WO1995023596A1 - Formulations pharmaceutiques topiques depourvues d'adhesif - Google Patents

Formulations pharmaceutiques topiques depourvues d'adhesif Download PDF

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Publication number
WO1995023596A1
WO1995023596A1 PCT/EP1995/000791 EP9500791W WO9523596A1 WO 1995023596 A1 WO1995023596 A1 WO 1995023596A1 EP 9500791 W EP9500791 W EP 9500791W WO 9523596 A1 WO9523596 A1 WO 9523596A1
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WO
WIPO (PCT)
Prior art keywords
weight
pharmaceutical composition
flurbiprofen
absorbent material
ethanol
Prior art date
Application number
PCT/EP1995/000791
Other languages
English (en)
Inventor
Meena Aggarwal
John Neville Hague
Karrar Ahmad Khan
Alan Smith
Original Assignee
The Boots Company Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Boots Company Plc filed Critical The Boots Company Plc
Priority to EP95910550A priority Critical patent/EP0749301A1/fr
Priority to JP7522708A priority patent/JPH09509675A/ja
Priority to AU18502/95A priority patent/AU691583B2/en
Priority to NZ281633A priority patent/NZ281633A/en
Priority to PL95316040A priority patent/PL316040A1/xx
Priority to SK1132-96A priority patent/SK113296A3/sk
Publication of WO1995023596A1 publication Critical patent/WO1995023596A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug

Definitions

  • the present invention relates to novel topical pharmaceutical formulations, comprising a non-steroidal antiinflammatory drug (NSAID) .
  • NSAID non-steroidal antiinflammatory drug
  • the formulations may be used for the local treatment of pain and inflammation.
  • Topical formulations of NSAIDs in the form of patches which are adhered to the skin, are known. However, the removal of these patches may traumatise the skin and cause discomfort to the patient . In addition the drug may interact with the adhesive thus making it difficult to determine the actual dose received by the patient.
  • US 4,704,406 discloses sprayable preparations for the topical application of non-steroidal anti- inflammatory agents comprising a) a volatile solvent which may be ethanol, propanol or isopropanol and b) a non-volatile solvent which may be a polyfunctional alcohol or a fatty acid ester of a mono- or polyfunctional alcohol, the weight ratio of a:b being from about 1:1 to 20:1.
  • a volatile solvent which may be ethanol, propanol or isopropanol
  • a non-volatile solvent which may be a polyfunctional alcohol or a fatty acid ester of a mono- or polyfunctional alcohol, the weight ratio of a:b being from about 1:1 to 20:1.
  • these formulations suffer from the disadvantage that NSAIDs are irritant if inhaled.
  • WO 92/05768 discloses the use of S (+) -flurbiprofen in the prevention or treatment of sunburn.
  • the drug may be applied topically in any fashion suitable for topical administration.
  • a clothwipe and an impregnated bandage are listed as two, amongst many, typical topical preparations. No specific examples of such formulations are disclosed and the only assistance which the skilled reader is given is a reference to a textbook Remington's Pharmaceutical Sciences, 17th Edition 1985. However, this textbook gives no practical assistance in how to formulate a clothwipe or an impregnated bandage. Even with the incorporation of this reference the disclosure in WO 92/05768 is not enabling.
  • the present invention provides an adhesive-free topical pharmaceutical formulation comprising an absorbent material wherein the absorbent material is impregnated with a pharmaceutical composition comprising a solution of a non-steroidal anti-inflammatory drug in a C 2 _4 alcohol.
  • adhesive-free means that the formulation does not contain an adhesive (for example a silicone based adhesive or an acrylate based adhesive) to hold the absorbent material in contact with the skin.
  • an adhesive for example a silicone based adhesive or an acrylate based adhesive
  • Such formulations are particularly useful in the treatment of pain and inflammation associated with soft- tissue and musculo-skeletal injuries e.g. sports injuries.
  • the formulations ' are also useful as a supportive treatment in localised arthritic, rheumatic and inflammatory conditions. They are convenient to use, especially over large skin areas with a high density of hair and provide an immediate localised soothing and cooling effect due to evaporation of the alcohol as the drug begins to have its pharmacological effect.
  • the absorbent material may comprise any natural or synthetic material which is pharmaceutically acceptable.
