 50% IPN Propylene glycol 45% PPG oil 3.5% 118-cineole None 8 1 0.007 0.021 (") '"3 KET134 Eucalyptus s;;: Ketoprofen 10% 1 KET90 lsopronano! 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 2 0.007 0.021 KET134 Eucalyptus ~ N Ketoprofen 10% 2 KET90 lsopronano! 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 0.029 0.087 0 KET134 Eucalyptus ""' QC) Ketoprofen 10% 3 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 0.008 0.024 -0 KET134 Eucalyptus 0 Ketoprofen 10% 4 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 0.031 0.093 0 N KET134 Eucalyptus Ul Ketoprofen 10% 5 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 0.047 0.141 Ul KET134 Eucalyptus ~ Ketoprofen 10% 6 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 3 0.037 0.111 0 KET134 Eucalyptus N Ketoprofen 10% 7 KET90 lsopronanol KET134 50% IPN Propylene glycol 45% PPG oEiul calyptus 3.5% 1,8-cineole None 2 3 0.033 0.099 -"10", 0' Ketoprofen 10% 8 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 0.032 0.096 ""' KET134 Eucalyptus w""' Ketoprofen 10% 9 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 3 0.011 0.033 0'I N KET135 Eucalyptus Ul Ketoprofen 10% 0 KET90 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 0.006 0.018 KET135 Eucalyptus Ketoprofen 10% 1 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 1 0.011 0.033 KET135 Eucalyptus Ketoprofen 10% 2 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 1 0.007 0.021 KET135 Eucalyptus Ketoprofen 10% 3 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 4 1 0.008 0.024 KET135 Eucalyptus Ketoprofen 10% 4 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 1 0.024 0.072 en KET135 Eucalyptus C Ketoprofen 10% 5 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 1 0.069 0.207 cr !!l. KET135 Eucalyptus e Ketoprofen 10% 6 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 2 0.032 0.096 ~ ro KET135 Eucalyptus 0 en Ketoprofen 10% 7 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 2 0.026 0.078 "0 ' :::, Eucalyptus "' (I) KET135 u, !2.

Ketoprofen 10% 8 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 4 2 0.023 0.069~ """' ;a KET135 Eucalyptus "' "' C Ketoprofen 10% 9 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 2 0.007 0.021 0 1D "' KET136 Eucalyptus 0 N I Ketoprofen 10% 0 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 2 0.009 0.027 0 ;0o) "' KET136 Eucalyptus ,.I . 0 Ketoprofen 10% 1 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 0.5 3 0.006 0.018 ,.. ► KET136 Eucalyptus C Ketoprofen 10% 2 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 2 3 0.027 0.081 KET136 Eucalyptus Ketoprofen 10% 3 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 4 3 0.008 0.024 KET136 Eucalyptus Ketoprofen 10% 4 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 6 3 0.02 0.06 KET136 Eucalyptus Ketoprofen 10% 5 KET91 lsopronanol 50% IPN lsomyristate 45% ISOMYR oil 3.5% 1,8-cineole None 8 3 0.009 0.027 KET136 Eucalyptus O.lM Ketoprofen 10% 6 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 0.5 1 0.042 0.126 KET136 Eucalyptus 0.1M ""d Ketoprofen 10% 7 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 118-cineole citrate 2 1 0.042 0.126 (") '"3 KET136 Eucalyptus O.lM s;;: Ketoprofen 10% 8 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 4 1 0.016 0.048 KET136 Eucalyptus 0.1M ~ N Ketoprofen 10% 9 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 6 1 0.007 0.021 0 KET137 Eucalyptus O.lM ""' QC) Ketoprofen 10% 0 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 8 1 0.098 0.294 -0 KET137 Eucalyptus O.lM 0 Ketoprofen 10% 1 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 0.5 2 0.049 0.147 0 N KET137 Eucalyptus O.lM Ul Ketoprofen 10% 2 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 2 2 0.008 0.024 Ul KET137 Eucalyptus O.lM ~ Ketoprofen 10% 3 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 4 2 0.041 0.123 0 KET137 Eucalyptus O.lM N Ketoprofen 10% 4 KET92 Ethanol KET137 50% EthOH Oleyl alcohol 45%0A oEiul calyptus 3.5% 1,8-cineole Ocit.rlMat e 6 2 0.053 0.159 -"10", 0' Ketoprofen 10% 5 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 8 2 0.014 0.042 ""' KET137 Eucalyptus O.lM w""' Ketoprofen 10% 6 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 0.5 3 0.011 0.033 0'I N KET137 Eucalyptus O.lM Ul Ketoprofen 10% 7 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 2 3 0.046 0.138 KET137 Eucalyptus O.lM Ketoprofen 10% 8 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 4 3 0.039 0.117 KET137 Eucalyptus O.lM Ketoprofen 10% 9 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 6 3 0.023 0.069 KET138 Eucalyptus O.lM Ketoprofen 10% 0 KET92 Ethanol 50% EthOH Oleyl alcohol 45%0A oil 3.5% 1,8-cineole citrate 8 3 0.016 0.048 KET138 1-Ethyl-2- Flunixin 10% 1 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol 50ng/ml None 0.5 1 0.348 1.044 en KET138 1-Ethyl-2- C Flunixin 10% 2 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol 50ng/ml None 2 1 0.363 1.089 CY !!l. KET138 1-Ethyl-2- e Flunixin 10% 3 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol SOng/ml None 4 1 0.369 1.107 ~ ro KET138 1-Ethyl-2- 0 en Flunixin 10% 4 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 1 0.395 1.185 "0 ' :;:,- 1-Ethyl-2- "' (I) KET138 ,u.., !2.

Flunixin 10% 5 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 1 0.458 1.374 "Q"C'I ""'' ;a KET138 1-Ethyl-2- "' C Flunixin 10% 6 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol SOng/ml None 0.5 2 0.008 0.024 0 1D "' KET138 1-Ethyl-2- 0 N I Flunixin 10% 7 KET93 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 2 2 0.022 0.066 0 ;0o) "' KET138 1-Ethyl-2- ,_I . 0 Flunixin 10% 8 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol SOng/ml None 4 2 0.051 0.153 ,_. ► KET138 1-Ethyl-2- C Flunixin 10% 9 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol SOng/ml None 6 2 0.057 0.171 KET139 1-Ethyl-2- Flunixin 10% 0 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 8 2 0.089 0.267 KET139 1-Ethyl-2- Flunixin 10% 1 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 0.5 3 0.032 0.096 KET139 1-Ethyl-2- Flunixin 10% 2 KET93 lsopronanol 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 2 3 0.034 0.102 KET139 1-Ethyl-2- Flunixin 10% 3 KET93 lsopronano! 50% IPN Pryrrolidone 4S%EP Menthol song/ml None 4 3 0.181 0.543 KET139 1-Ethyl-2- ""d Flunixin 10% 4 KET93 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 3 0.193 0.579 (") '"3 KET139 1-Ethyl-2- s;;: Flunixin 10% 5 KET93 lsopronano! 50% IPN Pryrrolidone 4S%EP Menthol SOng/ml None 8 3 0.201 0.603 KET139 Eucalyptus ~ N Flunixin 10% 6 KET94 lsopronano! 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0.009 0.027 0 KET139 Eucalyptus "Q"C'I Flunixin 10% 7 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.045 0.135 -0 KET139 Eucalyptus 0 Flunixin 10% 8 KET94 lsopronanol 50% IPN Propylene glycol 4S% PPG oil 3.5% 1,8-cineole None 4 1 0.048 0.144 0 N KET139 Eucalyptus Ul Flunixin 10% 9 KET94 lsopronanol 50% IPN Propylene glycol 4S% PPG oil 3.5% 1,8-cineole None 6 1 0.051 0.153 Ul KET140 Eucalyptus ~ Flunixin 10% 0 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 1 0.056 0.168 0 KET140 Eucalyptus N Flunixin 10% 1 KET94 lsopronanol KET140 50% IPN Propylene glycol 45% PPG oEiul calyptus 3.5% 1,8-cineole None 0.5 2 0.036 0.108 -"10", 0' Flunixin 10% 2 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 0.041 0.123 ""' KET140 Eucalyptus w""' Flunixin 10% 3 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 0.042 0.126 0'I N KET140 Eucalyptus Ul Flunixin 10% 4 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 0.042 0.126 KET140 Eucalyptus Flunixin 10% 5 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 0.076 0.228 KET140 Eucalyptus Flunixin 10% 6 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 3 0.035 0.105 KET140 Eucalyptus Flunixin 10% 7 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 3 0.045 0.135 KET140 Eucalyptus Flunixin 10% 8 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 0.051 0.153 en KET140 Eucalyptus C Flunixin 10% 9 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 3 0.052 0.156 cr !!l. KET141 Eucalyptus e Flunixin 10% 0 KET94 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 0.068 0.204 ~ ro KET141 1-Ethyl-2- 0 en Flunixin 10% 1 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 0.5 1 0.053 0.159 "0 ' :::, l-Ethyl-2- "' (I) KET141 u, !2.

Flunixin 10% 2 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 2 1 0.055 0.165~ """' ;a KET141 l-Ethyl-2- "' "' C Flunixin 10% 3 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol SOng/ml None 4 1 0.062 0.186 0 1D "' KET141 l-Ethyl-2- 0 N I Flunixin 10% 4 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 1 0.062 0.186 0 ;0o) "' KET141 l-Ethyl-2- ,.I . 0 Flunixin 10% 5 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 1 0.066 0.198 ,.. ► KET141 l-Ethyl-2- C Flunixin 10% 6 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 0.5 2 0.079 0.237 KET141 1-Ethyl-2- Flunixin 10% 7 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 2 2 0.082 0.246 KET141 l-Ethyl-2- Flunixin 10% 8 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 4 2 0.095 0.285 KET141 1-Ethyl-2- Flunixin 10% 9 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 6 2 0.136 0.408 KET142 1-Ethyl-2- Flunixin 10% 0 KET95 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 2 0.165 0.495 KET142 1-Ethyl-2- ""d Flunixin 10% 1 KET95 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol song/ml None 0.2 3 0.038 0.114 (") '"3 KET142 1-Ethyl-2- s;;: Flunixin 10% 2 KET95 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol SOng/ml None 2 3 0.044 0.132 KET142 1-Ethyl-2- ~ N Flunixin 10% 3 KET95 lsopronano! 50% IPN Pryrrolidone 45%EP Menthol SOng/ml None 4 3 0.049 0.147 0 KET142 l-Ethyl-2- ""' QC) Flunixin 10% 4 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol SOng/ml None 6 3 0.064 0.192 -0 KET142 l-Ethyl-2- 0 Flunixin 10% 5 KET95 lsopronanol 50% IPN Pryrrolidone 45%EP Menthol song/ml None 8 3 0.155 0.465 0 N KET142 Eucalyptus Ul Flunixin 10% 6 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 1 0 Ul KET142 Eucalyptus ~ Flunixin 10% 7 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 1 0.007 0.021 0 KET142 Eucalyptus N Flunixin 10% 8 KET96 lsopronanol KET142 50% IPN Propylene glycol 45% PPG oEiul calyptus 3.5% 1,8-cineole None 4 1 0.031 0.093 -"10", 0' Flunixin 10% 9 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 1 0.032 0.096 ""' KET143 Eucalyptus w""' Flunixin 10% 0 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 1 0.02 0.06 0'I N KET143 Eucalyptus Ul Flunixin 10% 1 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 2 0.005 0.015 KET143 Eucalyptus Flunixin 10% 2 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 2 0.037 0.111 KET143 Eucalyptus Flunixin 10% 3 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 2 0.044 0.132 KET143 Eucalyptus Flunixin 10% 4 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 2 0.05 0.15 KET143 Eucalyptus Flunixin 10% 5 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 2 0.056 0.168 en KET143 Eucalyptus C Flunixin 10% 6 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 0.5 3 0.01 0.03 cr !!l. KET143 Eucalyptus e Flunixin 10% 7 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 2 3 0.011 0.033 ~ ro KET143 Eucalyptus 0 en Flunixin 10% 8 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 4 3 0.025 0.075 "0 ' :::, Eucalyptus "' (I) KET143 u, !2.

Flunixin 10% 9 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 6 3 0.025 0.075~ """' ;a KET144 Eucalyptus "' "' C Flunixin 10% 0 KET96 lsopronanol 50% IPN Propylene glycol 45% PPG oil 3.5% 1,8-cineole None 8 3 0.033 0.099 0 1D "' KET144 1-ethyl-2- Eucalyptus 0 N I Ketoprofen 10% 1 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 0.5 1 0.006 0.018 0 ;0o) "' KET144 1-ethyl-2- Eucalyptus ,.I . 0 Ketoprofen 10% 2 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 2 1 0.017 0.051 ,.. ► KET144 1-ethyl-2- Eucalyptus C Ketoprofen 10% 3 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 4 1 0.197 0.591 KET144 1-ethyl-2- Eucalyptus Ketoprofen 10% 4 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 6 1 0.76 2.28 KET144 1-ethyl-2- Eucalyptus Ketoprofen 10% 5 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 8 1 2.17 6.51 KET144 1-ethyl-2- Eucalyptus Ketoprofen 10% 6 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 0.5 2 0.011 0.033 KET144 1-ethyl-2- Eucalyptus Ketoprofen 10% 7 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 2 2 0.053 0.159 KET144 1-ethyl-2- Eucalyptus ""d Ketoprofen 10% 8 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 118-cineole NA 4 2 0.08 0.24 (") '"3 KET144 1-ethyl-2- Eucalyptus s;;: Ketoprofen 10% 9 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 6 2 0.532 1.596 KET145 1-ethyl-2- Eucalyptus ~ N Ketoprofen 10% 0 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 8 2 1.778 5.334 0 KET145 1-ethyl-2- Eucalyptus ""' QC) Ketoprofen 10% 1 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 0.5 3 0.014 0.042 -0 KET145 1-ethyl-2- Eucalyptus 0 Ketoprofen 10% 2 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 2 3 0.008 0.024 0 N KET145 1-ethyl-2- Eucalyptus Ul Ketoprofen 10% 3 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 4 3 0.119 0.357 Ul KET145 1-ethyl-2- Eucalyptus ~ Ketoprofen 10% 4 KET97 Ethanol 50% EthOH Pyrrolidinone 45% oil 3.5% 1,8-cineole NA 6 3 1.089 3.267 0 KET145 1-ethyl-2- Eucalyptus N Ketoprofen 10% 5 KET145 KET97 Ethanol 50% EthOH 1P-yertrhoylidl-i2n-one 45% oil 3.5% 1,8-cineole NA 8 3 3.325 9.975 -"10", 0' Ketoprofen 10% 6 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 0.5 1 0.006 0.018 ""' KET145 1-ethyl-2- w""' Ketoprofen 10% 7 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 2 1 0.026 0.078 0'I N KET145 1-ethyl-2- Ul Ketoprofen 10% 8 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 118-cineole NA 4 1 0.063 0.189 KET145 1-ethyl-2- Ketoprofen 10% 9 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 6 1 0.187 0.561 KET146 1-ethyl-2- Ketoprofen 10% 0 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 118-cineole NA 8 1 2.145 6.435 KET146 1-ethyl-2- Ketoprofen 10% 1 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 0.5 2 0.016 0.048 KET146 1-ethyl-2- Ketoprofen 10% 2 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 2 2 0.011 0.033 en KET146 1-ethyl-2- C Ketoprofen 10% 3 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 4 2 0.735 2.205 cr !!l. KET146 1-ethyl-2- e Ketoprofen 10% 4 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 6 2 3.096 9.288 ~ ro KET146 1-ethyl-2- 0 en Ketoprofen 10% 5 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 8 2 13.125 39.375 "0 ' :::, 1-ethyl-2- "' (I) KET146 .u.., !2.

Ketoprofen 10% 6 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 118-cineole NA 0.5 3 0.007 0.021~ ""'' ;a KET146 1-ethyl-2- "' C Ketoprofen 10% 7 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 118-cineole NA 2 3 0.031 0.093 0 1D "' KET146 1-ethyl-2- 0 N I Ketoprofen 10% 8 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 118-cineole NA 4 3 0.058 0.174 0 ;0o) "' KET146 1-ethyl-2- ,.I . 0 Ketoprofen 10% 9 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 6 3 0.615 1.845 ,.. ► KET147 1-ethyl-2- C Ketoprofen 10% 0 KET98 Ethanol 50% EthOH Pyrrolidinone 45% Eucalyptol 5% 1,8-cineole NA 8 3 0.946 2.838 KET147 1-ethyl-2- Ketoprofen 10% 1 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 0.5 1 O.D7 0.21 KET147 1-ethyl-2- Ketoprofen 10% 2 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 2 1 O.Q18 0.054 KET147 1-ethyl-2- Ketoprofen 10% 3 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 4 1 0.027 0.081 KET147 1-ethyl-2- Ketoprofen 10% 4 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 6 1 0.216 0.648 KET147 1-ethyl-2- ""d Ketoprofen 10% 5 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 8 1 2.211 6.633 (") '"3 KET147 1-ethyl-2- s;;: Ketoprofen 10% 6 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 0.5 2 0.007 0.021 KET147 1-ethyl-2- ~ N Ketoprofen 10% 7 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 2 2 O.Ql 0.03 0 KET147 1-ethyl-2· ""' QC) Ketoprofen 10% 8 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 4 2 0.044 0.132 -0 KET147 1-ethyl-2· 0 Ketoprofen 10% 9 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 6 2 0.571 1.713 0 N KET148 1-ethyl-2· Ul Ketoprofen 10% 0 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 8 2 2.014 6.042 Ul KET148 1-ethyl-2- ~ Ketoprofen 10% 1 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 0.2 3 0.016 0.048 0 KET148 1-ethyl-2- N Ketoprofen 10% 2 KET148 KET99 Ethanol 45% EthOH 1P-yertrhoylidl-i2n-one 45% Eucalyptol 10% 1,8-cineole NA 2 3 0.017 0.051 -"10", 0' Ketoprofen 10% 3 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 4 3 0.041 0.123 ""' KET148 1-ethyl-2- w""' Ketoprofen 10% 4 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 6 3 0.658 1.974 0'I N KET148 1-ethyl-2- Ul Ketoprofen 10% 5 KET99 Ethanol 45% EthOH Pyrrolidinone 45% Eucalyptol 10% 1,8-cineole NA 8 3 2.793 8.379 KET148 Eucalyptus Ketoprofen 10% 6 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 0.5 1 0.007 0.021 KET148 Eucalyptus Ketoprofen 10% 7 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 2 1 0.036 0.108 KET148 Eucalyptus Ketoprofen 10% 8 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 4 1 1.648 4.944 KET148 Eucalyptus Ketoprofen 10% 9 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 6 1 5.855 17.565 en KET149 Eucalyptus C Ketoprofen 10% 0 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 1 8.245 24.735 cr !!l. KET149 Eucalyptus e Ketoprofen 10% 1 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 0.5 2 0.008 0.024 ~ ro KET149 Eucalyptus 0 en Ketoprofen 10% 2 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 2 2 0.058 0.174 "0 ' :::, Eucalyptus "' (I) KET149 .u.., !2.

Ketoprofen 10% 3 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 4 2 0.061 0.183~ ""'' ;a KET149 Eucalyptus "' C Ketoprofen 10% 4 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 6 2 0.386 1.158 0 1D "' KET149 Eucalyptus 0 N I Ketoprofen 10% 5 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 8 2 1.636 4.908 0 ;0o) "' KET149 Eucalyptus ,.I . 0 Ketoprofen 10% 6 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 0.5 3 0.007 0.021 ,.. ► KET149 Eucalyptus C Ketoprofen 10% 7 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 2 3 0.01 0.03 KET149 Eucalyptus Ketoprofen 10% 8 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 4 3 0.528 1.584 KET149 Eucalyptus Ketoprofen 10% 9 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 6 3 1.779 5.337 KET150 Eucalyptus Ketoprofen 10% 0 KETlOO Ethanol 50% EthOH Propylene glycol 45% oil 3.5% 1,8-cineole NA 8 3 3.593 10.779 KETlSO Ketoprofen 10% 1 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 0.5 1 0.009 0.027 KETlSO ""d Ketoprofen 10% 2 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 118-cineole NA 2 1 0.011 0.033 (") '"3 KET150 s;;: Ketoprofen 10% 3 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 4 1 0.024 0.072 KET150 ~ N Ketoprofen 10% 4 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 118-cineole NA 6 1 0.073 0.219 0 KET150 ""' QC) Ketoprofen 10% 5 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 8 1 0.076 0.228 -0 KETlSO 0 Ketoprofen 10% 6 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 0.5 2 0.016 0.048 0 N KET150 Ul Ketoprofen 10% 7 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 2 2 0.015 0.045 Ul KET150 ~ Ketoprofen 10% 8 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 4 2 0.071 0.213 0 KET150 N Ketoprofen 10% 9 KET151 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 6 2 0.406 1.218 -"10", 0' Ketoprofen 10% 0 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 8 2 0.927 2.781 """"'' KET151 w Ketoprofen 10% 1 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 0.5 3 0.008 0.024 0'I N KET151 Ul Ketoprofen 10% 2 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 118-cineole NA 2 3 0.009 0.027 KET151 Ketoprofen 10% 3 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 4 3 0.012 0.036 KET151 Ketoprofen 10% 4 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 118-cineole NA 6 3 0.022 0.066 KET151 Ketoprofen 10% 5 KET101 Ethanol 50% EthOH Propylene glycol 45% Eucalyptol 5% 1,8-cineole NA 8 3 0.067 0.201 KET151 Ketoprofen 10% 6 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 0.5 1 0.02 0.06 en KET151 C Ketoprofen 10% 7 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 2 1 0.009 0.027 cr !!l. KET151 e Ketoprofen 10% 8 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 4 1 0.01 0.03 ~ ro KET151 0 en Ketoprofen 10% 9 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 6 1 0.035 0.105 "0 ' :;:,- "' (I) KET152 .u.., !2.

Ketoprofen 10% 0 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 8 1 0.232 0.696~ ""'' ;a KET152 "' C Ketoprofen 10% 1 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 0.5 2 0.017 0.051 0 1D "' KET152 0 N I Ketoprofen 10% 2 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 2 2 0.01 0.03 0 ;0o) "' KET152 I I-' 0 Ketoprofen 10% 3 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 4 2 1.039 3.117 I-' ► KET152 C Ketoprofen 10% 4 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 6 2 3.834 11.502 KET152 Ketoprofen 10% 5 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 8 2 5.482 16.446 KET152 Ketoprofen 10% 6 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 0.5 3 0.012 0.036 KET152 Ketoprofen 10% 7 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 2 3 0.007 0.021 KET152 Ketoprofen 10% 8 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 4 3 0.073 0.219 KET152 ""d Ketoprofen 10% 9 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 6 3 0.387 1.161 (") '"3 KET153 s;;: Ketoprofen 10% 0 KET102 Ethanol 45% EthOH Propylene glycol 45% Eucalyptol 10% 1,8-cineole NA 8 3 2.96 8.88 KET153 lsopropyl Eucalyptus ~ N Ketoprofen 10% 1 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 0.5 1 0.006 O.Q18 0 KET153 lsopropyl Eucalyptus ""' QC) Ketoprofen 10% 2 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 2 1 0.024 0.072 -0 KET153 lsopropyl Eucalyptus 0 Ketoprofen 10% 3 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 4 1 0.056 0.168 0 N KET153 lsopropyl Eucalyptus Ul Ketoprofen 10% 4 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 6 1 1.446 4.338 Ul KET153 lsopropyl Eucalyptus ~ Ketoprofen 10% 5 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 8 1 7.744 23.232 0 KET153 lsopropyl Eucalyptus N Ketoprofen 10% 6 KET103 KET153 Ethanol 50% EthOH lmsoyprirsotaptyel 45% oEiul calyptus 3.5% 1,8-cineole NA 0.5 2 0.016 0.048 -"10", 0' Ketoprofen 10% 7 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 2 2 0.027 0.081 ""' KET153 lsopropyl Eucalyptus w""' Ketoprofen 10% 8 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 4 2 0.098 0.294 0'I N KET153 lsopropyl Eucalyptus Ul Ketoprofen 10% 9 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 6 2 1.245 3.735 KET154 lsopropyl Eucalyptus Ketoprofen 10% 0 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 8 2 4.178 12.534 KET154 lsopropyl Eucalyptus Ketoprofen 10% 1 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 0.2 3 0.012 0.036 KET154 lsopropyl Eucalyptus Ketoprofen 10% 2 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 2 3 0.013 0.039 KET154 lsopropyl Eucalyptus Ketoprofen 10% 3 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 4 3 0.371 1.113 en KET154 lsopropyl Eucalyptus C Ketoprofen 10% 4 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 6 3 1.317 3.951 cr !!l. KET154 lsopropyl Eucalyptus e Ketoprofen 10% 5 KET103 Ethanol 50% EthOH myristate 45% oil 3.5% 1,8-cineole NA 8 3 2.867 8.601 ~ ro KET154 lsopropyl 0 en Ketoprofen 10% 6 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 0.5 1 0.009 0.027 "0 ' :::, lsopropyl "' (I) KET154 u, !2.

Ketoprofen 10% 7 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 2 1 0.008 0.024~ """' ;a KET154 lsopropyl "' "' C Ketoprofen 10% 8 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 4 1 0.013 0.039 0 1D "' KET154 lsopropyl 0 N I Ketoprofen 10% 9 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 6 1 0.083 0.249 0 ;0o) "' KET155 lsopropyl ,.I . 0 Ketoprofen 10% 0 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 1 0.759 2.277 ,.. ► KET155 lsopropyl C Ketoprofen 10% 1 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 0.5 2 0.013 0.039 KET155 lsopropyl Ketoprofen 10% 2 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 2 2 0.014 0.042 KET155 lsopropyl Ketoprofen 10% 3 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 4 2 0.031 0.093 KET155 lsopropyl Ketoprofen 10% 4 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 6 2 0.573 1.719 KET155 lsopropyl Ketoprofen 10% 5 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 8 2 2.519 7.557 KET155 lsopropyl ""d Ketoprofen 10% 6 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 0.5 3 0.012 0.036 (") '"3 KET155 lsopropyl s;;: Ketoprofen 10% 7 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 2 3 0.023 0.069 KET155 lsopropyl ~ N Ketoprofen 10% 8 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 118-cineole NA 4 3 0.077 0.231 0 KET155 lsopropyl ""' QC) Ketoprofen 10% 9 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 6 3 0.097 0.291 -0 KET156 lsopropyl 0 Ketoprofen 10% 0 KET104 Ethanol 50% EthOH myristate 45% Eucalyptol 5% 1,8-cineole NA 8 3 0.442 1.326 0 N KET156 lsopropyl Ul Ketoprofen 10% 1 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 0.5 1 0.012 0.036 Ul KET156 lsopropyl ~ Ketoprofen 10% 2 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 2 1 0.012 0.036 0 KET156 lsopropyl N Ketoprofen 10% 3 KET156 KET105 Ethanol 45% EthOH lmsoyprirsotaptyel 45% Eucalyptol 10% 1,8-cineole NA 4 1 0.096 0.288 -"10", 0' Ketoprofen 10% 4 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 6 1 1.331 3.993 ""' KET156 lsopropyl w""' Ketoprofen 10% 5 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 8 1 1.527 4.581 0'I N KET156 lsopropyl Ul Ketoprofen 10% 6 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 0.5 2 0.009 0.027 KET156 lsopropyl Ketoprofen 10% 7 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 2 2 0.017 0.051 KET156 lsopropyl Ketoprofen 10% 8 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 4 2 0.017 0.051 KET156 lsopropyl Ketoprofen 10% 9 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 6 2 0.084 0.252 KET157 lsopropyl Ketoprofen 10% 0 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 8 2 0.423 1.269 en KET157 lsopropyl C Ketoprofen 10% 1 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 0.5 3 0.008 0.024 cr !!l. KET157 lsopropyl e Ketoprofen 10% 2 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 2 3 0.013 0.039 ~ ro KET157 lsopropyl 0 en Ketoprofen 10% 3 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 4 3 0.015 0.045 "0 ' :;:,- lsopropyl "' (I) KET157 .u.., !2.

Ketoprofen 10% 4 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 6 3 0.12 0.36~ ""'' ;a KET157 lsopropyl "' C Ketoprofen 10% 5 KET105 Ethanol 45% EthOH myristate 45% Eucalyptol 10% 1,8-cineole NA 8 3 0.479 1.437 0 1D "' KET157 0 N I Ketoprofen 10% 6 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 0,5 1 0.014 0.042 0 ;0o) "' KET157 I I-' 0 Ketoprofen 10% 7 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 2 1 0.014 0.042 I-' ► KET157 C Ketoprofen 10% 8 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 4 1 0.086 0.258 KET157 Ketoprofen 10% 9 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 6 1 0.411 1.233 KET158 Ketoprofen 10% 0 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 8 1 1.24 3.72 KET158 Ketoprofen 10% 1 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol 50mg/ml NA 0.5 2 O.Ql8 0.054 KET158 Ketoprofen 10% 2 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/ml NA 2 2 0.024 0.072 KET158 ""d Ketoprofen 10% 3 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol SOmg/mL NA 4 2 0.04 0.12 (") '"3 KET158 s;;: Ketoprofen 10% 4 KET106 Ethanol 50% EthOH Oleyl alcohol 50% Menthol SOmg/ml NA 6 2 0.539 1.617 KET158 ~ N Ketoprofen 10% 5 KET106 Ethanol 50% EthOH Oleyl alcohol 50% Menthol SOmg/mL NA 8 2 1.232 3.696 0 KET158 ""' QC) Ketoprofen 10% 6 KET106 Ethanol 50% EthOH Oleyl alcohol 50% Menthol 50mg/ml NA 0.5 3 0.008 0.024 -0 KET158 0 Ketoprofen 10% 7 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol 50mg/ml NA 2 3 O.Q18 0.054 0 N KET158 Ul Ketoprofen 10% 8 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol 50mg/ml NA 4 3 0.066 0.198 Ul KET158 ~ Ketoprofen 10% 9 KET106 Ethanol 50% EthOH Oley! alcohol 50% Menthol 50mg/ml NA 6 3 0.285 0.855 0 KET159 N Ketoprofen 10% 0 KET159 KET106 Ethanol 50% EthOH Oley! alcohol 50% EMuecnatlhypotlu s 50mg/ml NA 8 3 0.706 2.118 -"10", 0' Ketoprofen 10% 1 KET107 Ethanol 50% EthOH Oley! alcohol 45% oil 3.5% 1,8-cineole NA 0.5 1 0.01 0.03 ""' KET159 Eucalyptus w""' Ketoprofen 10% 2 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 2 1 0.018 0.054 0'I N KET159 Eucalyptus Ul Ketoprofen 10% 3 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 4 1 0.015 0.045 KET159 Eucalyptus Ketoprofen 10% 4 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 6 1 0.027 0.081 KET159 Eucalyptus Ketoprofen 10% 5 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 8 1 2.993 8.979 KET159 Eucalyptus Ketoprofen 10% 6 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 0.5 2 0.006 0.018 KET159 Eucalyptus Ketoprofen 10% 7 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 2 2 0.011 0.033 en KET159 Eucalyptus C Ketoprofen 10% 8 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 4 2 0.014 0.042 cr !!l. KET159 Eucalyptus e Ketoprofen 10% 9 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 6 2 0.018 0.054 ~ ro KET160 Eucalyptus 0 en Ketoprofen 10% 0 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 8 2 11.722 35.166 "0 ' :::, Eucalyptus "' (I) KET160 ,u.., !2.

Ketoprofen 10% 1 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 0.2 3 0.009 0.027~ ""'' ;a KET160 Eucalyptus "' C Ketoprofen 10% 2 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 2 3 0.012 0.036 0 1D "' KET160 Eucalyptus 0 N I Ketoprofen 10% 3 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 4 3 0.014 0.042 0 ;0o) "' KET160 Eucalyptus ,.I . 0 Ketoprofen 10% 4 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 6 3 0.012 0.036 ,.. ► KET160 Eucalyptus C Ketoprofen 10% 5 KET107 Ethanol 50% EthOH Oleyl alcohol 45% oil 3.5% 1,8-cineole NA 8 3 1.94 5.82 KET160 Ketoprofen 10% 6 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 0.5 1 0.009 0.027 KET160 Ketoprofen 10% 7 KET108 Ethanol 50% EthOH Oley! alcohol 45% Eucalyptol 5% 1,8-cineole NA 2 1 0.008 0.024 KET160 Ketoprofen 10% 8 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 118-cineole NA 4 1 0.01 0.03 KET160 Ketoprofen 10% 9 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 6 1 0.02 0.06 KET161 ""d Ketoprofen 10% 0 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 118-cineole NA 1 3.517 10.551 (") '"3 KET161 s;;: Ketoprofen 10% 1 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 0.5 2 0.009 0.027 KET161 ~ N Ketoprofen 10% 2 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 118-cineole NA 2 2 0.011 0.033 0 KET161 ""' QC) Ketoprofen 10% 3 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 4 2 0.01 0.03 -0 KET161 0 Ketoprofen 10% 4 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 6 2 0.011 0.033 0 N KET161 Ul Ketoprofen 10% 5 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 8 2 0.475 1.425 Ul KET161 ~ Ketoprofen 10% 6 KET108 Ethanol 50% EthOH Oley! alcohol 45% Eucalyptol 5% 1,8-cineole NA 0.5 3 0.008 0.024 0 KET161 N Ketoprofen 10% 7 KET161 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 2 3 0.009 0.027 -"10", 0' Ketoprofen 10% 8 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 4 3 0.009 0.027 """"'' KET161 w Ketoprofen 10% 9 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 1,8-cineole NA 6 3 0.006 0.018 0'I N KET162 Ul Ketoprofen 10% 0 KET108 Ethanol 50% EthOH Oleyl alcohol 45% Eucalyptol 5% 118-cineole NA 8 3 0.988 2.964 KET162 Eucalyptus Flunixin 10% 1 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 0.5 1 0.032 0.096 KET162 Eucalyptus Flunixin 10% 2 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 2 1 0.03 0.09 KET162 Eucalyptus Flunixin 10% 3 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 4 1 0.044 0.132 KET162 Eucalyptus Flunixin 10% 4 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 6 1 0.156 0.468 en KET162 Eucalyptus C Flunixin 10% 5 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 8 1 2.307 6.921 cr !!l. KET162 Eucalyptus e Flunixin 10% 6 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 0.5 2 0.032 0.096 ~ ro KET162 Eucalyptus 0 en Flunixin 10% 7 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 2 2 0.029 0.087 "0 ' :;:,- Eucalyptus "' (I) KET162 .u.., !2.

Flunixin 10% 8 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 4 2 0.021 0.063~ ""'' ;a KET162 Eucalyptus "' C Flunixin 10% 9 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 6 2 0.09 0.27 0 1D "' KET163 Eucalyptus 0 N I Flunixin 10% 0 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 8 2 0.196 0.588 0 ;0o) "' KET163 Eucalyptus I I-' 0 Flunixin 10% 1 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 0.5 3 0.032 0.096 I-' ► KET163 Eucalyptus C Flunixin 10% 2 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 2 3 0.123 0.369 KET163 Eucalyptus Flunixin 10% 3 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 4 3 0.189 0.567 KET163 Eucalyptus Flunixin 10% 4 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 6 3 0.355 1.065 KET163 Eucalyptus Flunixin 10% 5 KET109 Ethanol 50% EthOH Propylene glycol 45% PPG oil 3.5% 1,8-cineole NA 8 3 0.933 2.799 KET163 Flunixin 10% 6 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 0.5 1 0.028 0.084 KET163 ""d Flunixin 10% 7 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 118-cineole NA 2 1 0.022 0.066 (") '"3 KET163 s;;: Flunixin 10% 8 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 4 1 0.02 0.06 KET163 ~ N Flunixin 10% 9 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 118-cineole NA 6 1 0.035 0.105 0 KET164 ""' QC) Flunixin 10% 0 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 8 1 0.035 0.105 -0 KET164 0 Flunixin 10% 1 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 0.5 2 0.019 0.057 0 N KET164 Ul Flunixin 10% 2 KETllO Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 2 2 0.019 0.057 Ul KET164 ~ Flunixin 10% 3 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 4 2 0.025 0.075 0 KET164 N Flunixin 10% 4 KET110 KET164 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 6 2 0.034 0.102 -"10", 0' Flunixin 10% 5 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 8 2 0.184 0.552 """"'' KET164 w Flunixin 10% 6 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 0.5 3 0.022 0.066 0'I N KET164 Ul Flunixin 10% 7 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 118-cineole NA 2 3 0.039 0.117 KET164 Flunixin 10% 8 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 4 3 0.037 0.111 KET164 Flunixin 10% 9 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 118-cineole NA 6 3 0.042 0.126 KET165 Flunixin 10% 0 KET110 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 5% 1,8-cineole NA 8 3 0.076 0.228 KET165 Flunixin 10% 1 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 0.5 1 0.42 1.26 en KET165 C Flunixin 10% 2 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 2 1 0.402 1.206 cr !!l. KET165 e Flunixin 10% 3 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 4 1 0.406 1.218 ~ ro KET165 0 en Flunixin 10% 4 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 6 1 0.806 2.418 "0 ' :;:,- "' (I) KET165 .u.., !2.