  • the absorbent material comprises lint, compressed cotton, paper, cotton wool, gauze, woven or unwoven fabric or fabric which has been spun. More preferably, the absorbent material comprises compressed tissue paper, compressed cotton wool, polyester or a viscose/polyester mixture.
  • Suitable C 2 _4 alcohols are ethanol, propanol, isopropanol or n-butanol, isobutanol, sec-butanol or tert-butanol. Preferably ethanol is used. Suitably the C 2 _4 alcohol comprises 20-95% by weight of the pharmaceutical composition.
  • the non-steroidal antiinflammatory drug comprises ibuprofen, S(+) -ibuprofen, flurbiprofen, S(+)- flurbiprofen, R(-) -flurbiprofen, ketoprofen, S(+)- ketoprofen, piroxicam, or naproxen, including pharmaceutically acceptable salts of each.
  • the non-steroidal antiinflammatory drug is ibuprofen, S(+) -ibuprofen, flurbiprofen or S(+)-flurbiprofen. Most preferably S(+) -flurbiprofen is used.
  • the non-steroidal antiinflammatory drug comprises 0.1-25% by weight of the pharmaceutical composition, for example 0.1-15%.
  • the non-steroidal drug comprises 1-15%, for example 1-10%, by weight of the pharmaceutical composition, more preferably 2.5 to 7.5% by weight and most preferably 4 to 6% by weight of the pharmaceutical composition.
  • the pharmaceutical composition comprises one or more co-solvents.
  • the co-solvents are selected and optimised to achieve the desired consistency and skin-feel and to maximise the absorption of the active ingredient.
  • Suitable co-solvents are pharmaceutically acceptable excipients for the NSAID or salt thereof which are less-volatile than the C 2 _ alcohol and which prevent crystallisation of the NSAID despite evaporation of the C 2 _4 alcohol.
  • Suitable co-solvents are C 2 _ 4 alkanediols (for example 1,3-butanediol, 2,3-butanediol, 1,2-propanediol, 1,3-propanediol) , benzyl alcohol, fatty acid esters (such as isopropyl palmitate or isopropyl myristate) or polyvinylpyrrolidone.
  • the co-solvent comprises 0.01 to 90% by weight of the composition.
  • Preferred co-solvents are propylene glycol, benzyl alcohol, isopropyl palmitate, isopropyl myristate, or polyvinylpyrrolidone.
  • benzyl alcohol comprises 1-15% by weight of the pharmaceutical composition and preferably comprises 2-10% by weight of the pharmaceutical composition.
  • propylene glycol comprises 1-25% by weight of the pharmaceutical composition and preferably comprises 10-20% by weight of the pharmaceutical composition.
  • a particularly preferred co-solvent is polyvinyl ⁇ pyrrolidone.
  • polyvinylpyrrolidone has been found to form an amorphous matrix with NSAIDs, particularly with flurbiprofen or ibuprofen, or their respective S(+) -enantiomers, when an ethanolic solution is evaporated.
  • An amorphous matrix may also be formed by mixing or melting the NSAID with polyvinylpyrrolidone.
  • the optimum amount of polyvinylpyrrolidone required for each NSAID may be found by construction of a phase diagram, for example by plotting the melting point (using Differential Scanning Calorimetry) or solubility against the percentage weight of each of the components in the mixture, by methods known to those skilled in the art.
  • the polyvinylpyrrolidone comprises 0.01 to 25% by weight of the pharmaceutical composition.
  • the polyvinylpyrrolidone comprises 0.05 to 10% by weight of the pharmaceutical composition and more preferably the polyvinylpyrrolidone comprises 0.25 to 1.5% by weight of the pharmaceutical composition.
  • a preferred pharmaceutical composition comprises: 1-10% by weight of S(+)-flurbiprofen;; 0.1-10% by weight of polyvinylpyrrolidone; and 80-98.9% by weight of ethanol.
  • fatty acid esters are particularly preferred co-solvents.
  • the fatty acid ester comprises 1 to 90% by weight of the pharmaceutical composition.
  • the weight of the fatty acid ester in the composition is greater than the weight of the C _ alcohol.
  • the fatty acid ester comprises 50 to 90% by weight of the pharmaceutical composition and most preferably comprises 50 to 70% by weight of the pharmaceutical composition.