Flunixin 10% 5 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 8 1 1.345 4.035 "\0"' ""'' ;a KET165 "' C Flunixin 10% 6 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 0.5 2 0.038 0.114 0 1D "' KET165 0 N I Flunixin 10% 7 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 2 2 0.045 0.135 0 ;0o) "' KET165 ,.I . 0 Flunixin 10% 8 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 4 2 0.046 0.138 ,.. ► KET165 C Flunixin 10% 9 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 6 2 0.082 0.246 KET166 Flunixin 10% 0 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 8 2 0.141 0.423 KET166 Flunixin 10% 1 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 0.2 3 0.063 0.189 KET166 Flunixin 10% 2 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 2 3 0.044 0.132 KET166 Flunixin 10% 3 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 4 3 0.028 0.084 KET166 ""d Flunixin 10% 4 KETlll Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 6 3 0.041 0.123 (") '"3 KET166 s;;: Flunixin 10% 5 KET111 Ethanol 50% EthOH Propylene glycol 45% PPG Eucalyptol 10% 1,8-cineole NA 8 3 0.633 1.899 KET170 Propylene ~ N Ketoprofen 10% 1 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.04 0.12 0 KET170 Propylene "Q"C') Ketoprofen 10% 2 KETllZ Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.018 0.054 -0 KET170 Propylene 0 Ketoprofen 10% 3 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.264 0.792 N KET170 Propylene Ul Ul Ketoprofen 10% 4 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 1 1.666 4.998 KET170 Propylene ~ Ketoprofen 10% 5 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 1 8.688 26.064 0 KET170 Propylene N Ketoprofen 10% 6K ET170 KET112 Ethanol gPlryocpoyl lene 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.1 0.3 -"10", 0' Ketoprofen 10% 7 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.045 0.135 ""' KET170 Propylene w""' Ketoprofen 10% 8 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.048 0.144 0'I N KET170 Propylene Ul Ketoprofen 10% 9 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole No 6 2 0.084 0.252 KET171 Propylene Ketoprofen 10% 0 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.805 2.415 KET171 Propylene Ketoprofen 10% 1 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole No 0.5 3 0.059 0.177 KET171 Propylene Ketoprofen 10% 2 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.023 0.069 KET171 Propylene Ketoprofen 10% 3 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.041 0.123 en KET171 Propylene C Ketoprofen 10% 4 KET112 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.096 0.288 cr !!l. KET171 Propylene 3.5% 1,8- e Ketoprofen 10% 5 KET112 Ethanol glycol 30:70 Eucalyptus oil cineole No 8 3 0.323 0.969 ~ ro KET171 Propylene 0 l.,J en Ketoprofen 10% 6 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 0.5 1 0.094 0.282 0 :;:,- "' (I) KET171 Propylene .u.., !2.

Ketoprofen 10% 7 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.031 0.093~ ""'' ;a KET171 Propylene "' C Ketoprofen 10% 8 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 4 1 0.041 0.123 0 1D "' KET171 Propylene 0 N I Ketoprofen 10% 9 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.027 0.081 0 ;0o) "' KET172 Propylene ,.I . 0 Ketoprofen 10% 0 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 0.106 0.318 ,.. ► KET172 Propylene C Ketoprofen 10% 1 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.067 0.201 KET172 Propylene Ketoprofen 10% 2 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.029 0.087 KET172 Propylene Ketoprofen 10% 3 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-dneole Yes 4 2 0.02 0.06 KET172 Propylene Ketoprofen 10% 4 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-clneole Yes 6 2 0.052 0.156 KET172 Propylene Ketoprofen 10% 5 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.054 0.162 KET172 Propylene ""d Ketoprofen 10% 6 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-clneole Yes 0.5 3 0.088 0.264 (") '"3 KET172 Propylene s;;: Ketoprofen 10% 7 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 2 3 0.023 0.069 KET172 Propylene ~ N Ketoprofen 10% 8 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.022 0.066 0 KET172 Propylene ""' QC) Ketoprofen 10% 9 KET113 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.016 0.048 -0 KET173 Propylene 3.5% 1,8- 0 Ketoprofen 10% 0 KET113 Ethanol glycol 30:70 Eucalyptus oil cineole Yes 8 3 0.021 0.063 N KET173 Propylene Ul Ul Ketoprofen 10% 1 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.291 0.873 KET173 Propylene ~ Ketoprofen 10% 2 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.03 0.09 0 KET173 Propylene N Ketoprofen 10% 3K ET173 KET114 Ethanol gPlryocpoyl lene 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.05 0.15 -"10", 0' Ketoprofen 10% 4 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.052 0.156 ""' KET173 Propylene w""' Ketoprofen 10% 5 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 1 0.655 1.965 0'I N KET173 Propylene Ul Ketoprofen 10% 6 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.029 0.087 KET173 Propylene Ketoprofen 10% 7 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.109 0.327 KET173 Propylene Ketoprofen 10% 8 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 4 2 0.088 0.264 KET173 Propylene Ketoprofen 10% 9 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.175 0.525 KET174 Propylene Ketoprofen 10% 0 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.589 1.767 en KET174 Propylene C Ketoprofen 10% 1 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.037 0.111 cr !!l. KET174 Propylene e Ketoprofen 10% 2 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.043 0.129 ~ ro KET174 Propylene 0 en Ketoprofen 10% 3 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.142 0.426 "0 ' :;:,- Propylene "' (I) KET174 .u.., !2.

Ketoprofen 10% 4 KET114 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 3 1.23 3.69~ ""'' ;a KET174 Propylene 3.5% 1,8- "' C Ketoprofen 10% 5 KET114 Ethanol glycol 50:50 Eucalyptus oil cineole No 8 3 2.713 8.139 0 1D "' KET174 Propylene 0 N I Ketoprofen 10% 6 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.204 0.612 0 ;0o) "' KET174 Propylene ,.I . 0 Ketoprofen 10% 7 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.127 0.381 ,.. ► KET174 Propylene C Ketoprofen 10% 8 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.042 0.126 KET174 Propylene Ketoprofen 10% 9 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.089 0.267 KET175 Propylene Ketoprofen 10% 0 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-dneole Yes 8 1 0.138 0.414 KET175 Propylene Ketoprofen 10% 1 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-clneole Yes 0.5 2 0.128 0.384 KET175 Propylene Ketoprofen 10% 2 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.094 0.282 KET175 Propylene ""d Ketoprofen 10% 3 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-clneole Yes 4 2 0.067 0.201 (") '"3 KET175 Propylene s;;: Ketoprofen 10% 4 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 6 2 0.051 0.153 KET175 Propylene ~ N Ketoprofen 10% 5 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.218 0.654 0 KET175 Propylene ""' QC) Ketoprofen 10% 6 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.024 0.072 -0 KET175 Propylene 0 Ketoprofen 10% 7 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.036 0.108 N KET175 Propylene Ul Ul Ketoprofen 10% 8 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.023 0.069 KET175 Propylene ~ Ketoprofen 10% 9 KET115 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.03 0.09 0 KET176 Propylene 3.5% 1,8- N Ketoprofen 10% 0K ET176 KET115 Ethanol gPlryocpoyl lene 50:50 Eucalyptus oil cineole Yes 8 3 0.58 1.74 -"10", 0' Ketoprofen 10% 1 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 1 0.093 0.279 """"'' KET176 Propylene w Ketoprofen 10% 2 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.836 2.508 0'I N KET176 Propylene Ul Ketoprofen 10% 3 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 4 1 12.264 36.792 KET176 Propylene Ketoprofen 10% 4 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 16.074 48.222 KET176 Propylene Ketoprofen 10% 5 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 17.972 53.916 KET176 Propylene Ketoprofen 10% 6 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.021 0.063 KET176 Propylene Ketoprofen 10% 7 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.077 0.231 en KET176 Propylene C Ketoprofen 10% 8 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.264 0.792 cr !!l. KET176 Propylene e Ketoprofen 10% 9 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.665 1.995 ~ ro KET177 Propylene 0 l.,J en Ketoprofen 10% 0 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 8 2 1.635 4.905 0 :;:,- "' (I) KET177 Propylene .u.., !2.

Ketoprofen 10% 1 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.026 0.078"i,. ""'' ;a KET177 Propylene "' C Ketoprofen 10% 2 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 2 3 0.042 0.126 0 1D "' KET177 Propylene 0 N I Ketoprofen 10% 3 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.48 1.44 0 ;0o) "' KET177 Propylene ,.I . 0 Ketoprofen 10% 4 KET116 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 2.102 6.306 ,.. ► KET177 Propylene 3.5% 1,8- C Ketoprofen 10% 5 KET116 Ethanol glycol 70:30 Eucalyptus oil cineole No 8 3 4.722 14.166 KET177 Propylene Ketoprofen 20% 6 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.027 0.081 KET177 Propylene Ketoprofen 20% 7 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.029 0.087 KET177 Propylene Ketoprofen 20% 8 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-clneole No 4 1 0.046 0.138 KET177 Propylene Ketoprofen 20% 9 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.12 0.36 KET178 Propylene ""d (") Ketoprofen 20% 0 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-clneole No 8 1 0.364 1.092 '"3 KET178 Propylene s;;: Ketoprofen 20% 1 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.029 0.087 KET178 Propylene ~ N Ketoprofen 20% 2 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.02 0.06 0 KET178 Propylene "Q"C') Ketoprofen 20% 3 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.024 0.072 -0 KET178 Propylene 0 Ketoprofen 20% 4 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.063 0.189 N KET178 Propylene Ul Ul Ketoprofen 20% 5 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.498 1.494 KET178 Propylene ~ Ketoprofen 20% 6 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.024 0.072 0 KET178 Propylene N Ketoprofen 20% 7K ET178 KET117 Ethanol gPlryocpoyl lene 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 3 O.D35 0.105 -"10", 0' Ketoprofen 20% 8 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.095 0.285 ""' KET178 Propylene w""' Ketoprofen 20% 9 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.581 1.743 0'I N KET179 Propylene Ul Ketoprofen 20% 0 KET117 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole No 8 3 1.776 5.328 KET179 Propylene Ketoprofen 20% 1 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.032 0.096 KET179 Propylene Ketoprofen 20% 2 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 2 1 0.016 0.048 KET179 Propylene Ketoprofen 20% 3 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.02 0.06 KET179 Propylene Ketoprofen 20% 4 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.251 0.753 en KET179 Propylene C Ketoprofen 20% 5 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 1.298 3.894 cr !!l. KET179 Propylene e Ketoprofen 20% 6 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.022 0.066 ~ ro KET179 Propylene 0 en Ketoprofen 20% 7 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.022 0.066 "0 ' :;:,- Propylene "' (I) KET179 .u.., !2.

Ketoprofen 20% 8 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.017 0.051~ ""'' ;a KET179 Propylene "' C Ketoprofen 20% 9 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 6 2 0.028 0.084 0 1D "' KET180 Propylene 0 N I Ketoprofen 20% 0 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.587 1.761 0 ;0o) "' KET180 Propylene ,.I . 0 Ketoprofen 20% 1 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.042 0.126 ,.. ► KET180 Propylene C Ketoprofen 20% 2 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.039 0.117 KET180 Propylene Ketoprofen 20% 3 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.042 0.126 KET180 Propylene Ketoprofen 20% 4 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.045 0.135 KET180 Propylene Ketoprofen 20% 5 KET118 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 3 0.157 0.471 KET180 Propylene Ketoprofen 20% 6 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.035 0.105 KET180 Propylene ""d Ketoprofen 20% 7 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-clneole No 2 1 0.169 0.507 (") '"3 KET180 Propylene s;;: Ketoprofen 20% 8 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 4 1 0.676 2.028 KET180 Propylene ~ N Ketoprofen 20% 9 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 2.562 7.686 0 KET181 Propylene ""' QC) Ketoprofen 20% 0 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 1 6.732 20.196 -0 KET181 Propylene 0 Ketoprofen 20% 1 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.031 0.093 0 N KET181 Propylene Ul Ketoprofen 20% 2 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.027 0.081 Ul KET181 Propylene ~ Ketoprofen 20% 3 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.051 0.153 0 KET181 Propylene N Ketoprofen 20% 4K ET181 KET119 Ethanol gPlryocpoyl lene 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.154 0.462 -"10", 0' Ketoprofen 20% 5 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.591 1.773 ""' KET181 Propylene w""' Ketoprofen 20% 6 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.024 0.072 0'I N KET181 Propylene Ul Ketoprofen 20% 7 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 2 3 0.031 0.093 KET181 Propylene Ketoprofen 20% 8 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.027 0.081 KET181 Propylene Ketoprofen 20% 9 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 6 3 0.055 0.165 KET182 Propylene Ketoprofen 20% 0 KET119 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 3 0.245 0.735 KET182 Propylene Ketoprofen 20% 1 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.026 0.078 en KET182 Propylene C Ketoprofen 20% 2 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.025 0.075 cr !!l. KET182 Propylene e Ketoprofen 20% 3 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.019 0.057 ~ ro KET182 Propylene 0 en Ketoprofen 20% 4 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.035 0.105 "0 ' :;:,- Propylene "' (I) KET182 .u.., !2.

Ketoprofen 20% 5 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 0.079 0.237~ ""'' ;a KET182 Propylene "' C Ketoprofen 20% 6 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 0.5 2 0.041 0.123 0 1D "' KET182 Propylene 0 N I Ketoprofen 20% 7 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.031 0.093 0 ;0o) "' KET182 Propylene ,.I . 0 Ketoprofen 20% 8 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.039 0.117 ,.. ► KET182 Propylene C Ketoprofen 20% 9 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 0.024 0.072 KET183 Propylene Ketoprofen 20% 0 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.067 0.201 KET183 Propylene Ketoprofen 20% 1 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.029 0.087 KET183 Propylene Ketoprofen 20% 2 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.025 0.075 KET183 Propylene Ketoprofen 20% 3 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.027 0.081 KET183 Propylene ""d Ketoprofen 20% 4 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-clneole Yes 6 3 0.022 0.066 (") '"3 KET183 Propylene s;;: Ketoprofen 20% 5 KET120 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 8 3 0.106 0.318 KET183 Propylene ~ N Ketoprofen 20% 6 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.117 0 KET183 Propylene ""' QC) Ketoprofen 20% 7 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.06 -0 KET183 Propylene 0 Ketoprofen 20% 8 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.279 0 N KET183 Propylene Ul Ketoprofen 20% 9 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 2.091 Ul KET184 Propylene ~ Ketoprofen 20% 0 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 10.968 0 KET184 Propylene N Ketoprofen 20% 1K ET184 KET121 Ethanol gPlryocpoyl lene 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.135 -"10", 0' Ketoprofen 20% 2 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.108 ""' KET184 Propylene w""' Ketoprofen 20% 3 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.219 0'I N KET184 Propylene Ul Ketoprofen 20% 4 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 6 2 1.458 KET184 Propylene Ketoprofen 20% 5 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 7.125 KET184 Propylene Ketoprofen 20% 6 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 3 0.117 KET184 Propylene Ketoprofen 20% 7 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.168 KET184 Propylene Ketoprofen 20% 8 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 1.236 en KET184 Propylene C Ketoprofen 20% 9 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 6.642 cr !!l. KET185 Propylene e Ketoprofen 20% 0 KET121 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 3 11.982 ~ ro KET185 Propylene 0 en Ketoprofen 30% 1 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.034 0.102 "0 ' :;:,- Propylene "' (I) KET185 .u.., !2.

Ketoprofen 30% 2 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.015 0.045 ~ ""'' ;a KET185 Propylene "' C Ketoprofen 30% 3 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole No 4 1 0.031 0.093 0 1D "' KET185 Propylene 0 N I Ketoprofen 30% 4 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.036 0.108 0 ;0o) "' KET185 Propylene ,.I . 0 Ketoprofen 30% 5 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 1 0.653 1.959 ,.. ► KET185 Propylene C Ketoprofen 30% 6 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.032 0.096 KET185 Propylene Ketoprofen 30% 7 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.032 0.096 KET185 Propylene Ketoprofen 30% 8 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.099 0.297 KET185 Propylene Ketoprofen 30% 9 KETlZZ Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.017 0.051 KET186 Propylene Ketoprofen 30% 0 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.082 0.246 KET186 Propylene ""d Ketoprofen 30% 1 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-clneole No 0.5 3 0.044 0.132 (") '"3 KET186 Propylene s;;: Ketoprofen 30% 2 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole No 2 3 0.018 0.054 KET186 Propylene ~ N Ketoprofen 30% 3 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.026 0.078 0 KET186 Propylene ""' QC) Ketoprofen 30% 4 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.019 0.057 -0 KET186 Propylene 0 Ketoprofen 30% 5 KET122 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 3 0.083 0.249 0 N KET186 Propylene Ul Ketoprofen 30% 6 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.031 0.093 Ul KET186 Propylene ~ Ketoprofen 30% 7 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.017 0.051 0 KET186 Propylene N Ketoprofen 30% 8K ET186 KET123 Ethanol gPlryocpoyl lene 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.027 0.081 -"10", 0' Ketoprofen 30% 9 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.029 0.087 ""' KET187 Propylene w""' Ketoprofen 30% 0 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 0.122 0.366 0'I N KET187 Propylene Ul Ketoprofen 30% 1 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 0.5 2 0.046 0.138 KET187 Propylene Ketoprofen 30% 2 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.021 0.063 KET187 Propylene Ketoprofen 30% 3 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 4 2 0.023 0.069 KET187 Propylene Ketoprofen 30% 4 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 0.019 0.057 KET187 Propylene Ketoprofen 30% 5 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.028 0.084 en KET187 Propylene C Ketoprofen 30% 6 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.022 0.066 cr !!l. KET187 Propylene e Ketoprofen 30% 7 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.02 0.06 ~ ro KET187 Propylene 0 en Ketoprofen 30% 8 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.018 0.054 "0 ' :;:,- Propylene "' (I) KET187 .u.., !2.

Ketoprofen 30% 9 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.02 0.06~ ""'' ;a KET188 Propylene "' C Ketoprofen 30% 0 KET123 Ethanol glycol 30:70 Eucalyptus oil 3.5% 118-cineole Yes 8 3 0.097 0.291 0 1D "' KET188 Propylene 0 N I Ketoprofen 30% 1 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.021 0.063 0 ;0o) "' KET188 Propylene ,.I . 0 Ketoprofen 30% 2 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.035 0.105 ,.. ► KET188 Propylene C Ketoprofen 30% 3 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.023 0.069 KET188 Propylene Ketoprofen 30% 4 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.087 0.261 KET188 Propylene Ketoprofen 30% 5 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.363 4.089 KET188 Propylene Ketoprofen 30% 6 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.04 0.12 KET188 Propylene Ketoprofen 30% 7 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.025 0.075 KET188 Propylene ""d Ketoprofen 30% 8 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-clneole No 4 2 0.023 0.069 (") '"3 KET188 Propylene s;;: Ketoprofen 30% 9 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole No 6 2 0.086 0.258 KET189 Propylene ~ N Ketoprofen 30% 0 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.527 1.581 0 KET189 Propylene ""' QC) Ketoprofen 30% 1 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.028 0.084 -0 KET189 Propylene 0 Ketoprofen 30% 2 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.024 0.072 0 N KET189 Propylene Ul Ketoprofen 30% 3 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.026 O.D78 Ul KET189 Propylene ~ Ketoprofen 30% 4 KET124 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.071 0.213 0 KET189 Propylene N Ketoprofen 30% 5K ET189 KET124 Ethanol gPlryocpoyl lene 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 3 0.877 2.631 -"10", 0' Ketoprofen 30% 6 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.028 0.084 ""' KET189 Propylene w""' Ketoprofen 30% 7 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.028 0.084 0'I N KET189 Propylene Ul Ketoprofen 30% 8 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 4 1 0.02 0.06 KET189 Propylene Ketoprofen 30% 9 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.039 0.117 KET190 Propylene Ketoprofen 30% 0 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 8 1 0.251 0.753 KET190 Propylene Ketoprofen 30% 1 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.025 O.D75 KET190 Propylene Ketoprofen 30% 2 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.178 0.534 en KET190 Propylene C Ketoprofen 30% 3 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.017 0.051 cr !!l. KET190 Propylene e Ketoprofen 30% 4 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 0.026 0.078 ~ ro KET190 Propylene 0 en Ketoprofen 30% 5 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 0.474 1.422 "0 ' :;:,- Propylene "' (I) KET190 .u.., !2.

Ketoprofen 30% 6 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.02 0.06~ ""'' ;a KET190 Propylene "' C Ketoprofen 30% 7 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 118-cineole Yes 2 3 0.035 0.105 0 1D "' KET190 Propylene 0 N I Ketoprofen 30% 8 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.02 0.06 0 ;0o) "' KET190 Propylene ,.I . 0 Ketoprofen 30% 9 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.023 0.069 ,.. ► KET191 Propylene C Ketoprofen 30% 0 KET125 Ethanol glycol 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 3 0.255 0.765 KET191 Propylene Ketoprofen 30% 1 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.026 0.078 KET191 Propylene Ketoprofen 30% 2 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.028 0.084 KET191 Propylene Ketoprofen 30% 3 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.047 0.141 KET191 Propylene Ketoprofen 30% 4 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.967 2.901 KET191 Propylene ""d Ketoprofen 30% 5 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-clneole No 8 1 3.753 11.259 (") '"3 KET191 Propylene s;;: Ketoprofen 30% 6 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.03 0.09 KET191 Propylene ~ N Ketoprofen 30% 7 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.046 0.138 0 KET191 Propylene ""' QC) Ketoprofen 30% 8 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.031 0.093 -0 KET191 Propylene 0 Ketoprofen 30% 9 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.047 0.141 0 N KET192 Propylene Ul Ketoprofen 30% 0 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.217 0.651 Ul KET192 Propylene ~ Ketoprofen 30% 1 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.05 0.15 0 KET192 Propylene N Ketoprofen 30% K2E T192 KET126 Ethanol gPlryocpoyl lene 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.027 0.081 -"10", 0' Ketoprofen 30% 3 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.032 0.096 ""' KET192 Propylene w""' Ketoprofen 30% 4 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.09 0.27 0'I N KET192 Propylene Ul Ketoprofen 30% 5 KET126 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 8 3 1.329 3.987 KET192 Propylene Ketoprofen 10% 6 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.013 0.039 KET192 Propylene Ketoprofen 10% 7 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole Yes 2 1 0.012 0.036 KET192 Propylene Ketoprofen 10% 8 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.053 0.159 KET192 Propylene Ketoprofen 10% 9 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.307 0.921 en KET193 Propylene C Ketoprofen 10% 0 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 1.71 5.13 cr !!l. KET193 Propylene e Ketoprofen 10% 1 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.024 0.072 ~ ro KET193 Propylene 0 en Ketoprofen 10% 2 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.469 1.407 "0 ' :;:,- Propylene "' (I) KET193 u, 4.101~ ... !2.

Ketoprofen 10% 3 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 1.367 ""'' ;a KET193 Propylene 0 "' C Ketoprofen 10% 4 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole Yes 6 2 4.517 13.551 0 1D "' KET193 Propylene 0 N I Ketoprofen 10% 5 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 6.107 18.321 0 ;0o) "' KET193 Propylene ,.I . 0 Ketoprofen 10% 6 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.008 0.024 ,.. ► KET193 Propylene C Ketoprofen 10% 7 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.024 0.072 KET193 Propylene Ketoprofen 10% 8 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.056 0.168 KET193 Propylene Ketoprofen 10% 9 KET127 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.395 1.185 KET194 Propylene 3.5% 1,8- Ketoprofen 10% 0 KET127 Ethanol glycol 70:30 Eucalyptus oil cineole Yes 8 3 1.323 3.969 KET194 lsopropyl Ketoprofen 10% 1 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.028 0.084 KET194 lsopropyl ""d Ketoprofen 10% 2 KET128 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 118-clneole No 2 1 0.103 0.309 (") '"3 KET194 lsopropyl s;;: Ketoprofen 10% 3 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 4 1 0.064 0.192 KET194 lsopropyl ~ N Ketoprofen 10% 4 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.088 0.264 0 KET194 lsopropyl ""' QC) Ketoprofen 10% 5 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 1 0.569 1.707 -0 KET194 lsopropyl 0 Ketoprofen 10% 6 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.284 0.852 N KET194 lsopropyl Ul Ul Ketoprofen 10% 7 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 2.64 7.92 KET194 lsopropyl ~ Ketoprofen 10% 8 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 2 8.094 24.282 0 KET194 lsopropyl N Ketoprofen 10% 9K ET195 KET128 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 2 12.799 38.397 -"10", 0' Ketoprofen 10% 0 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 17.165 51.495 ""' KET195 lsopropyl w""' Ketoprofen 10% 1 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.069 0.207 0'I N KET195 lsopropyl Ul Ketoprofen 10% 2 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 2 3 0.206 0.618 KET195 lsopropyl Ketoprofen 10% 3 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.484 1.452 KET195 lsopropyl Ketoprofen 10% 4 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 6 3 0.957 2.871 KET195 lsopropyl Ketoprofen 10% 5 KET128 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 3 1.397 4.191 KET195 lsopropyl Ketoprofen 10% 6 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.043 0.129 en KET195 lsopropyl C Ketoprofen 10% 7 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.265 0.795 cr !!l. KET195 lsopropyl e Ketoprofen 10% 8 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 1.159 3.477 ~ ro KET195 lsopropyl 0 en Ketoprofen 10% 9 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 2.383 7.149 "0 ' :;:,- lsopropyl "' (I) KET196 u, ll.523~ ... !2.

Ketoprofen 10% 0 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 3.841 ""'' ;a KET196 lsopropyl ""' "' C Ketoprofen 10% 1 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 0.5 2 0.027 0.081 0 1D "' KET196 lsopropyl 0 N I Ketoprofen 10% 2 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 4.539 13.617 0 ;0o) "' KET196 lsopropyl ,.I . 0 Ketoprofen 10% 3 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 8.846 26.538 ,.. ► KET196 lsopropyl C Ketoprofen 10% 4 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 12.655 37.965 KET196 lsopropyl Ketoprofen 10% 5 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 14.733 44.199 KET196 lsopropyl Ketoprofen 10% 6 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.035 0.105 KET196 lsopropyl Ketoprofen 10% 7 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.277 0.831 KET196 lsopropyl Ketoprofen 10% 8 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.519 1.557 KET196 lsopropyl ""d Ketoprofen 10% 9 KET129 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 1,8-clneole Yes 6 3 1.001 3.003 (") '"3 KET197 lsopropyl s;;: Ketoprofen 10% 0 KET129 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 8 3 1.352 4.056 KET197 lsopropyl ~ N Ketoprofen 10% 1 KET130 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 O.Q35 0.105 0 KET197 lsopropyl ""' QC) Ketoprofen 10% 2 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.111 0.333 -0 KET197 lsopropyl 0 Ketoprofen 10% 3 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.2 0.6 0 N KET197 lsopropyl Ul Ketoprofen 10% 4 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.259 0.777 Ul KET197 lsopropyl ~ Ketoprofen 10% 5 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.024 3.072 0 KET197 lsopropyl N Ketoprofen 10% 6K ET197 KET130 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.156 0.468 -"10", 0' Ketoprofen 10% 7 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.267 0.801 ""' KET197 lsopropyl w""' Ketoprofen 10% 8 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.187 0.561 0'I N KET197 lsopropyl Ul Ketoprofen 10% 9 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 6 2 3.136 9.408 KET198 lsopropyl Ketoprofen 10% 0 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.384 1.152 KET198 lsopropyl Ketoprofen 10% 1 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 0.5 3 0.067 0.201 KET198 lsopropyl Ketoprofen 10% 2 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.1 0.3 KET198 lsopropyl Ketoprofen 10% 3 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.077 0.231 en KET198 lsopropyl C Ketoprofen 10% 4 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 3 3.288 9.864 cr !!l. KET198 lsopropyl e Ketoprofen 10% 5 KET130 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 3 0.76 2.28 ~ ro KET198 lsopropyl 0 en Ketoprofen 10% 6 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.043 0.129 "0 ' :;:,- lsopropyl "' (I) KET198 u, 0.156~ ... !2.

Ketoprofen 10% 7 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.052 ""'' ;a KET198 lsopropyl N "' C Ketoprofen 10% 8 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 4 1 0.072 0.216 0 1D "' KET198 lsopropyl 0 N I Ketoprofen 10% 9 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 1.252 3.756 0 ;0o) "' KET199 lsopropyl ,.I . 0 Ketoprofen 10% 0 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 0.467 1.401 ,.. ► KET199 lsopropyl C Ketoprofen 10% 1 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.031 0.093 KET199 lsopropyl Ketoprofen 10% 2 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.907 2.721 KET199 lsopropyl Ketoprofen 10% 3 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 1.581 4.743 KET199 lsopropyl Ketoprofen 10% 4 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 2.151 6.453 KET199 lsopropyl Ketoprofen 10% 5 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 5.121 15.363 KET199 lsopropyl ""d Ketoprofen 10% 6 KET131 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-clneole Yes 0.5 3 0.039 0.117 (") '"3 KET199 lsopropyl s;;: Ketoprofen 10% 7 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 2 3 0.077 0.231 KET199 lsopropyl ~ N Ketoprofen 10% 8 KET131 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 2.376 7.128 0 KET199 lsopropyl ""' QC) Ketoprofen 10% 9 KET131 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.179 0.537 -0 KET200 lsopropyl 3.5% 1,8- 0 Ketoprofen 10% 0 KET131 Ethanol myristate 50:50 Eucalyptus oil cineole Yes 8 3 3.418 10.254 0 N KET200 Propylene Ul Ul Ketoprofen 20% 1 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.026 0.078 KET200 Propylene ~ Ketoprofen 20% 2 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.01 0.03 0 KET200 Propylene N Ketoprofen 20% 3K ET200 KET132 Ethanol gPlryocpoyl lene 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.096 0.288 -"10", 0' Ketoprofen 20% 4 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.072 0.216 ""' KET200 Propylene w""' Ketoprofen 20% 5 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.178 3.534 0'I N KET200 Propylene Ul Ketoprofen 20% 6 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.013 0.039 KET200 Propylene Ketoprofen 20% 7 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.03 0.09 KET200 Propylene Ketoprofen 20% 8 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 4 2 0.249 0.747 KET200 Propylene Ketoprofen 20% 9 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.184 0.552 KET201 Propylene Ketoprofen 20% 0 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 1.384 4.152 en KET201 Propylene C Ketoprofen 20% 1 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.03 0.09 cr !!l. KET201 Propylene e Ketoprofen 20% 2 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.01 0.03 ~ ro KET201 Propylene 0 en Ketoprofen 20% 3 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.475 1.425 "0 ' :;:,- Propylene "' (I) KET201 u, l.44~ ... !2.

Ketoprofen 20% 4 KET132 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 0.48 ""'' ;a KET201 Propylene 3.5% 1,8- w "' C Ketoprofen 20% 5 KET132 Ethanol glycol 70:30 Eucalyptus oil cineole No 8 3 1.557 4.671 0 1D "' KET201 lsopropyl 0 N I Ketoprofen 20% 6 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.053 0.159 0 ;0o) "' KET201 lsopropyl ,.I . 0 Ketoprofen 20% 7 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.054 0.162 ,.. ► KET201 lsopropyl C Ketoprofen 20% 8 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.183 0.549 KET201 lsopropyl Ketoprofen 20% 9 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.558 1.674 KET202 lsopropyl Ketoprofen 20% 0 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-dneole No 8 1 1.459 4.377 KET202 lsopropyl Ketoprofen 20% 1 KET133 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 118-clneole No 0.5 2 0.029 0.087 KET202 lsopropyl Ketoprofen 20% 2 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.069 0.207 KET202 lsopropyl ""d Ketoprofen 20% 3 KET133 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 118-clneole No 4 2 0.022 0.066 (") '"3 KET202 lsopropyl s;;: Ketoprofen 20% 4 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 6 2 0.228 0.684 KET202 lsopropyl ~ N Ketoprofen 20% 5 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.596 1.788 0 KET202 lsopropyl ""' QC) Ketoprofen 20% 6 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.043 0.129 -0 KET202 lsopropyl 0 Ketoprofen 20% 7 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.262 0.786 N KET202 lsopropyl Ul Ul Ketoprofen 20% 8 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.086 0.258 KET202 lsopropyl ~ Ketoprofen 20% 9 KET133 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 3 5.51 16.53 0 KET203 lsopropyl N Ketoprofen 20% 0K ET203 KET133 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 3 11.718 35.154 -"10", 0' Ketoprofen 20% 1 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.057 0.171 ""' KET203 lsopropyl w""' Ketoprofen 20% 2 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.119 0.357 0'I N KET203 lsopropyl Ul Ketoprofen 20% 3 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 4 1 1.608 4.824 KET203 lsopropyl Ketoprofen 20% 4 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.517 1.551 KET203 lsopropyl Ketoprofen 20% 5 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 8 1 1.164 3.492 KET203 lsopropyl Ketoprofen 20% 6 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.05 0.15 KET203 lsopropyl Ketoprofen 20% 7 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.109 0.327 en KET203 lsopropyl C Ketoprofen 20% 8 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.208 0.624 cr !!l. KET203 lsopropyl e Ketoprofen 20% 9 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 0.719 2.157 ~ ro KET204 lsopropyl 0 en Ketoprofen 20% 0 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 1.958 5.874 "0 ' :;:,- lsopropyl "' (I) KET204 u, 0.228~ ... !2.

Ketoprofen 20% 1 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.076 ""'' ;a KET204 lsopropyl .. "' C Ketoprofen 20% 2 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 2 3 0.058 0.174 0 1D "' KET204 lsopropyl 0 N I Ketoprofen 20% 3 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.195 0.585 0 ;0o) "' KET204 lsopropyl ,.I . 0 Ketoprofen 20% 4 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 1.544 4.632 ,.. ► KET204 lsopropyl C Ketoprofen 20% 5 KET134 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 3 4.13 12.39 KET204 lsopropyl Ketoprofen 20% 6 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.053 0.159 KET204 lsopropyl Ketoprofen 20% 7 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.054 0.162 KET204 lsopropyl Ketoprofen 20% 8 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.183 0.549 KET204 lsopropyl Ketoprofen 20% 9 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.558 1.674 KET205 lsopropyl ""d Ketoprofen 20% 0 KET135 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-clneole No 8 1 1.459 4.377 (") '"3 KET205 lsopropyl s;;: Ketoprofen 20% 1 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.029 0.087 KET205 lsopropyl ~ N Ketoprofen 20% 2 KET135 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.069 0.207 0 KET205 lsopropyl ""' QC) Ketoprofen 20% 3 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.022 0.066 -0 KET205 lsopropyl 0 Ketoprofen 20% 4 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.228 0.684 0 N KET205 lsopropyl Ul Ketoprofen 20% 5 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.596 1.788 Ul KET205 lsopropyl ~ Ketoprofen 20% 6 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.043 0.129 0 KET205 lsopropyl N Ketoprofen 20% 7K ET205 KET135 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.262 0.786 -"10", 0' Ketoprofen 20% 8 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.086 0.258 ""' KET205 lsopropyl w""' Ketoprofen 20% 9 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 3 5.51 16.53 0'I N KET206 lsopropyl Ul Ketoprofen 20% 0 KET135 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 8 3 11.718 35.154 KET206 lsopropyl Ketoprofen 20% 1 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.057 0.171 KET206 lsopropyl Ketoprofen 20% 2 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 2 1 0.119 0.357 KET206 lsopropyl Ketoprofen 20% 3 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 1.608 4.824 KET206 lsopropyl Ketoprofen 20% 4 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.517 1.551 en KET206 lsopropyl C Ketoprofen 20% 5 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 1.164 3.492 cr !!l. KET206 lsopropyl e Ketoprofen 20% 6 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.05 0.15 ~ ro KET206 lsopropyl 0 en Ketoprofen 20% 7 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.109 0.327 "0 ' :;:,- lsopropyl "' (I) KET206 u, 0.624~ ... !2.

Ketoprofen 20% 8 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.208 ""'' ;a KET206 lsopropyl Ul "' C Ketoprofen 20% 9 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 6 2 0.719 2.157 0 1D "' KET207 lsopropyl 0 N I Ketoprofen 20% 0 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 1.958 5.874 0 ;0o) "' KET207 lsopropyl ,.I . 0 Ketoprofen 20% 1 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.076 0.228 ,.. ► KET207 lsopropyl C Ketoprofen 20% 2 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.058 0.174 KET207 lsopropyl Ketoprofen 20% 3 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.195 0.585 KET207 lsopropyl Ketoprofen 20% 4 KET136 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 1.544 4.632 KET207 lsopropyl 3.5% 1,8- Ketoprofen 20% 5 KET136 Ethanol myristate 50:50 Eucalyptus oil cineole Yes 8 3 4.13 12.39 KET207 Propylene Ketoprofen 30% 6 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.043 0.129 KET207 Propylene ""d Ketoprofen 30% 7 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-clneole No 2 1 0.013 0.039 (") '"3 KET207 Propylene s;;: Ketoprofen 30% 8 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 4 1 0.124 0.372 KET207 Propylene ~ N Ketoprofen 30% 9 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.233 0.699 0 KET208 Propylene ""' QC) Ketoprofen 30% 0 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 3.101 9.303 -0 KET208 Propylene 0 Ketoprofen 30% 1 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.012 0.036 N KET208 Propylene Ul Ul Ketoprofen 30% 2 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.01 0.03 KET208 Propylene ~ Ketoprofen 30% 3 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.499 1.497 0 KET208 Propylene N Ketoprofen 30% 4K ET208 KET137 Ethanol gPlryocpoyl lene 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.585 1.755 -"10", 0' Ketoprofen 30% 5 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 1.719 5.157 ""' KET208 Propylene w""' Ketoprofen 30% 6 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.017 0.051 0'I N KET208 Propylene Ul Ketoprofen 30% 7 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 2 3 0.008 0.024 KET208 Propylene Ketoprofen 30% 8 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.243 0.729 KET208 Propylene Ketoprofen 30% 9 KET137 Ethanol glycol 70:30 Eucalyptus oil 3.5% 118-cineole No 6 3 0.448 1.344 KET209 Propylene 3.5% 1,8- Ketoprofen 30% 0 KET137 Ethanol glycol 70:30 Eucalyptus oil cineole No 8 3 2.38 7.14 KET209 lsopropyl Ketoprofen 30% 1 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.065 0.195 en KET209 lsopropyl C Ketoprofen 30% 2 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.049 0.147 cr !!l. KET209 lsopropyl e Ketoprofen 30% 3 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.075 0.225 ~ ro KET209 lsopropyl 0 en Ketoprofen 30% 4 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1 "' 18-cineole No 6 1 0.146 0.438 0 :;:,- "' (I) KET209 lsopropyl u, !2. l.425~ ...