  • Preferred fatty acid esters are isopropyl palmitate and isopropyl myristate. More preferably the fatty acid ester is isopropyl palmitate.
  • a preferred pharmaceutical composition comprises: 1-10% by weight of S(+) -flurbiprofen; 1-10% by weight of benzyl alcohol; 50-70% by weight of isopropyl palmitate; and 10-48% by weight of ethanol.
  • the pharmaceutical composition comprises one or more penetration enhancers for example an aromatic oil (for example peppermint oil or eucalyptus oil), a dialkyl sulphoxide, an amide of the cyclic amine, polyoxyethylene (2) oleyl ether (available from ICI Surfactants under the trade name BRIJ 92), a fatty acid (for example oleic acid), a fatty alcohol (for example lauryl alcohol) , methyl salicylate, diethylene glycol or a surfactant.
  • the penetration enhancer comprises 0.1-10% by weight of the pharmaceutical composition and preferably comprises 0.5 to 5% by weight of the pharmaceutical composition.
  • the pharmaceutical composition may contain a thickener, such as hydroxypropyl cellulose
  • the thickener comprises 0.1 to 25% by weight of the pharmaceutical composition, preferably 0.1-5% by weight.
  • the pharmaceutical composition may contain a stabiliser to reduce esterification reactions between the C 2 _ 4 alcohol and the NSAID where the NSAID is a carboxylic acid.
  • Water is a suitable stabiliser when it comprises 5 to 30% by weight of the pharmaceutical composition.
  • the pharmaceutical composition may comprise a pharmaceutically acceptable rubefacient to provide a localised warming effect.
  • the rubefacient comprises 0.01-10% by weight of the composition.
  • the rubefacient comprises eucalyptus oil (1-5% by weight), capsaicin (0.01-0.1% by weight) , or methyl salicylate (3-7% by weight) , ethyl nicotinate (0.01 - 1% by weight) or nicotinic acid (0.01-1% by weight) .
  • the pharmaceutical composition may comprise a film forming agent such as cetostearyl alcohol.
  • the film former comprises 0.1 to 10% by weight of the pharmaceutical composition and preferably comprises 0.5 to 5% by weight of the pharmaceutical composition.
  • the pharmaceutical composition may also comprise a topically acceptable steroid, for example prednisolone, hydrocortisone, prednisone, dexamethasone, triamcinilone, betamethasone, beclomethasone, desoxymethasone, diflucorolone, fluclorolone, fluocinolone and fluorcinonide.
  • a topically acceptable steroid for example prednisolone, hydrocortisone, prednisone, dexamethasone, triamcinilone, betamethasone, beclomethasone, desoxymethasone, diflucorolone, fluclorolone, fluocinolone and fluorcinonide.
  • esters or other pharmaceutically acceptable derivatives of the above steroids may also be used.
  • the steroid comprises 0.001 to 5.0% by weight of the pharmaceutical composition, preferably 0.01 to 2.5% by weight and more preferably 0.02 to 0.5% by weight of the pharmaceutical composition.
  • the present invention comprises a process for the preparation of a pharmaceutical composition, as described above, comprising combining the NSAID or a salt thereof with the C 2 _4 alcohol and optional ingredients, for example the co-solvent, with suitable mixing.
  • suitable mixing Any mixing method known to those skilled in the art may be employed, for example stirring, shaking or other methods of mechanical agitation.
  • compositions may additionally comprise other components well known to those skilled in the art.
  • additional ingredients may comprise one or more of the following and/or any mixtures thereof: sequestrants (for example tetra sodium ethylene diamine tetra acetate dihydrate), anti-oxidants (for example DL ⁇ tocopherol acetate and/or butylated hydroxytoluene) , preservatives (for example bronopol, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolonediazolidinylurea, and/or 2- phenoxyethanol) , colouring agents (for example pharmaceutically acceptable and/or food desirable colorants and/or dyes), emollients (for example mineral oils, polymethylsiloxane, dimethicone, volatile silicone fluid, sweet almond oils, petroleum jellys and/or triglycerides of fatty acids [such as lauric triglyceride, capric/caprylic triglyceride, and
  • the partitioning potential of the pharmacologically active ingredient from the pharmaceutical composition may be optimised by examining the solubility of the active ingredient in the residual pharmaceutical composition which is obtained after evaporation of the C 2 _4 alcohol.