Ketoprofen 30% 5 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 1 0.475 ""'' ;a KET209 lsopropyl 0'I "' C Ketoprofen 30% 6 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.039 0.117 0 1D "' KET209 lsopropyl 0 N I Ketoprofen 30% 7 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.054 0.162 0 ;0o) "' KET209 lsopropyl ,.I . 0 Ketoprofen 30% 8 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.06 0.18 ,.. ► KET209 lsopropyl C Ketoprofen 30% 9 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.166 0.498 KET210 lsopropyl Ketoprofen 30% 0 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 8 2 0.638 1.914 KET210 lsopropyl Ketoprofen 30% 1 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-dneole No 0.5 3 0.039 0.117 KET210 lsopropyl Ketoprofen 30% 2 KET138 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 118-clneole No 2 3 0.042 0.126 KET210 lsopropyl Ketoprofen 30% 3 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.126 0.378 KET210 lsopropyl ""d Ketoprofen 30% 4 KET138 Ethanol myr!state 30:70 Eucalyptus oil 3.5% 118-clneole No 6 3 1.522 4.566 (") '"3 KET210 lsopropyl s;;: Ketoprofen 30% 5 KET138 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole No 8 3 6.056 18.168 KET210 lsopropyl ~ N Ketoprofen 30% 6 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.034 0.102 0 KET210 lsopropyl ""' QC) Ketoprofen 30% 7 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 3.448 10.344 -0 KET210 lsopropyl 0 Ketoprofen 30% 8 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 12.099 36.297 N KET210 lsopropyl Ul Ul Ketoprofen 30% 9 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 17.446 52.338 KET211 lsopropyl ~ Ketoprofen 30% 0 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 25.973 77.919 0 KET211 lsopropyl N Ketoprofen 30% 1K ET211 KET139 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.027 0.081 -"10", 0' Ketoprofen 30% 2 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.217 0.651 ""' KET211 lsopropyl w""' Ketoprofen 30% 3 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.867 2.601 0'I N KET211 lsopropyl Ul Ketoprofen 30% 4 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 6 2 1.673 5.019 KET211 lsopropyl Ketoprofen 30% 5 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 1.99 5.97 KET211 lsopropyl Ketoprofen 30% 6 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 118-cineole Yes 0.5 3 0.042 0.126 KET211 lsopropyl Ketoprofen 30% 7 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.083 0.249 KET211 lsopropyl Ketoprofen 30% 8 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.276 0.828 en KET211 lsopropyl C Ketoprofen 30% 9 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.816 2.448 cr !!l. KET212 lsopropyl e Ketoprofen 30% 0 KET139 Ethanol myristate 30:70 Eucalyptus oil 3.5% 1,8-cineole Yes 8 3 2.438 7.314 ~ ro KET212 lsopropyl 0 en Ketoprofen 30% 1 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.036 0.108 "0 ' :;:,- lsopropyl "' (I) KET212 u, ll.283~ ... !2.

Ketoprofen 30% 2 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 1 3.761 ""'' ;a KET212 lsopropyl -.,l "' C Ketoprofen 30% 3 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 4 1 11.055 33.165 0 1D "' KET212 lsopropyl 0 N I Ketoprofen 30% 4 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 1 24.874 74.622 0 ;0o) "' KET212 lsopropyl ,.I . 0 Ketoprofen 30% 5 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 1 39.875 119.625 ,.. ► KET212 lsopropyl C Ketoprofen 30% 6 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.043 0.129 KET212 lsopropyl Ketoprofen 30% 7 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.242 0.726 KET212 lsopropyl Ketoprofen 30% 8 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 2 1.335 4.005 KET212 lsopropyl Ketoprofen 30% 9 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 2 4.696 14.088 KET213 lsopropyl Ketoprofen 30% 0 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 2 10.407 31.221 KET213 lsopropyl ""d Ketoprofen 30% 1 KET140 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 118-clneole No 0.5 3 0.097 0.291 (") '"3 KET213 lsopropyl s;;: Ketoprofen 30% 2 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole No 2 3 0.201 0.603 KET213 lsopropyl ~ N Ketoprofen 30% 3 KET140 Ethanol myr!state 50:50 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.41 1.23 0 KET213 lsopropyl ""' QC) Ketoprofen 30% 4 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 6 3 2.04 6.12 -0 KET213 lsopropyl 0 Ketoprofen 30% 5 KET140 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole No 8 3 6.345 19.035 0 N KET213 lsopropyl Ul Ketoprofen 30% 6 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.065 0.195 Ul KET213 lsopropyl ~ Ketoprofen 30% 7 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.062 0.186 0 KET213 lsopropyl N Ketoprofen 30% 8K ET213 KET141 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 0.143 0.429 -"10", 0' Ketoprofen 30% 9 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.55 1.65 ""' KET214 lsopropyl w""' Ketoprofen 30% 0 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 1.574 4.722 0'I N KET214 lsopropyl Ul Ketoprofen 30% 1 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 0.5 2 0.042 0.126 KET214 lsopropyl Ketoprofen 30% 2 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.052 0.156 KET214 lsopropyl Ketoprofen 30% 3 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 4 2 0.263 0.789 KET214 lsopropyl Ketoprofen 30% 4 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 1.754 5.262 KET214 lsopropyl Ketoprofen 30% 5 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 5.928 17.784 en KET214 lsopropyl C Ketoprofen 30% 6 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.039 0.117 cr !!l. KET214 lsopropyl e Ketoprofen 30% 7 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.049 0.147 ~ ro KET214 lsopropyl 0 en Ketoprofen 30% 8 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.086 0.258 "0 ' :;:,- lsopropyl "' (I) KET214 u, l.518~ ... !2.

Ketoprofen 30% 9 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 0.506 ""'' ;a KET215 lsopropyl QC) "' C Ketoprofen 30% 0 KET141 Ethanol myristate 50:50 Eucalyptus oil 3.5% 118-cineole Yes 8 3 2.241 6.723 0 1D "' KET215 lsopropyl 0 N I Ketoprofen 10% 1 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.052 0.156 0 ;0o) "' KET215 lsopropyl ,.I . 0 Ketoprofen 10% 2 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 1.741 5.223 ,.. ► KET215 lsopropyl C Ketoprofen 10% 3 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 1 1.169 3.507 KET215 lsopropyl Ketoprofen 10% 4 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 1.245 3.735 KET215 lsopropyl Ketoprofen 10% 5 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.22 3.66 KET215 lsopropyl Ketoprofen 10% 6 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.133 0.399 KET215 lsopropyl Ketoprofen 10% 7 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.206 0.618 KET215 lsopropyl ""d Ketoprofen 10% 8 KET142 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 1,8-clneole No 4 2 0.514 1.542 (") '"3 KET215 lsopropyl s;;: Ketoprofen 10% 9 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 6 2 0.161 0.483 KET216 lsopropyl ~ N Ketoprofen 10% 0 KET142 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 3.91 11.73 0 KET216 lsopropyl ""' QC) Ketoprofen 10% 1 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 1.535 4.605 -0 KET216 lsopropyl 0 Ketoprofen 10% 2 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 3 0.063 0.189 0 N KET216 lsopropyl Ul Ketoprofen 10% 3 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.083 0.249 Ul KET216 lsopropyl ~ Ketoprofen 10% 4 KET142 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 1.223 3.669 0 KET216 lsopropyl N Ketoprofen 10% 5K ET216 KET142 Ethanol lmsoyprirsotaptyel 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 3 0.363 1.089 -1"0", 0' Ketoprofen 10% 6 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.048 0.144 ""' KET216 lsopropyl w""' Ketoprofen 10% 7 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.249 0.747 0'I N KET216 lsopropyl Ul Ketoprofen 10% 8 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 4 1 0.709 2.127 KET216 lsopropyl Ketoprofen 10% 9 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 1.007 3.021 KET217 lsopropyl Ketoprofen 10% 0 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 8 1 1.719 5.157 KET217 lsopropyl Ketoprofen 10% 1 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 0.061 0.183 KET217 lsopropyl Ketoprofen 10% 2 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 0.235 0.705 en KET217 lsopropyl C Ketoprofen 10% 3 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 1.562 4.686 cr !!l. KET217 lsopropyl e Ketoprofen 10% 4 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 2.804 8.412 ~ ro KET217 lsopropyl 0 en Ketoprofen 10% 5 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 4.219 12.657 "0 ' :;:,- lsopropyl "' (I) KET217 u, 0.168~ ... !2.

Ketoprofen 10% 6 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.056 ""'' ;a KET217 lsopropyl 1,0 "' C Ketoprofen 10% 7 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 2 3 0.767 2.301 0 1D "' KET217 lsopropyl 0 N I Ketoprofen 10% 8 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.088 0.264 0 ;0o) "' KET217 lsopropyl ,.I . 0 Ketoprofen 10% 9 KET143 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 2.793 8.379 ,.. ► KET218 lsopropyl 3.5% 1,8- C Ketoprofen 10% 0 KET143 Ethanol myristate 70:30 Eucalyptus oil cineole Yes 8 3 4.272 12.816 KET218 Propylene Ketoprofen 10% 1 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 1.347 4.041 KET218 Propylene Ketoprofen 10% 2 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-dneole No 2 1 1.532 4.596 KET218 Propylene Ketoprofen 10% 3 KET144 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-clneole No 4 1 1.375 4.125 KET218 Propylene Ketoprofen 10% 4 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 2.095 6.285 KET218 Propylene ""d Ketoprofen 10% 5 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-clneole No 8 1 6.049 18.147 (") '"3 KET218 Propylene s;;: Ketoprofen 10% 6 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-cineole No 0.5 2 0.079 0.237 KET218 Propylene ~ N Ketoprofen 10% 7 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.077 0.231 0 KET218 Propylene ""' QC) Ketoprofen 10% 8 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 2 0.073 0.219 -0 KET218 Propylene 0 Ketoprofen 10% 9 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 2 0.095 0.285 N KET219 Propylene Ul Ul Ketoprofen 10% 0 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 0.986 2.958 KET219 Propylene ~ Ketoprofen 10% 1 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.074 0.222 0 KET219 Propylene N Ketoprofen 10% K2E T219 KET144 Ethanol gPlryocpoyl lene 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.074 0.222 -"10", 0' Ketoprofen 10% 3 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 0.083 0.249 ""' KET219 Propylene w""' Ketoprofen 10% 4 KET144 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 3 0.161 0.483 0'I N KET219 Propylene 7.0% 118- Ul Ketoprofen 10% 5 KET144 Ethanol glycol 30:70 Eucalyptus oil cineole No 8 3 2.161 6.483 KET219 lsopropyl Ketoprofen 10% 6 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.043 0.129 KET219 lsopropyl Ketoprofen 10% 7 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.34 1.02 KET219 lsopropyl Ketoprofen 10% 8 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 1 0.356 1.068 KET219 lsopropyl Ketoprofen 10% 9 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 2.57 7.71 en KET220 lsopropyl C Ketoprofen 10% 0 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 1 3.6 10.8 cr !!l. KET220 lsopropyl e Ketoprofen 10% 1 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.047 0.141 ~ ro KET220 lsopropyl 0 en Ketoprofen 10% 2 KET145 Ethanol myristate 30:70 Eucalyptus oil 7. 0% 1 "' 18-cineole No 2 2 0.224 0.672 0 :;:,- "' (I) KET220 lsopropyl u, !2. 0.363= ...

Ketoprofen 10% 3 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 2 0.121 ""'' ;a KET220 lsopropyl 0 "' C Ketoprofen 10% 4 KET145 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 6 2 1.846 5.538 0 1D "' KET220 lsopropyl 0 N I Ketoprofen 10% 5 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 3.144 9.432 0 ;0o) "' KET220 lsopropyl ,.I . 0 Ketoprofen 10% 6 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.087 0.261 ,.. ► KET220 lsopropyl C Ketoprofen 10% 7 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.271 0.813 KET220 lsopropyl Ketoprofen 10% 8 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 1.639 4.917 KET220 lsopropyl Ketoprofen 10% 9 KET145 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-dneole No 6 3 0.621 1.863 KET221 lsopropyl 7.0% 1,8- Ketoprofen 10% 0 KET145 Ethanol myr!state 30:70 Eucalyptus oil cineole No 8 3 1.443 4.329 KET221 Propylene Ketoprofen 10% 1 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.047 0.141 KET221 Propylene ""d (") Ketoprofen 10% 2 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-clneole Yes 2 1 0.011 0.033 '"3 KET221 Propylene s;;: Ketoprofen 10% 3 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 0.022 0.066 KET221 Propylene ~ N Ketoprofen 10% 4 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.025 0.075 0 KET221 Propylene "Q"C') Ketoprofen 10% 5 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 0.168 0.504 -0 KET221 Propylene 0 Ketoprofen 10% 6 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.053 0.159 N KET221 Propylene Ul Ul Ketoprofen 10% 7 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.008 0.024 KET221 Propylene ~ Ketoprofen 10% 8 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 0.012 0.036 0 KET221 Propylene N Ketoprofen 10% 9K ET222 KET146 Ethanol gPlryocpoyl lene 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 0.021 0.063 -1"0", 0' Ketoprofen 10% 0 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 0.399 1.197 ""' KET222 Propylene w""' Ketoprofen 10% 1 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.015 0.045 0'I N KET222 Propylene Ul Ketoprofen 10% 2 KET146 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 2 3 0.007 0.021 KET222 Propylene Ketoprofen 10% 3 KET146 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.069 0.207 KET222 Propylene Ketoprofen 10% 4 KET146 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 6 3 0.01 0.03 KET222 Propylene 7.0% 1,8- Ketoprofen 10% 5 KET146 Ethanol glycol 30:70 Eucalyptus oil cineole Yes 8 3 0.049 0.147 KET222 lsopropyl Ketoprofen 20% 6 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 1 0.062 0.186 en KET222 lsopropyl C Ketoprofen 20% 7 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.231 0.693 cr !!l. KET222 lsopropyl e Ketoprofen 20% 8 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 1 0.195 0.585 ~ ro KET222 lsopropyl 0 l.,J en Ketoprofen 20% 9 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 6 1 0.441 1.323 0 :;:,- "' (I) KET223 lsopropyl u, !2. 3.357::: ...

Ketoprofen 20% 0 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.119 ""'' ;a KET223 lsopropyl ""' "' C Ketoprofen 20% 1 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 2 0.036 0.108 0 1D "' KET223 lsopropyl 0 N I Ketoprofen 20% 2 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 3.345 10.035 0 ;0o) "' KET223 lsopropyl ,.I . 0 Ketoprofen 20% 3 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.201 0.603 ,.. ► KET223 lsopropyl C Ketoprofen 20% 4 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 18.947 56.841 KET223 lsopropyl Ketoprofen 20% 5 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 2 27.13 81.39 KET223 lsopropyl Ketoprofen 20% 6 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-dneole No 0.5 3 0.045 0.135 KET223 lsopropyl Ketoprofen 20% 7 KET147 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 118-clneole No 2 3 0.118 0.354 KET223 lsopropyl Ketoprofen 20% 8 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.13 0.39 KET223 lsopropyl ""d Ketoprofen 20% 9 KET147 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 118-clneole No 6 3 2.423 7.269 (") '"3 KET224 lsopropyl s;;: Ketoprofen 20% 0 KET147 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 8 3 5.49 16.47 KET224 lsopropyl ~ N Ketoprofen 20% 1 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.042 0.126 0 KET224 lsopropyl ""' QC) Ketoprofen 20% 2 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 0.072 0.216 -0 KET224 lsopropyl 0 Ketoprofen 20% 3 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 1 10.198 30.594 N KET224 lsopropyl Ul Ul Ketoprofen 20% 4 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 0.368 1.104 KET224 lsopropyl ~ Ketoprofen 20% 5 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 1 0.764 2.292 0 KET224 lsopropyl N Ketoprofen 20% 6K ET224 KET148 Ethanol lmsoyprirsotaptyel 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 2 O.Q35 0.105 -"10", 0' Ketoprofen 20% 7 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 2.67 8.01 ""' KET224 lsopropyl w""' Ketoprofen 20% 8 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 0.987 2.961 0'I N KET224 lsopropyl Ul Ketoprofen 20% 9 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 6 2 13.131 39.393 KET225 lsopropyl Ketoprofen 20% 0 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 17.996 53.988 KET225 lsopropyl Ketoprofen 20% 1 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 0.5 3 0.03 0.09 KET225 lsopropyl Ketoprofen 20% 2 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.46 1.38 KET225 lsopropyl Ketoprofen 20% 3 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 0.206 0.618 en KET225 lsopropyl C Ketoprofen 20% 4 KET148 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 2.409 7.227 cr !!l. KET225 lsopropyl 3.5% 1,8- e Ketoprofen 20% 5 KET148 Ethanol myristate 70:30 Eucalyptus oil cineole Yes 8 3 5.535 16.605 ~ ro KET225 Propylene 0 en Ketoprofen 20% 6 KET149 Ethanol glycol 30:70 Eucalyptus oil 7. 0% 1 "' 18-cineole No 0.5 1 0.021 0.063 0 :;:,- "' (I) KET225 Propylene u, !2. 6.687= ...