  • the active ingredient should be in solution at near-saturation in the residual pharmaceutical composition.
  • the active ingredient should be at saturation in the residual pharmaceutical composition and most preferably the active ingredient should be at super-saturation in the residual pharmaceutical composition. Therefore, for optimal absorption, the excipients and their proportions must be adjusted to achieve the desired level of saturation of the active ingredient on the skin after the evaporation of the volatile components.
  • An initial optimisation may be carried out by adjusting the relative amounts of the excipients and then applying the pharmaceutical composition to a glass slide. After a suitable time interval the composition is examined under a microscope for signs of crystallisation of the active.
  • phase diagrams may be constructed which may be used to obtain the optimum level of saturation required for maximum skin penetration
  • Skin penetration may be further optimised by examining the penetration of the active ingredient from test compositions or formulations through a suitable membrane, for example human cadaver skin [see Int.J.Pharm. J37_, 261-264 (1992)], or hairless mouse skin [see J.Pharm.Pharmacol, .40./ 525-529 (1987)],in a diffusion cell.
  • a suitable membrane for example human cadaver skin [see Int.J.Pharm. J37_, 261-264 (1992)], or hairless mouse skin [see J.Pharm.Pharmacol, .40./ 525-529 (1987)],in a diffusion cell.
  • a horizontal diffusion cell may be used with the membrane being placed as a barrier between two halves (a donor compartment and a receptor compartment) of the diffusion cell.
  • a specified amount of the formulation is applied to one side (the donor compartment) of the membrane which is maintained at a suitable temperature e.g. 32°C.
  • the donor compartment contains a suitable receptor solution continuously agitated and maintained at the desired temperature.
  • the receptor medium in the receptor compartment is sampled at specific time points, optionally replacing the medium as required. The samples are analysed for content of the active ingredient using appropriate qualitative, analytical techniques, for example HPLC.
  • the assay results taking into account the area available for diffusion, the volume of the receptor compartment, the receptor sample volumes, the amount of active ingredient absorbed per unit area and the percentage of the initial dose which has permeated can be calculated, and absorption profiles constructed. A suitable number of replicates should be performed.
  • the pharmaceutical formulation may be in the form of a disposable wipe.
  • the wipe may be contained in a suitable impermeable pouch to prevent evaporation on storage.
  • the wipe is wiped over the affected area so that the drug dose is applied to the skin in solution, the wipe being discarded after use.
  • the wipe may be held in contact with the affected area of the skin by any suitable means, for example by hand or by means of a bandage.
  • an impermeable backing layer may be present on one side of the wipe. Use of an impermeable backing layer reduces hand-drug contact.
  • the formulation should provide high penetration rates, since the NSAID or salt thereof remains in solution in the co- solvent on the skin, and a cooling effect.
  • the impermeable backing layer may be joined to the absorbent material at the edges or all over the surface.
  • the impermeable backing layer may be provided with pockets. The purpose of the pockets is to receive the thumb and fingers of the person applying to wipe to facilitate administration and minimise hand-drug contact.
  • the surface of the wipe for application to the skin has an area in the range 5-500cm , preferably in the range 5-100 c ⁇ r and more preferably m the range 10-40 cm 2 .
  • the dosage of the non-steroidal antiinflammatory drug applied to the skin is in the range of 0.5 mg to 10 g per cm 2 of absorbent material in contact with the skin.
  • the dosage is in the range 1-5 mg per cm 2 and more preferably the dosage is in the range 2-4 mg per cm 2 .
  • the shape of the wipe is unimportant but preferably it is square, circular or rectangular, or dumb-bell shaped.
  • the density of the absorbent material used lies in the range of 20-300 g/m 2 , for example 40-200 g/m 2 , preferably in the range 30-200 g/irr 9, for example 50-120 g/ ⁇ r9 and most preferably the density lies in the range of 60-180 g/m , for example 60-100 g/m 2 .
  • the formulation may be provided in the form of a wrap-around tissue which may be applied to joints, for example knees, ankles or elbows.
  • the wrap around tissue allows the active drug solution to remain in contact with the skin for a longer period.
  • an impermeable backing layer may be present on one side of the tissue.
  • the fabric is wrapped around the affected area, for example a joint, and optionally may be secured by an additional bandage (such as
  • the surface of the wrap-around tissue for application to the skin has an area in the range 100-500 cm 2 and preferably in the range 200-300 cm 2 .