Ketoprofen 20% 7 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 1 2.229 ""'' ;a KET225 Propylene N "' C Ketoprofen 20% 8 KET149 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-cineole No 4 1 9.642 28.926 0 1D "' KET225 Propylene 0 N I Ketoprofen 20% 9 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 7.797 23.391 0 ;0o) "' KET226 Propylene ,.I . 0 Ketoprofen 20% 0 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 1 25.76 77.28 ,.. ► KET226 Propylene C Ketoprofen 20% 1 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.008 0.024 KET226 Propylene Ketoprofen 20% 2 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.093 0.279 KET226 Propylene Ketoprofen 20% 3 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-dneole No 4 2 1.287 3.861 KET226 Propylene Ketoprofen 20% 4 KET149 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-clneole No 6 2 1.223 3.669 KET226 Propylene Ketoprofen 20% 5 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 7.323 21.969 KET226 Propylene ""d Ketoprofen 20% 6 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-clneole No 0.5 3 0.017 0.051 (") '"3 KET226 Propylene s;;: Ketoprofen 20% 7 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-cineole No 2 3 0.061 0.183 KET226 Propylene ~ N Ketoprofen 20% 8 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 0.12 0.36 0 KET226 Propylene ""' QC) Ketoprofen 20% 9 KET149 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 3 0.133 0.399 -0 KET227 Propylene 7.0% 1,8- 0 Ketoprofen 20% 0 KET149 Ethanol glycol 30:70 Eucalyptus oil cineole No 8 3 0.965 2.895 N KET227 lsopropyl Ul Ul Ketoprofen 20% 1 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.041 0.123 KET227 lsopropyl ~ Ketoprofen 20% 2 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.097 0.291 0 KET227 lsopropyl N Ketoprofen 20% 3K ET227 KET150 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 1 8.058 24.174 -"10", 0' Ketoprofen 20% 4 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 0.482 1.446 ""' KET227 lsopropyl w""' Ketoprofen 20% 5 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 1 1.472 4.416 0'I N KET227 lsopropyl Ul Ketoprofen 20% 6 KET150 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 0.5 2 0.033 0.099 KET227 lsopropyl Ketoprofen 20% 7 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.083 0.249 KET227 lsopropyl Ketoprofen 20% 8 KET150 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 4 2 8.576 25.728 KET227 lsopropyl Ketoprofen 20% 9 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 2 1.173 3.519 KET228 lsopropyl Ketoprofen 20% 0 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 2.574 7.722 en KET228 lsopropyl C Ketoprofen 20% 1 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.047 0.141 cr !!l. KET228 lsopropyl e Ketoprofen 20% 2 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.066 0.198 ~ ro KET228 lsopropyl 0 en Ketoprofen 20% 3 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 0.87 2.61 "0 ' :;:,- lsopropyl "' (I) KET228 u, 0.75= ... !2.

Ketoprofen 20% 4 KET150 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 3 0.25 ""'' ;a KET228 lsopropyl w "' C Ketoprofen 20% 5 KET150 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 8 3 1.015 3.045 0 1D "' KET228 Propylene 7.0% 1,8- 0 N I Ketoprofen 20% 6 KET151 Ethanol glycol 30:70 Eucalyptus oil cineole Yes 0.5 1 0.01 0.03 0 ;0o) "' KET228 Propylene ,.I . 0 Ketoprofen 20% 7 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.023 0.069 ,.. ► KET228 Propylene C Ketoprofen 20% 8 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 0.087 0.261 KET228 Propylene Ketoprofen 20% 9 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.046 0.138 KET229 Propylene Ketoprofen 20% 0 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-dneole Yes 8 1 0.388 1.164 KET229 Propylene Ketoprofen 20% 1 KET151 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-clneole Yes 0.5 2 0.009 0.027 KET229 Propylene Ketoprofen 20% 2 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.014 0.042 KET229 Propylene ""d Ketoprofen 20% 3 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-clneole Yes 4 2 0.046 0.138 (") '"3 KET229 Propylene s;;: Ketoprofen 20% 4 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-cineole Yes 6 2 0.027 0.081 KET229 Propylene ~ N Ketoprofen 20% 5 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 0.1 0.3 0 KET229 Propylene ""' QC) Ketoprofen 20% 6 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.073 0.219 -0 KET229 Propylene 0 Ketoprofen 20% 7 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 3 0.074 0.222 N KET229 Propylene Ul Ul Ketoprofen 20% 8 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.294 0.882 KET229 Propylene ~ Ketoprofen 20% 9 KET151 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 0.172 0.516 0 KET230 Propylene 7.0% 1,8- N Ketoprofen 20% 0K ET230 KET151 Ethanol glslyocporol pyl 30:70 Eucalyptus oil cineole Yes 8 3 1.418 4.254 -"10", 0' Ketoprofen 30% 1 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 0.5 1 0.038 0.114 """"'' KET230 lsopropyl w Ketoprofen 30% 2 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 1 0.04 0.12 0'I N KET230 lsopropyl Ul Ketoprofen 30% 3 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 4 1 0.09 0.27 KET230 lsopropyl Ketoprofen 30% 4 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 1 0.381 1.143 KET230 lsopropyl Ketoprofen 30% 5 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 1 1.379 4.137 KET230 lsopropyl Ketoprofen 30% 6 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 2 0.032 0.096 KET230 lsopropyl Ketoprofen 30% 7 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 2 2 0.05 0.15 en KET230 lsopropyl C Ketoprofen 30% 8 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 2 0.055 0.165 cr !!l. KET230 lsopropyl e Ketoprofen 30% 9 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 2 0.193 0.579 ~ ro KET231 lsopropyl 0 l.,J en Ketoprofen 30% 0 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 8 2 1.023 3.069 0 :;:,- "' (I) KET231 lsopropyl u, !2. 0.153= ...

Ketoprofen 30% 1 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 0.5 3 0.051 ""'' ;a KET231 lsopropyl .. "' C Ketoprofen 30% 2 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole No 2 3 0.072 0.216 0 1D "' KET231 lsopropyl 0 N I Ketoprofen 30% 3 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 4 3 0.18 0.54 0 ;0o) "' KET231 lsopropyl ,.I . 0 Ketoprofen 30% 4 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 6 3 1.263 3.789 ,.. ► KET231 lsopropyl C Ketoprofen 30% 5 KET152 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole No 8 3 4.731 14.193 KET231 lsopropyl Ketoprofen 30% 6 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 1 0.093 0.279 KET231 lsopropyl Ketoprofen 30% 7 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 1 1.385 4.155 KET231 lsopropyl Ketoprofen 30% 8 KET153 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 118-clneole Yes 4 1 7.738 23.214 KET231 lsopropyl Ketoprofen 30% 9 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 1 18.018 54.054 KET232 lsopropyl ""d Ketoprofen 30% 0 KET153 Ethanol myr!state 70:30 Eucalyptus oil 3.5% 118-clneole Yes 8 1 24.483 73.449 (") '"3 KET232 lsopropyl s;;: Ketoprofen 30% 1 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 0.5 2 0.712 2.136 KET232 lsopropyl ~ N Ketoprofen 30% 2 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 2 8.676 26.028 0 KET232 lsopropyl ""' QC) Ketoprofen 30% 3 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 2 17.707 53.121 -0 KET232 lsopropyl 0 Ketoprofen 30% 4 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 2 28.258 84.774 N KET232 lsopropyl Ul Ul Ketoprofen 30% 5 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 8 2 32.167 96.501 KET232 lsopropyl ~ Ketoprofen 30% 6 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 0.5 3 0.083 0.249 0 KET232 lsopropyl N Ketoprofen 30% 7K ET232 KET153 Ethanol lmsoyprirsotaptyel 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 2 3 0.632 1.896 -"10", 0' Ketoprofen 30% 8 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 4 3 4.565 13.695 ""' KET232 lsopropyl w""' Ketoprofen 30% 9 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 1,8-cineole Yes 6 3 11.565 34.695 0'I N KET233 lsopropyl Ul Ketoprofen 30% 0 KET153 Ethanol myristate 70:30 Eucalyptus oil 3.5% 118-cineole Yes 8 3 20.652 61.956 KET233 Propylene 7.0% 1,8- Ketoprofen 30% 1 KET154 Ethanol glycol 30:70 Eucalyptus oil cineole No 0.5 1 0.021 0.063 KET233 Propylene Ketoprofen 30% 2 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.03 0.09 KET233 Propylene Ketoprofen 30% 3 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 1 0.036 0.108 KET233 Propylene Ketoprofen 30% 4 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 0.026 O.Q78 en KET233 Propylene C Ketoprofen 30% 5 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 1 1.066 3.198 cr !!l. KET233 Propylene e Ketoprofen 30% 6 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.01 0.03 ~ ro KET233 Propylene 0 en Ketoprofen 30% 7 KET154 Ethanol glycol 30:70 Eucalyptus oil 7. 0% 1 "' 18-cineole No 2 2 0.008 0.024 0 :;:,- "' (I) KET233 Propylene u, !2. 0.177::: ...

Ketoprofen 30% 8 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 2 0.059 ""'' ;a KET233 Propylene Ul "' C Ketoprofen 30% 9 KET154 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-cineole No 6 2 0.13 0.39 0 1D "' KET234 Propylene 0 N I Ketoprofen 30% 0 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 1.574 4.722 0 ;0o) "' KET234 Propylene ,.I . 0 Ketoprofen 30% 1 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 O.Ql 0.03 ,.. ► KET234 Propylene C Ketoprofen 30% 2 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.017 0.051 KET234 Propylene Ketoprofen 30% 3 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 0.337 1.011 KET234 Propylene Ketoprofen 30% 4 KET154 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-dneole No 6 3 0.553 1.659 KET234 Propylene 7.0% 1,8- Ketoprofen 30% 5 KET154 Ethanol glycol 30:70 Eucalyptus oil cineole No 8 3 2.203 6.609 KET234 lsopropyl Ketoprofen 30% 6 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.193 0.579 KET234 lsopropyl ""d (") Ketoprofen 30% 7 KET155 Ethanol myr!state 30:70 Eucalyptus oil 7.0% 118-clneole No 2 1 5.319 15.957 '"3 KET234 lsopropyl s;;: Ketoprofen 30% 8 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 1 15.556 46.668 KET234 lsopropyl ~ N Ketoprofen 30% 9 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 1 29.995 89.985 0 KET235 lsopropyl "Q"C') Ketoprofen 30% 0 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 1 37.981 113.943 -0 KET235 lsopropyl 0 Ketoprofen 30% 1 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.069 0.207 N KET235 lsopropyl Ul Ul Ketoprofen 30% 2 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.563 1.689 KET235 lsopropyl ~ Ketoprofen 30% 3 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 2 2.736 8.208 0 KET235 lsopropyl N Ketoprofen 30% 4K ET235 KET155 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 7.0% 1,8-cineole No 6 2 9.287 27.861 -"10", 0' Ketoprofen 30% 5 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 2 16.473 49.419 ""' KET235 lsopropyl w""' Ketoprofen 30% 6 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.121 0.363 0'I N KET235 lsopropyl Ul Ketoprofen 30% 7 KET155 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 2 3 0.262 0.786 KET235 lsopropyl Ketoprofen 30% 8 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 4 3 1.626 4.878 KET235 lsopropyl Ketoprofen 30% 9 KET155 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole No 6 3 6.184 18.552 KET236 lsopropyl Ketoprofen 30% 0 KET155 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole No 8 3 13.16 39.48 KET236 Propylene 7.0% 1,8- Ketoprofen 30% 1 KET156 Ethanol glycol 30:70 Eucalyptus oil cineole Yes 0.5 1 0.01 0.03 en KET236 Propylene C Ketoprofen 30% 2 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.012 0.036 cr !!l. KET236 Propylene e Ketoprofen 30% 3 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 0.126 0.378 ~ ro KET236 Propylene 0 en Ketoprofen 30% 4 KET156 Ethanol glycol 30:70 Eucalyptus oil 7. 0% 1 "' 18-cineole Yes 6 1 0.178 0.534 0 :;:,- "' (I) KET236 Propylene u, !2. 1.686= ...

Ketoprofen 30% 5 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 0.562 ""'' ;a KET236 Propylene 0'I "' C Ketoprofen 30% 6 KET156 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 0.5 2 0.02 0.06 0 1D "' KET236 Propylene 0 N I Ketoprofen 30% 7 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.014 0.042 0 ;0o) "' KET236 Propylene ,.I . 0 Ketoprofen 30% 8 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 0.057 0.171 ,.. ► KET236 Propylene C Ketoprofen 30% 9 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 0.213 0.639 KET237 Propylene Ketoprofen 30% 0 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 0.766 2.298 KET237 Propylene Ketoprofen 30% 1 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-dneole Yes 0.5 3 O.Ql 0.03 KET237 Propylene Ketoprofen 30% 2 KET156 Ethanol glycol 30:70 Eucalyptus oil 7 .0% 118-clneole Yes 2 3 0.01 0.03 KET237 Propylene Ketoprofen 30% 3 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.029 0.087 KET237 Propylene ""d Ketoprofen 30% 4 KET156 Ethanol glycol 30:70 Eucalyptus oil 7.0% 118-clneole Yes 6 3 0.046 0.138 (") '"3 KET237 Propylene 7.0% 1,8- s;;: Ketoprofen 30% 5 KET156 Ethanol glycol 30:70 Eucalyptus oil cineole Yes 8 3 0.653 1.959 KET237 lsopropyl ~ N Ketoprofen 10% 6 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.062 0.186 0 KET237 lsopropyl "Q"C') Ketoprofen 10% 7 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.105 0.315 -0 KET237 lsopropyl 0 Ketoprofen 10% 8 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 1.085 3.255 N KET237 lsopropyl Ul Ul Ketoprofen 10% 9 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.199 0.597 KET238 lsopropyl ~ Ketoprofen 10% 0 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 0.378 1.134 0 KET238 lsopropyl N Ketoprofen 10% 1K ET238 KET157 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.079 0.237 -"10", 0' Ketoprofen 10% 2 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.572 1.716 ""' KET238 lsopropyl w""' Ketoprofen 10% 3 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 0.521 1.563 0'I N KET238 lsopropyl Ul Ketoprofen 10% 4 KET157 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 6 2 3.888 11.664 KET238 lsopropyl Ketoprofen 10% 5 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 4.691 14.073 KET238 lsopropyl Ketoprofen 10% 6 KET157 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 0.5 3 0.062 0.186 KET238 lsopropyl Ketoprofen 10% 7 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 3 0.539 1.617 KET238 lsopropyl Ketoprofen 10% 8 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.085 0.255 en KET238 lsopropyl C Ketoprofen 10% 9 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 3.897 11.691 cr !!l. KET239 lsopropyl e Ketoprofen 10% 0 KET157 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 3 5.128 15.384 ~ ro KET239 Propylene 7.0% 1,8- 0 en Ketoprofen 10% 1 KET158 Ethanol glycol 50:50 Eucalyptus oil cineole No 0.5 1 0.008 0.024 "0 ' :;:,- "' (I) KET239 Propylene u, !2. 0.057= ...

Ketoprofen 10% 2 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.019 ""'' ;a KET239 Propylene -.,l "' C Ketoprofen 10% 3 KET158 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole No 4 1 0.057 0.171 0 1D "' KET239 Propylene 0 N I Ketoprofen 10% 4 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 0.02 0.05 0 ;0o) "' KET239 Propylene ,.I . 0 Ketoprofen 10% 5 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 1 0.09 0.27 ,.. ► KET239 Propylene C Ketoprofen 10% 5 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.012 0.035 KET239 Propylene Ketoprofen 10% 7 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.012 0.036 KET239 Propylene Ketoprofen 10% 8 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-dneole No 4 2 0.211 0.533 KET239 Propylene Ketoprofen 10% 9 KET158 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-clneole No 6 2 0.604 1.812 KET240 Propylene Ketoprofen 10% 0 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 1.757 5.271 KET240 Propylene ""d Ketoprofen 10% 1 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 118-clneole No 0.5 3 0.014 0.042 (") '"3 KET240 Propylene s;;: Ketoprofen 10% 2 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 118-cineole No 2 3 0.203 0.609 KET240 Propylene ~ N Ketoprofen 10% 3 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 4.025 12.075 0 KET240 Propylene ""' QC) Ketoprofen 10% 4 KET158 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 3 4.648 13.944 -0 KET240 Propylene 7.0% 1,8- 0 Ketoprofen 10% 5 KET158 Ethanol glycol 50:50 Eucalyptus oil cineole No 8 3 19.304 57.912 N KET240 lsopropyl Ul Ul Ketoprofen 10% 6 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.07 0.21 KET240 lsopropyl ~ Ketoprofen 10% 7 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.42 1.26 0 KET240 lsopropyl N Ketoprofen 10% 8K ET240 KET159 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 1 0.189 0.567 -"10", 0' Ketoprofen 10% 9 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 2.76 8.28 ""' KET241 lsopropyl w""' Ketoprofen 10% 0 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 1 3.769 11.307 0'I N KET241 lsopropyl Ul Ketoprofen 10% 1 KET159 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole No 0.5 2 0.06 0.18 KET241 lsopropyl Ketoprofen 10% 2 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.484 1.452 KET241 lsopropyl Ketoprofen 10% 3 KET159 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole No 4 2 7.984 23.952 KET241 lsopropyl Ketoprofen 10% 4 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 2 3.159 9.477 KET241 lsopropyl Ketoprofen 10% 5 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 4.48 13.44 en KET241 lsopropyl C Ketoprofen 10% 6 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.059 0.177 cr !!l. KET241 lsopropyl e Ketoprofen 10% 7 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.124 0.372 ~ ro KET241 lsopropyl 0 en Ketoprofen 10% 8 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 4.989 14.967 "0 ' :;:,- lsopropyl "' (I) KET241 u, 2.607= ... !2.

Ketoprofen 10% 9 KET159 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 3 0.869 ""'' ;a KET242 lsopropyl QC) "' C Ketoprofen 10% 0 KET159 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole No 8 3 3.86 11.58 0 1D "' KET242 Propylene 7.0% 1,8- 0 N I Ketoprofen 10% 1 KET160 Ethanol glycol 50:50 Eucalyptus oil cineole Yes 0.5 1 0.015 0.045 0 ;0o) "' KET242 Propylene ,.I . 0 Ketoprofen 10% 2 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.017 0.051 ,.. ► KET242 Propylene C Ketoprofen 10% 3 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 0.297 0.891 KET242 Propylene Ketoprofen 10% 4 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.583 1.749 KET242 Propylene Ketoprofen 10% 5 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-dneole Yes 8 1 3.951 11.853 KET242 Propylene Ketoprofen 10% 6 KET160 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-clneole Yes 0.5 2 0.011 0.033 KET242 Propylene Ketoprofen 10% 7 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.008 0.024 KET242 Propylene ""d Ketoprofen 10% 8 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 118-clneole Yes 4 2 0.012 0.036 (") '"3 KET242 Propylene s;;: Ketoprofen 10% 9 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 118-cineole Yes 6 2 0.064 0.192 KET243 Propylene ~ N Ketoprofen 10% 0 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 0.484 1.452 0 KET243 Propylene ""' QC) Ketoprofen 10% 1 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.012 0.036 -0 KET243 Propylene 0 Ketoprofen 10% 2 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 3 0.012 0.036 N KET243 Propylene Ul Ul Ketoprofen 10% 3 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.246 0.738 KET243 Propylene ~ Ketoprofen 10% 4 KET160 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 0.271 0.813 0 KET243 Propylene 7.0% 1,8- N Ketoprofen 10% 5K ET243 KET160 Ethanol glslyocporol pyl 50:50 Eucalyptus oil cineole Yes 8 3 2.103 6.309 -1"0", 0' Ketoprofen 10% 6 KET161 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 0.5 1 0.094 0.282 """"'' KET243 lsopropyl w Ketoprofen 10% 7 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.767 2.301 0'I N KET243 lsopropyl Ul Ketoprofen 10% 8 KET161 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 4 1 1.838 5.514 KET243 lsopropyl Ketoprofen 10% 9 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.652 1.956 KET244 lsopropyl Ketoprofen 10% 0 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 1.516 4.548 KET244 lsopropyl Ketoprofen 10% 1 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.051 0.153 KET244 lsopropyl Ketoprofen 10% 2 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.242 0.726 en KET244 lsopropyl C Ketoprofen 10% 3 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 1.415 4.245 cr !!l. KET244 lsopropyl e Ketoprofen 10% 4 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 3.33 9.99 ~ ro KET244 lsopropyl 0 l.,J en Ketoprofen 10% 5 KET161 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 8 2 4.133 12.399 0 :;:,- "' (I) KET244 lsopropyl u, !2. 0.192::: ...

Ketoprofen 10% 6 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.064 ""'' ;a KET244 lsopropyl 1,0 "' C Ketoprofen 10% 7 KET161 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 2 3 0.264 0.792 0 1D "' KET244 lsopropyl 0 N I Ketoprofen 10% 8 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 5.348 16.044 0 ;0o) "' KET244 lsopropyl ,.I . 0 Ketoprofen 10% 9 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 4.038 12.114 ,.. ► KET245 lsopropyl C Ketoprofen 10% 0 KET161 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 3 1.22 3.66 KET245 lsopropyl Ketoprofen 20% 1 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.117 0.351 KET245 lsopropyl Ketoprofen 20% 2 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-dneole Yes 2 1 0.106 0.318 KET245 lsopropyl Ketoprofen 20% 3 KET162 Ethanol myr!state 30:70 Eucalyptus oil 7 .0% 118-clneole Yes 4 1 0.204 0.612 KET245 lsopropyl Ketoprofen 20% 4 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.852 2.556 KET245 lsopropyl ""d Ketoprofen 20% 5 KET162 Ethanol myr!state 30:70 Eucalyptus oil 7.0% 118-clneole Yes 8 1 1.787 5.361 (") '"3 KET245 lsopropyl s;;: Ketoprofen 20% 6 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 118-cineole Yes 0.5 2 0.087 0.261 KET245 lsopropyl ~ N Ketoprofen 20% 7 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 1.066 3.198 0 KET245 lsopropyl ""' QC) Ketoprofen 20% 8 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 6.232 18.696 -0 KET245 lsopropyl 0 Ketoprofen 20% 9 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 15.057 45.171 N KET246 lsopropyl Ul Ul Ketoprofen 20% 0 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 18.571 55.713 KET246 lsopropyl ~ Ketoprofen 20% 1 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.09 0.27 0 KET246 lsopropyl N Ketoprofen 20% K2E T246 KET162 Ethanol lmsoyprirsotaptyel 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 3 0.324 0.972 -"10", 0' Ketoprofen 20% 3 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 2.459 7.377 ""' KET246 lsopropyl w""' Ketoprofen 20% 4 KET162 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 7.619 22.857 0'I N KET246 lsopropyl Ul Ketoprofen 20% 5 KET162 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 8 3 10.657 31.971 KET246 Propylene 7.0% 1,8- Ketoprofen 20% 6 KET163 Ethanol glycol 50:50 Eucalyptus oil cineole No 0.5 1 0.01 0.03 KET246 Propylene Ketoprofen 20% 7 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.154 0.462 KET246 Propylene Ketoprofen 20% 8 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 1 3.099 9.297 KET246 Propylene Ketoprofen 20% 9 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 8.957 26.871 en KET247 Propylene C Ketoprofen 20% 0 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 1 23.383 70.149 cr !!l. KET247 Propylene e Ketoprofen 20% 1 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.007 0.021 ~ ro KET247 Propylene 0 en Ketoprofen 20% 2 KET163 Ethanol glycol 50:50 Eucalyptus oil 7. 0% 1 "' 18-cineole No 2 2 0.035 0.105 0 :;:,- "' (I) KET247 Propylene u, !2. 8.226~ ...

Ketoprofen 20% 3 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 2 2.742 ""'' ;a KET247 Propylene 0 "' C Ketoprofen 20% 4 KET163 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole No 6 2 3.286 9.858 0 1D "' KET247 Propylene 0 N I Ketoprofen 20% 5 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 15.666 46.998 0 ;0o) "' KET247 Propylene ,.I . 0 Ketoprofen 20% 6 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.007 0.021 ,.. ► KET247 Propylene C Ketoprofen 20% 7 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.01 0.03 KET247 Propylene Ketoprofen 20% 8 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 0.183 0.549 KET247 Propylene Ketoprofen 20% 9 KET163 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-dneole No 6 3 0.469 1.407 KET248 Propylene 7.0% 1,8- Ketoprofen 20% 0 KET163 Ethanol glycol 50:50 Eucalyptus oil cineole No 8 3 1.298 3.894 KET248 lsopropyl Ketoprofen 20% 1 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.047 0.141 KET248 lsopropyl ""d (") Ketoprofen 20% 2 KET164 Ethanol myr!state 50:50 Eucalyptus oil 7.0% 118-clneole No 2 1 0.234 0.702 '"3 KET248 lsopropyl s;;: Ketoprofen 20% 3 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 1 1.212 3.636 KET248 lsopropyl ~ N Ketoprofen 20% 4 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 3.845 11.535 0 KET248 lsopropyl "Q"C') Ketoprofen 20% 5 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 1 6.208 18.624 -0 KET248 lsopropyl 0 Ketoprofen 20% 6 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 2 0.056 0.168 N KET248 lsopropyl Ul Ul Ketoprofen 20% 7 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.228 0.684 KET248 lsopropyl ~ Ketoprofen 20% 8 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 2 3.9 11.7 0 KET248 lsopropyl N Ketoprofen 20% 9K ET249 KET164 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 2 3.446 10.338 -"10", 0' Ketoprofen 20% 0 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 6.828 20.484 ""' KET249 lsopropyl w""' Ketoprofen 20% 1 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.112 0.336 0'I N KET249 lsopropyl Ul Ketoprofen 20% 2 KET164 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole No 2 3 1.762 5.286 KET249 lsopropyl Ketoprofen 20% 3 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 1.296 3.888 KET249 lsopropyl Ketoprofen 20% 4 KET164 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole No 6 3 9.296 27.888 KET249 lsopropyl Ketoprofen 20% 5 KET164 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 3 16.225 48.675 KET249 Propylene 7.0% 1,8- Ketoprofen 20% 6 KET165 Ethanol glycol 50:50 Eucalyptus oil cineole Yes 0.5 1 0.016 0.048 en KET249 Propylene C Ketoprofen 20% 7 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.015 0.045 cr !!l. KET249 Propylene e Ketoprofen 20% 8 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 0.147 0.441 ~ ro KET249 Propylene 0 en Ketoprofen 20% 9 KET165 Ethanol glycol 50:50 Eucalyptus oil 7. 0% 1 "' 18-cineole Yes 6 1 0.45 1.35 0 :;:,- "' (I) KET250 Propylene u, !2. 7.671~ ...

Ketoprofen 20% 0 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 2.557 ""'' ;a KET250 Propylene ""' "' C Ketoprofen 20% 1 KET165 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 0.5 2 0.008 0.024 0 1D "' KET250 Propylene 0 N I Ketoprofen 20% 2 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.014 0.042 0 ;0o) "' KET250 Propylene ,.I . 0 Ketoprofen 20% 3 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 0.147 0.441 ,.. ► KET250 Propylene C Ketoprofen 20% 4 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 0.185 0.555 KET250 Propylene Ketoprofen 20% 5 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 0.525 1.575 KET250 Propylene Ketoprofen 20% 6 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-dneole Yes 0.5 3 0.013 0.039 KET250 Propylene Ketoprofen 20% 7 KET165 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-clneole Yes 2 3 0.007 0.021 KET250 Propylene Ketoprofen 20% 8 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 0.331 0.993 KET250 Propylene ""d Ketoprofen 20% 9 KET165 Ethanol glycol 50:50 Eucalyptus oil 7.0% 118-clneole Yes 6 3 0.573 1.719 (") '"3 KET251 Propylene 7.0% 1,8- s;;: Ketoprofen 20% 0 KET165 Ethanol glycol 50:50 Eucalyptus oil cineole Yes 8 3 1.374 4.122 KET251 lsopropyl ~ N Ketoprofen 20% 1 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.085 0.255 0 KET251 lsopropyl "Q"C') Ketoprofen 20% 2 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.986 2.958 -0 KET251 lsopropyl 0 Ketoprofen 20% 3 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 1 4.006 12.018 N KET251 lsopropyl Ul Ul Ketoprofen 20% 4 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 8.567 25.701 KET251 lsopropyl ~ Ketoprofen 20% 5 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 15.529 46.587 0 KET251 lsopropyl N Ketoprofen 20% 6K ET251 KET166 Ethanol lmsoyprirsotaptyel 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.112 0.336 -"10", 0' Ketoprofen 20% 7 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 2.146 6.438 ""' KET251 lsopropyl w""' Ketoprofen 20% 8 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 9.022 27.066 0'I N KET251 lsopropyl Ul Ketoprofen 20% 9 KET166 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 6 2 15.756 47.268 KET252 lsopropyl Ketoprofen 20% 0 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 20.915 62.745 KET252 lsopropyl Ketoprofen 20% 1 KET166 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 0.5 3 0.045 0.135 KET252 lsopropyl Ketoprofen 20% 2 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 3 0.876 2.628 KET252 lsopropyl Ketoprofen 20% 3 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 4.699 14.097 en KET252 lsopropyl C Ketoprofen 20% 4 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 8.932 26.796 cr !!l. KET252 lsopropyl e Ketoprofen 20% 5 KET166 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 3 13.891 41.673 ~ ro KET252 lsopropyl 0 en Ketoprofen 30% 6 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.111 0.333 "0 ' :;:,- lsopropyl "' (I) KET252 u, 0.522~ ... !2.

Ketoprofen 30% 7 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0.174 ""'' ;a KET252 lsopropyl N "' C Ketoprofen 30% 8 KET167 Ethanol myristate 30:70 Eucalyptus oil 7 .0% 118-cineole Yes 4 1 2.104 6.312 0 1D "' KET252 lsopropyl 0 N I Ketoprofen 30% 9 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 6.267 18.801 0 ;0o) "' KET253 lsopropyl ,.I . 0 Ketoprofen 30% 0 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 12.945 38.835 ,.. ► KET253 lsopropyl C Ketoprofen 30% 1 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.112 0.336 KET253 lsopropyl Ketoprofen 30% 2 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.397 1.191 KET253 lsopropyl Ketoprofen 30% 3 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 4.412 13.236 KET253 lsopropyl Ketoprofen 30% 4 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 10.328 30.984 KET253 lsopropyl Ketoprofen 30% 5 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 18.162 54.486 KET253 lsopropyl ""d Ketoprofen 30% 6 KET167 Ethanol myr!state 30:70 Eucalyptus oil 7.0% 1,8-clneole Yes 0.5 3 0.083 0.249 (") '"3 KET253 lsopropyl s;;: Ketoprofen 30% 7 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 118-cineole Yes 2 3 1.142 3.426 KET253 lsopropyl ~ N Ketoprofen 30% 8 KET167 Ethanol myr!state 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 8.465 25.395 0 KET253 lsopropyl ""' QC) Ketoprofen 30% 9 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 12.84 38.52 -0 KET254 lsopropyl 0 Ketoprofen 30% 0 KET167 Ethanol myristate 30:70 Eucalyptus oil 7.0% 1,8-cineole Yes 8 3 19.458 58.374 0 N KET254 Propylene 7.0% 1,8- Ul Ul Ketoprofen 30% 1 KET168 Ethanol glycol 50:50 Eucalyptus oil cineole No 0.5 1 5.977 17.931 KET254 Propylene ~ Ketoprofen 30% 2 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 1 7.033 21.099 0 KET254 Propylene N Ketoprofen 30% 3K ET254 KET168 Ethanol gPlryocpoyl lene 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 1 7.901 23.703 -1"0", 0' Ketoprofen 30% 4 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 12.529 37.587 ""' KET254 Propylene w""' Ketoprofen 30% 5 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 1 20.847 62.541 0'I N KET254 Propylene Ul Ketoprofen 30% 6 KET168 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole No 0.5 2 0.499 1.497 KET254 Propylene Ketoprofen 30% 7 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 2 0.661 1.983 KET254 Propylene Ketoprofen 30% 8 KET168 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole No 4 2 1.092 3.276 KET254 Propylene Ketoprofen 30% 9 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 2 1.361 4.083 KET255 Propylene Ketoprofen 30% 0 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 1.431 4.293 en KET255 Propylene C Ketoprofen 30% 1 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.118 0.354 cr !!l. KET255 Propylene e Ketoprofen 30% 2 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.269 0.807 ~ ro KET255 Propylene 0 en Ketoprofen 30% 3 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 3.847 11.541 "0 ' :;:,- Propylene "' (I) KET255 u, 10.455 ~ ... !2.

Ketoprofen 30% 4 KET168 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 3 3.485 ""'' ;a KET255 Propylene 7.0% 1,8- w "' C Ketoprofen 30% 5 KET168 Ethanol glycol 50:50 Eucalyptus oil cineole No 8 3 5.79 17.37 0 1D "' KET255 lsopropyl 0 N I Ketoprofen 30% 6 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 1 0.095 0.285 0 ;0o) "' KET255 lsopropyl ,.I . 0 Ketoprofen 30% 7 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 1 0.168 0.504 ,.. ► KET255 lsopropyl C Ketoprofen 30% 8 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 1 2.63 7.89 KET255 lsopropyl Ketoprofen 30% 9 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 1 7.315 21.945 KET256 lsopropyl Ketoprofen 30% 0 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-dneole No 8 1 14.825 44.475 KET256 lsopropyl Ketoprofen 30% 1 KET169 Ethanol myr!state 50:50 Eucalyptus oil 7 .0% 118-clneole No 0.5 2 0.056 0.168 KET256 lsopropyl Ketoprofen 30% 2 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 2 1.259 3.777 KET256 lsopropyl ""d Ketoprofen 30% 3 KET169 Ethanol myr!state 50:50 Eucalyptus oil 7.0% 118-clneole No 4 2 7.345 22.035 (") '"3 KET256 lsopropyl s;;: Ketoprofen 30% 4 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 118-cineole No 6 2 16.244 48.732 KET256 lsopropyl ~ N Ketoprofen 30% 5 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 8 2 25.968 77.904 0 KET256 lsopropyl ""' QC) Ketoprofen 30% 6 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 0.5 3 0.04 0.12 -0 KET256 lsopropyl 0 Ketoprofen 30% 7 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 2 3 0.529 1.587 N KET256 lsopropyl Ul Ul Ketoprofen 30% 8 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 4 3 4.881 14.643 KET256 lsopropyl ~ Ketoprofen 30% 9 KET169 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole No 6 3 12.469 37.407 0 KET257 lsopropyl N Ketoprofen 30% 0 KET169 KET257 Ethanol Pmryorpisytlaentee 50:50 Eucalyptus oil 77..00%% 11,,88--cineole No 8 3 22.167 66.501 -"10", 0' Ketoprofen 30% 1 KET170 Ethanol glycol 50:50 Eucalyptus oil cineole Yes 0.5 1 0.027 0.081 """"'' KET257 Propylene w Ketoprofen 30% 2 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 1 0 0 0'I N KET257 Propylene Ul Ketoprofen 30% 3 KET170 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 4 1 0.1 0.3 KET257 Propylene Ketoprofen 30% 4 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 0.238 0.714 KET257 Propylene Ketoprofen 30% 5 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 1 0.899 2.697 KET257 Propylene Ketoprofen 30% 6 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.034 0.102 KET257 Propylene Ketoprofen 30% 7 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 0.029 0.087 en KET257 Propylene C Ketoprofen 30% 8 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 0.121 0.363 cr !!l. KET257 Propylene e Ketoprofen 30% 9 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 0.172 0.516 ~ ro KET258 Propylene 0 l.,J en Ketoprofen 30% 0 KET170 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 8 2 0.42 1.26 0 :;:,- "' (I) KET258 Propylene u, !2. 1.362 ~ ...

Ketoprofen 30% 1 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 3 0.454 ""'' ;a KET258 Propylene .. "' C Ketoprofen 30% 2 KET170 Ethanol glycol 50:50 Eucalyptus oil 7 .0% 118-cineole Yes 2 3 0.421 1.263 0 1D "' KET258 Propylene 0 N I Ketoprofen 30% 3 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 3 5.979 17.937 0 ;0o) "' KET258 Propylene ,.I . 0 Ketoprofen 30% 4 KET170 Ethanol glycol 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 3 5.739 17.217 ,.. ► KET258 Propylene 7.0% 1,8- C Ketoprofen 30% 5 KET170 Ethanol glycol 50:50 Eucalyptus oil cineole Yes 8 3 8.202 24.606 KET258 lsopropyl Ketoprofen 30% 6 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 1 0.644 1.932 KET258 lsopropyl Ketoprofen 30% 7 KET171 Ethanol myristate 50:50 Eucalyptus oil 7 .0% 1,8-cineole Yes 2 1 6.599 19.797 KET258 lsopropyl Ketoprofen 30% 8 KET171 Ethanol myr!state 50:50 Eucalyptus oil 7 .0% 1,8-clneole Yes 4 1 21.617 64.851 KET258 lsopropyl Ketoprofen 30% 9 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 1 30.099 90.297 KET259 lsopropyl ""d (") Ketoprofen 30% 0 KET171 Ethanol myr!state 50:50 Eucalyptus oil 7.0% 1,8-clneole Yes 8 1 35.084 105.252 '"3 KET259 lsopropyl s;;: Ketoprofen 30% 1 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 0.5 2 0.231 0.693 KET259 lsopropyl ~ N Ketoprofen 30% 2 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 2 2 3.496 10.488 0 KET259 lsopropyl "Q"C') Ketoprofen 30% 3 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 4 2 12.012 36.036 -0 KET259 lsopropyl 0 Ketoprofen 30% 4 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 6 2 16.294 48.882 N KET259 lsopropyl Ul Ul Ketoprofen 30% 5 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes 8 2 20.867 62.601 KET259 lsopropyl Ketoprofen 30% 6 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes KET259 lsopropyl Ketoprofen 30% 7 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes KET259 lsopropyl Ketoprofen 30% 8 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes KET259 lsopropyl Ketoprofen 30% 9 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes KET260 lsopropyl Ketoprofen 30% 0 KET171 Ethanol myristate 50:50 Eucalyptus oil 7.0% 1,8-cineole Yes (/) C: cr ~ e ro (/) ::, Cl) ~ ;o C: 1D N O'.> ;\J ► C 0.5 3 0.659 2 3 6.032 4 3 16.236 6 3 20.343 8 3 24.634 1.977 18.096 48.708 61.029 73.902 ... N Ul ~ N .0. . -..\..0.. w 0'I N Ul "l:j (") ""'3 ~ ~ N .0. . ~ 0 N Ul Ul ~ 0 "' 0 ."".'' ""'' "' 0 "' 0 I 0 "' ,,..I ..