  • the dosage ranges of non-steroidal anti-inflammatory drugs per cm 2 of absorbent material are as described for the wipe.
  • the density of the absorbent material used lies m the range of 20-300 g/m , for example 40-200 g/m , preferably m the range 30-200 g/m 2 , for example 50-120 g/m 2 and most preferably the density lies in the range of 60-180 g/m 2 , for example 60-100 g/m 2 .
  • the shape of the wrap-around is suitably circular, square, rectangular or shaped to facilitate comfortable application to a joint for example a butterfly shape or a dumb-bell shape.
  • the wrap-around is shaped for easy application to a knee, ankle, elbow, wrist, finger or toe joint.
  • Suitable impermeable backing material comprises a flexible polymer which is impermeable to the solvents used in the pharmaceutical compositions such as polyethylene or polypropylene.
  • the backing material is polyethylene.
  • the pharmaceutical formulations are prepared by cutting the absorbent material to an appropriate size, providing the material with an impermeable backing if desired and then contacting the absorbent material with the pharmaceutical composition such that the pharmaceutical composition is absorbed into the material (the latter two steps may also be carried out before cutting the absorbent material to size) .
  • Contact may be made by dipping the material into the pharmaceutical composition, spraying the pharmaceutical composition onto the material or spreading the pharmaceutical composition over the material.
  • the absorbent material may be placed in an impermeable pouch which is open at one end and the pharmaceutical composition added. The pouch is then sealed.
  • the pouch may be formed from a material which is impermeable to the pharmaceutical composition for example metal foil or a flexible polymer.
  • One preferred embodiment according to the present invention comprises an absorbent material, without adhesive, suitable for use as wipe having a first surface, to be placed in contact with the skin, with an area in the range of 10-40 cm , wherein the absorbent material is impregnated with a pharmaceutical composition comprising 2.5-7.5% by weight of a solution of S(+) -flurbiprofen in ethanol containing 0.1-10% of a co-solvent such that the effective dose is in the range 0.5 to 10 mg per cm 2 of absorbent material in contact with the skin and wherein the absorbent material has a second surface, opposite the first, provided with an impermeable backing layer of polyethylene, and further wherein the absorbent material is sealed in an impermeable pouch.
  • a pharmaceutical composition comprising 2.5-7.5% by weight of a solution of S(+) -flurbiprofen in ethanol containing 0.1-10% of a co-solvent such that the effective dose is in the range 0.5 to 10 mg per cm 2 of absorbent material in contact with the
  • a second preferred embodiment comprises an absorbent material, without adhesive, suitable for use as a wrap-around having a first surface, to be placed in contact with the skin, with an area in the range of 200-300 cm 2 , wherein the absorbent material is impregnated with a pharmaceutical composition comprising a 2.5-7.5% by weight of a solution of S(+) -flurbiprofen in ethanol containing 0.1-10% of a co-solvent such that the effective dose is in the range 0.5 to 10 mg per cirr of absorbent material in contact with the skin and wherein the absorbent material has a second surface, opposite the first, provided with an impermeable backing layer of polyethylene, and further wherein the absorbent material is sealed in an impermeable pouch.
  • the backing layer is provided with pockets.
  • Fig.l shows a plan view of a rectangular wipe with pockets
  • Fig.2 shows a cross-sectional view about the axis shown in Fig.1
  • Fig.3 & 4 show alternative shapes of wipes with pockets
  • Fig.5 shows a wipe in use
  • Fig.6 & 7 show examples of a wrap-around and product
  • Fig.8 shows a cross-section of a wrap around product.
  • Figure 2 shows a wipe comprising an absorbent layer (1) with an impermeable backing layer (2) provided with pockets (3) for insertion of the thumb and fingers as shown in Figure 5.
  • Figure 8 shows a cross-section of a wrap-around product comprising an absorbent layer (4) and an impermeable backing layer (5) .
  • the NSAID's used in this invention are commercially available or may be prepared by known methods.
  • racemic ibuprofen, racemic flurbiprofen, S(+) -ibuprofen and S(+) -flurbiprofen may be obtained from the Boots Company PLC.
  • S(+)-Ibuprofen and S(+)- flurbiprofen may also be obtained by resolving the racemic acids by methods known to those skilled in the art, for example using ⁇ -methylbenzylamine.
  • the cetostearyl alcohol was dissolved in most of the ethanol. Benzyl alcohol was added to the mixture. The flurbiprofen was dissolved in the mixture. The mixture was made up to weight with ethanol.
  • the flurbiprofen and polyvinylpyrrolidone were formed into a clear, amorphous, mass with some of the ethanol. The mass was made up to weight with the remaining ethanol.
  • composition 16 w/w
  • composition 20 % w/w
  • the flurbiprofen and isopropyl palmitate were mixed and agitated to form a suspension.
  • Benzyl alcohol was added to dissolve most of the flurbiprofen.
  • the mixture was made up to weight with the ethanol.
  • composition 21 % w/w
  • the Brij 92, propylene glycol and ethanol were mixed. Flurbiprofen was dissolved into the mixture. The Klucel was added and mixed until homogenous. The water was added slowly and stirred until a homogenous solution was obtained. Finally the solution was made up to weight with ethanol.
  • compositions 1-23 the ingredients were mixed together to form a solution, unless otherwise stated. Additional Examples are prepared by replacing S(+)- flurbiprofen by S(+) -ibuprofen, S(+) -ketoprofen, racemic flurbiprofen, racemic ibuprofen or racemic ketoprofen each of which may be present in amounts of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10% by weight. Similar % amounts of S(+)-flurbiprofen may also be used.
  • a circular piece of unwoven fabric which had a diameter of approximately 5 cm and a density of 80 g/ ⁇ r' was placed in a foil pouch open at one end.
  • a paper tissue in which the surface area of the side to be placed on a joint was 250 crcr 9 and the density of the material was 23 g/m , was placed in a foil pouch open at one end. Composition 1 (2 ml) was added and the pouch was sealed.
  • a fabric suitable for use in the above formulations comprises non-woven wet-laid fabric composed of wood pulp/viscose fibres bonded with ethyl vinyl acetate binder having the following specification:
  • polyester denotes polyester (densi • ty 171 g/irr 9 ) .

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Formulation pharmaceutique topique dépourvue d'adhésif comprenant un matériau absorbant imprégné d'une composition pharmaceutique constituée d'une solution d'une médicament anti-inflammatoire non stéroïdien dans un alcool C2-4. De façon appropriée, ce médicament anti-inflammatoire non stéroïdien comprend de l'ibuprofène, du S(+)-ibuprofène, du flurbiprofène, du S(+)-flurbiprofène, du R(-)-flurbiprofène, du kétoprofène, du S(+)-kétoprofène, du piroxicam ou du naproxène, y compris des sels pharmacologiquement acceptables de chacune de ces substances, et représente 0,1 à 25 % en poids de la composition pharmaceutique. L'alcool C2-4 représente 20 à 95 % en poids de la composition pharmaceutique. Cette composition pharmaceutique comprend, en outre, 0,01 à 90 % en poids d'un co-solvant choisi parmi le propylène glycol, l'alcool de benzyle, le palmitate d'isopropyle, le myristate d'isopropyle ou le polyvinylpyrrolidone. Cette formulation se présente, de préférence, sous la forme d'une compresse ou d'un pansement enveloppant. Ces formulations sont utiles dans le traitement local des douleurs et des inflammations.