WO 2019/113625 - 126 - PCT/AU2018/000255 Discussion To confirm transdermal penetration of candidate formulations using in vitro techniques Regional differences in transdermal drug penetration This study has shown that there are significant differences in the penetration of lignocaine hydrochloride through different regions of cattle skin in vitro.

Regional differences in transdermal drug penetration has also been reported in cats (Hill et al., 2015), horses 10 (Mills and Cross, 2006b, 2007a, b) and dogs (Mills et al., 2004b, a, 2005).

However, the specific differences between regions will depend on both the active drug and the vehicle used.

In the current study, lignocaine hydrochloride was dissolved in an alcohol-based vehicle containing a surfactant, which was associated with a significantly higher penetration of active drug through skin harvested from the thorax and scrotal regions.

Specific reasons for the regional differences are uncertain, although the scrotal skin was observed to be grossly thinner with finer hair present on the skin, compared to the skin from dorsal midline, thorax and ventral abdomen.

Regional differences may relate to the thickness of the stratum corneum (Monteiro-Riviere et al., 1990), regional cutaneous 20 blood flow (Monteiro-Riviere et al., 1990), the size of corneocytes (Kashibuchi et al., 2002; McEwan et al., 2009) and density of hair fo11icles (Damodaram and Seshadri, 1984; Steelman et al., 1997).

Since the current study used in vitro diffusion cells, cutaneous blood flow did not contribute to the outcomes, although it is generally higher in the ventral abdomen compared to the buttocks, ear and shoulder and dorsal midline 25 (Monteiro-Riviere et al., 1990).

In contrast, the epidermis thickness in the skin from ventral abdomen is generally lower than other regions.

However, the primary barrier to WO 2019/113625 - 127 - PCT/AU2018/000255 drug penetration is the stratum corneum and can be directly evaluated using diffusion cells in vitro (Mills and Cross, 2006).

The selection of the four regions used in the current study was based on potential sites 5 where topical drug may be applied to cattle.

The scrotal skin is incised during castration and an effective local anaesthetic would significantly reduce pain associated with this procedure, yet could be applied by lay operators.

Topical drugs are usually applied to the thorax or dorsal midline for convenience, but this also facilitates larger volumes of formulation to be applied, if required, for adequate systemic effects.

Moreover, many 10 pour-on drugs applied along the dorsal midline will tend to run ventrally over the thorax.

The abdomen was included in this study since studies in other species have demonstrated that some drugs will penetrate through the abdomen and/or groin region to a greater extent than other regions (Mills et al., 2004a, b; Mills and Cross, 2006b, 2007a, b).

However, the current study showed that the thorax was more permeable to the specific formulation 15 used, although lignocaine hydrochloride also penetrated through the other regions tested.

Screening of NSAID and vehicle combinations to maximise active drug penetration through cattle skin Of the four NSAIDs currently registered for use in cattle in Australia, only ketoprofen and 20 flunixin meglumine actually penetrated through skin in the vehicles tested.

Tolfenamic acid was poorly soluble in almost every vehicle tested, while meloxicam had poor percutaneous penetration.

It was therefore decided to move forward with ketoprofen since it penetrated through bovine skin significantly higher, in terms of rate and extent, than flunixin meglumine.

The combination with eucalyptus oil was interesting, since a 25 number of the commercially-available vehicles (from Croda) had a basis in eucalyptol, WO 2019/113625 - 128 - PCT/AU2018/000255 while the terpenes were generally useful vehicle excipients to enhance drug movement through the skin.

Optimising the candidate formulations 5 The final formulation was determined based of a number of factors.

It was considered advisable that isopropanol would be preferable in any topical preparation due to its low flammability.

Occupational health and Safety were a consideration when spraying a potentially flammable mixture on cattle.

However, isopropanol did not enhance active drug movement as well as ethanol, so the latter was retained.

Similarly, 1PM was selected 10 as a solubilising agent, proving superior to other potential agents, including propylene glycol and oleyl alcohol.

The 50:50 combination of ethanol and IPM maximally enhanced the movement of ketoprofen through cattle skin, supported by I 0% eucalyptus oil. 15 The amount of active drug required in the formulation was unknown.

Other commercial formulations containing NSIDs for human topical application contain 10+% of active drug.

Up to 30% ketoprofen could be dissolved in the final vehicle formulation, although some precipitation occurred, while 20% dissolved easily without precipitation.

Since it was uncertain how much drug would actually get through cattle skin in vivo, it was 20 decided to incorporate 20% active into the final formulation.

This would also minimise the volume of formulation that needed to be applied.

Stability studies of the final formulation The stability study was intended as a preliminary assessment to provide some support for 25 the final formulation if advanced to production.

The environmental conditions used (0, 20 WO 2019/113625 - 129 - PCT/AU2018/000255 and 40 °C) approximated potential storage or use conditions in the field.

Despite a mild colour change after several months at 40 °C, the concentration of active drug remained stable (20 ± 1 %).

It was concluded that the formulation was quite stable under a range of conditions and storage.

Analysis of ketoprofen in biological samples The analytical methodology was reliable and consistent, with a low and appropriate limit of detection.

The use of mass spectrometry ensured that parent drug was detected and any metabolites identified.

Summary To determine the efficacy of candidate transdermal formulations to control pain associated with surgical husbandry formulations Pilot study 1 and 2 Despite the in vitro data, it was uncertain how much active drug would reach the systemic circulation and how quickly.

In vitro studies using Franz cells are widely acknowledged as useful for proof-of-concept studies and to screen large numbers of potential drug and 20 vehicle combinations.

However, other factors must be considered when applying formulations to the living animal, including metabolism in the skin (both phase 1 and phase 2 metabolism occurs), the effects of cutaneous blood flow and the potential of the active to move away for the dermis and enter the systemic circulation (Mills and Cross, 2006a).

Significant concentrations of ketoprofen were detected systemically in plasma 25 following transdermal application of the novel formulation.

The 40 mL dose resulted in WO 2019/113625 - 130 - PCT/AU2018/000255 obvious precipitation of the skin of the calves and resulted in peak ( CMAx) concentrations of up to 43 μg/mL in the plasma, with drug appearing within 30 min (this was the first blood collection time) and peaking at ~2 hr.

This was much faster than expected.

The study was repeated with only the 10 mL dose, which resulted in a CMAX of 3-10 μg/mL, 5 again around 2 hr, within initial drug appearing in the plasma after ~ 30 min.

These concentrations approached what had been reported following IM administration (3 mg/kg) and, as such, could be considered therapeutic (see Plessers et al 2015).

No adverse effects were observed in the cattle. 10 Bioavailability study This was a major study to determine the bioavailability of ketoprofen from the transdermal formulation and to compare the pharmacokinetics with IM administration.

The use of a cross-over study with animals in the target age group (i.e. when dehorning is normally undertaken) added power and relevance to the study design.

The bioavailability of ketoprofen was ~ 50%, which is a good outcome for a topicallyadministered drug.

More importantly, the lag phase (the time between application and first appearance in the plasma) was exceptionally short for the transdermal route, with drug appearing within 10-15 min.

Furthermore, the CMAX and AUC were almost twice that 20 measured after IM administration, although the T'MAX for IM (74 min) was faster than transdermal delivery ( 115 min).

These pharmacokinetic findings suggest that the transdermal route is a rapid and effective route to deliver ketoprofen to calves.

Further mode11ing and dose administration should be undertaken, but a sma11er dose rate (i.e. volume) of the transdermal formulation could be applied to achieve a similar efficacy 25 (determined by CMAX and AUC) as IM administration.

Moreover, reducing the volume of WO 2019/113625 - 131 - PCT/AU2018/000255 drug applied could also reduce the TMAX, meaning that the transdermal formulation could have a similar pharmacokinetic profile as IM administration.

The skin irritation and excoriation noted in the bioavailability study was a concern and 5 had not been observed in the calves in the pilot studies or the clinical study.

It should be noted, however, that the formulation had not been washed off in the other studies.

The exact cause of this irritation is uncertain, although ketoprofen is a known photosensitising agent (Guy, et al., 2014; Seto et al., 2015).

Since the active drug was absorbed so rapidly following topical administration, less of the active drug should have remained on the skin.

To develop a formulation containing an NSAID to control pain associated with routine surgical interventions for up to 24 hr Clinical study 15 This study was performed on calves at an age when they would normally be dehorned. A cornual nerve block was not used (this was approved by the animal ethics committee) since this represents the industry standard currently. A sham-handled group was used as a negative control to allow for the stress induced by handling and multiple blood samples collected.

The remaining calves were all dehorned and no adverse effects were observed.

An important consideration for the clinical study was that the bioavailability study had already demonstrated that the transdermal formulation resulted in a higher systemic concentration of ketoprofen than the IM administration and, while slower in onset, persisted in the plasma for longer.

These findings suggested that the efficacy of the 25 transdermal formulation would be similar, if not better than, IM ketoprofen, from a WO 2019/113625 - 132 - PCT/AU2018/000255 bioequivalence perspective.

The literature has already shown that IM ketoprofen has an analgesic effect lasting at least 24 hr in cattle following surgical husbandry procedures.

Conventional parameters to assessment pain and inflammation 5 All the conventional parameters indicated that ketoprofen had a significant analgesic effect in the cattle.

Total plasma cortisol and body weight gain were significantly different between treated and untreated calves, but there were no significant difference between the routes of administration of the ketoprofen.

Dehorned calves that received ketoprofen had a body weight gain that was similar to the sham-treated cattle and 10 significantly higher than the placebo-treated cattle.

These findings indicated that transdermal ketoprofen had a similar or higher efficacy than IM ketoprofen and this significantly reduced pain and stress in cattle fo11owing dehorning.

Proteomic assessment of pain and inflammation 15 Unfortunately, the analysis of the proteomic data was continuing while this report was being combined.

Over 300 proteins had been isolated and identified, consisting of two or more peptides each.

The software packages to automatically identify the proteins proved inaccurate and much of the spectral library was confirmed manually.

Irrespective, some important trends were emerging, backing up the conventional parameters.

The response to 20 dehorning (Figure 19b) was substantially different from sham.

There was a difference between untreated and treated cattle, meaning that ketoprofen significantly affected key biomarkers of pain and inflammation, while the transdermal ketoprofen appeared to have greater efficacy than IM delivery. 25 Conclusions/recommendations WO 2019/113625 - 133 - PCT/AU2018/000255 Drug movement through cattle skin The transdermal route appears to be an effective and useful approach to delivering analgesic drugs to cattle.

It is more convenient and able to be applied by lay (untrained) operators.

There are regional differences in the permeability of cattle skin to topically 5 applied drugs, with thoracic/backline skin being the highest.

It was possible to move NSAIDs through cattle skin, although, of the NSAIDs registered for cattle use in Australia, only ketoprofen and flunixin meglumine were suitable, while tolfenamic acid and rneloxicam did not penetrate cattle skin.

Ketoprofen penetrated skin 10 to a significantly higher extent, but flunixin meglumine did penetrate to some degree and could be considered for other potential formulations.

Optimising a transdermal NSAID formulation A combination of 20% ketoprofen in a vehicle consisting of a combination of 50:50 15 ethanol and IPM, mixed with 10% eucalyptus oil (~7% 1,8-cineole), meaning that ethanol and 1PM are actually at 45% each, was the most effective transderrnal formulation.

This formulation was stable under a range of conditions, such as may be expected under use in the field.

Pilot studies revealed that 10 mL of the transdermal formulation delivered systemic ketofen concentrations that were likely to be effective to control pain and inflammation.

Determining the efficacy of the transdermal ketoprofen formulation WO 2019/113625 - 134 - PCT/AU2018/000255 A bioequivalence study revealed that the bioavailability of the transdermal ketoprofen formulation was~ 50%.

Importantly, the lag time was low, with active drug appearing in the systemic circulation after 15-20 min and a peak concentration~ 2 hr. A comparison with IM administration revealed that l 0 mL of the transdermal formulation had a slightly 5 longer lag time and delay to peak (CMAx), but the overall CMAx and AUC were both higher than an IM dose of 3 mg/kg.

These outcomes suggest that the transdermal formulation should therefore have similar efficacy as IM delivery.

The clinical study confirmed that similar efficacy between IM and transdermal ketoprofen 10 occurred when used during a routine surgical husbandry procedure, dehorning.

Total plasma cortisol concentrations and body weight gain showed that ketoprofen, by either route, reduced stress and pain associated with dehorning.

Behavioural parameters supported the analgesic effects of ketoprofen and, while not demonstrating overall significance, the trends were all towards analgesia and may have been significant in the 15 study had sufficient power.

Some individual behaviour parameters, such as head shaking, were significantly different from the placebo group, demonstrating that ketoprofen significantly reduced this indicator of pain.

The outcome from this project was that a formulation has been developed to effectively 20 move ketoprofen through cattle skin.

When applied to the backline, a 10 mL provided similar if not greater efficacy to control stress and pain as IM (3 mg/kg) administration.

Pharmacokinetic modelling also demonstrated a similar extent and duration of active drug following topical administration as from IM, in itself providing strong support for efficacy.

WO 2019/113625 - 135 - PCT/AU2018/000255 The transdermal ketoprofen formulation is easy to administer, effective and relatively cheap, providing a highly encouraging means of providing analgesia for surgical husbandry procedures in Australia.

This will be encouraging for producers, veterinarians and welfare advocates.

Proteomics has the potential to replace or at least support more traditional methods of assessing pain, such as plasma cortisol and behavioural parameters.

Further analysis is required to finalise the protein spectral library for cattle, before a single blood sample could accurately and quantitatively assess pain and stress.

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Claims (31)

1. CLAIMS 1. A transdermal liquid formulation comprising: (a) a therapeutically effective amount of ketoprofen or a pharmaceutically acceptable salt thereof; and (b) a dermal penetration enhancer comprising an alcohol, an emollient and eucalyptus oil.
2. 2. The transdermal liquid formulation of claim 1, wherein the ketoprofen is present in the transdermal liquid formulation at a concentration of from about 100 mg/mL to about 300 mg/mL.
3. 3. The transdermal liquid formulation of claim 1 or 2, wherein the alcohol is selected from the group consisting of a primary alcohol, a secondary alcohol and any combination thereof.
4. 4. The transdermal liquid formulation of claim 3, wherein the alcohol is selected from the group consisting of ethanol, isopropanol and any combination thereof.
5. 5. The transdermal liquid formulation of claim 4, wherein the alcohol is or comprises ethanol.
6. 6. The transdermal liquid formulation of any one of claims 1 to 5, wherein the alcohol is present in the transdermal liquid formulation at a concentration of from about 100 mL/L to about 700 mL/L.
7. 7. The transdermal liquid formulation of any one of claims 1 to 6, wherein the emollient is selected from the group consisting of a glycol, an unsaturated fatty alcohol, a sorbitol derivative, a myristate, an alkoxylated di-ester of myristyl alcohol and adipic acid, a pyrrolidone, and any combination thereof.
8. 8. The transdermal liquid formulation of Claim 7, wherein the emollient is selected from the group consisting of propylene glycol, oleyl alcohol, dimethyl isosorbide, PPG-3 benzyl ether myristate, di-PPG2-myreth-10-adipate, l-ethyl-2-pryrrolidone, isomyristate, isopropyl myristate and any combination thereof. Date Rer;ue/Date Received 2024-03-26 141
9. 9. The transdermal liquid formulation of claim 8, wherein the emollient is or comprises isopropyl myristate.
10. 10. The transdermal liquid formulation of any one of claims 1 to 9, wherein the emollient is present in the transdermal liquid formulation at a concentration of from about 100 mL/L to about 700 mL/L.
11. 11. The transdermal liquid formulation of any one of claims 1 to 10, wherein the eucalyptus oil is present in the transdermal liquid formulation at a concentration of from about 25 mL/L to about 150 mL/L.
12. 12. The transdermal liquid formulation of any one of claims 1 to 11, wherein the transdermal liquid formulation is for use in cattle.
13. 13. The transdermal liquid formulation of any one of claims 1 to 12, wherein the transdermal liquid formulation is for use as a pour-on preparation.
14. 14. A transdermal liquid formulation comprising: (a) ketoprofen at a concentration of about 100 mg/mL to about 300 mg/mL; (b) ethanol at a concentration of about 300 mL/L to about 600 mL/L; (c) isopropyl myristate at a concentration of about 300 mL/L to about 600 mL/L; and (d) eucalyptus oil at a concentration of about 50 mL/L to about 150 mL/L.
15. 15. The transdermal liquid formulation of any one of claims 1 to 14 for topical use in preventing and/or treating inflammation in a subject.
16. 16. The transdermal liquid formulation of any one of claims 1 to 14 for topical use in preventing and/or treating pain in a subject.
17. 17. The transdermal liquid formulation of any one of claims 1 to 14 for topical use in preventing and/or treating a lameness and/or a loss of mobility in a subject. Date Rer;ue/Date Received 2024-03-26 142
18. 18. The transdermal liquid formulation of any one of claims 1 to 14 for topical use in reducing stress in a subject.
19. 19. The transdermal liquid formulation for use according to any one of claims 15 to 18, wherein the transdermal liquid formulation is for use by a spray device, a pour-on device, a spot-on device and/or a transdermal patch.
20. 20. The transdermal liquid formulation for use according to of any one of claims 15 to 19, wherein the subject is bovine.
21. 21. Topical use of the transdermal liquid formulation of any one of claims 1 to 14 for preventing and/or treating inflammation in a subject.
22. 22. Topical use of the transdermal liquid formulation of any one of claims 1 to 14 for preventing and/or treating pain in a subject.
23. 23. Topical use of the transdermal liquid formulation of any one of claims 1 to 14 for preventing and/or treating a lameness and/or a loss of mobility in a subject.
24. 24. Topical use of the transdermal liquid formulation of any one of claims 1 to 14 for reducing stress in a subject.
25. 25. Use of the transdermal liquid formulation of any one of claims 1 to 14 for preparation of a topical medicament for preventing and/or treating inflammation in a subject.
26. 26. Use of the transdermal liquid formulation of any one of claims 1 to 14 for preparation of a topical medicament for preventing and/or treating pain in a subject.
27. 27. Use of the transdermal liquid formulation of any one of claims 1 to 14 for preparation of a topical medicament for preventing and/or treating a lameness and/or a loss of mobility in a subject. Date Rer;ue/Date Received 2024-03-26 143
28. 28. Use of the transdermal liquid formulation of any one of claims 1 to 14 for preparation of a topical medicament for reducing stress in a subject.
29. 29. The use according to any one of claims 21 to 28, wherein the transdermal liquid formulation is for use by a spray device, a pour-on device, a spot-on device and/ or a transdermal patch.
30. 30. The use according to of any one of claims 21 to 29, wherein the subject is bovine.
31. 31. A method of preparing the transdermal liquid formulation according to any one of claims 1 to 14, including the steps of: (a) combining a therapeutically effective amount of ketoprofen and a dermal penetration enhancer comprising an alcohol, an emollient, and eucalyptus oil; and (b) mixing the mixture of step (a) to thereby prepare the transdermal liquid formulation. Date Rer;ue/Date Received 2024-03-26