PCT/EP1995/000791 1994-03-05 1995-03-02 Formulations pharmaceutiques topiques depourvues d'adhesif WO1995023596A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP95910550A EP0749301A1 (fr) 1994-03-05 1995-03-02 Formulations pharmaceutiques topiques depourvues d'adhesif
JP7522708A JPH09509675A (ja) 1994-03-05 1995-03-02 医薬品処方
AU18502/95A AU691583B2 (en) 1994-03-05 1995-03-02 Adhesive free topical pharmaceutical formulations
NZ281633A NZ281633A (en) 1994-03-05 1995-03-02 Topical wipe or wrap containing a non-steroidal anti-inflammatory drug (nsaid) in a 2-4c alcohol
PL95316040A PL316040A1 (en) 1994-03-05 1995-03-02 Pharmaceutic compositions
SK1132-96A SK113296A3 (en) 1994-03-05 1995-03-02 Adhesive free topical pharmaceutical formulation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9404248.8 1994-03-05
GB9404248A GB9404248D0 (en) 1994-03-05 1994-03-05 Pharmaceutical formulations

Publications (1)

Publication Number Publication Date
WO1995023596A1 true WO1995023596A1 (fr) 1995-09-08

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EP (1) EP0749301A1 (fr)
JP (1) JPH09509675A (fr)
AU (1) AU691583B2 (fr)
CZ (1) CZ258596A3 (fr)
GB (1) GB9404248D0 (fr)
NZ (1) NZ281633A (fr)
PL (1) PL316040A1 (fr)
SK (1) SK113296A3 (fr)
WO (1) WO1995023596A1 (fr)
ZA (1) ZA951781B (fr)

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EP0858805A2 (fr) * 1997-02-13 1998-08-19 National Research Institute of Chinese Medicine Préparations de'oxicames transdermales
WO2004060347A2 (fr) * 2002-09-03 2004-07-22 Transform Pharmaceuticals, Inc. Compositions pharmaceutiques de solvates de propylene glycol
AU2003243699B2 (en) * 2002-06-21 2009-01-15 Transform Pharmaceuticals, Inc. Pharmaceutical compositions with improved dissolution
WO2010050889A1 (fr) * 2008-10-31 2010-05-06 Moberg Derma Ab Composition topique comprenant une combinaison d’au moins deux agents de pénétration
EP2298280A2 (fr) 2009-09-18 2011-03-23 Sanovel Ilac Sanayi ve Ticaret A.S. Gel comprenant une combinaison de flurbiprofène et de relaxant musculaire
US7927613B2 (en) 2002-02-15 2011-04-19 University Of South Florida Pharmaceutical co-crystal compositions
US8096968B2 (en) 1999-11-08 2012-01-17 Capnia, Inc. Methods and apparatus for the enhanced delivery of physiologic agents to tissue surfaces
EP2468270A1 (fr) * 2010-12-21 2012-06-27 GALENpharma GmbH Acide (R)-2-(3-fluoro-4-phénylphényl)propionique pour une utilisation dans le traitement de maladies cutanées
WO2012151427A1 (fr) 2011-05-03 2012-11-08 Aponia Laboratories, Inc. Compositions transdermiques d'ibuprofène et leurs méthodes d'utilisation
US8398580B2 (en) 1999-11-08 2013-03-19 Capnia, Inc. Methods and apparatus for treating rhinitis
US8464711B2 (en) 1999-07-12 2013-06-18 Capnia, Inc. Methods for treating headaches
WO2013095320A1 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène
WO2013095318A2 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène à désintégration orale
WO2013095319A2 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène et de diacéréine
US9775908B2 (en) 2007-07-10 2017-10-03 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Pharmaceutical preparations containing highly volatile silicones
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US10285910B2 (en) 2001-10-12 2019-05-14 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
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US10596117B1 (en) 2014-12-31 2020-03-24 Eric Morrison Lipoleosomes as carriers for aromatic amide anesthetic compounds
US10633344B2 (en) 2002-03-01 2020-04-28 University Of South Florida Multiple-component solid phases containing at least one active pharmaceutical ingredient
US10821074B2 (en) 2009-08-07 2020-11-03 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
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US11007161B1 (en) 2014-12-31 2021-05-18 Eric Morrison Ibuprofen nanoparticle carriers encapsulated with hermatic surfactant films
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US11077068B2 (en) 2001-10-12 2021-08-03 Aquestive Therapeutics, Inc. Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US11154535B2 (en) 2012-07-31 2021-10-26 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US11191737B2 (en) 2016-05-05 2021-12-07 Aquestive Therapeutics, Inc. Enhanced delivery epinephrine compositions
US11207805B2 (en) 2001-10-12 2021-12-28 Aquestive Therapeutics, Inc. Process for manufacturing a resulting pharmaceutical film
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation

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US8464711B2 (en) 1999-07-12 2013-06-18 Capnia, Inc. Methods for treating headaches
US8096968B2 (en) 1999-11-08 2012-01-17 Capnia, Inc. Methods and apparatus for the enhanced delivery of physiologic agents to tissue surfaces
US8398580B2 (en) 1999-11-08 2013-03-19 Capnia, Inc. Methods and apparatus for treating rhinitis
US10888499B2 (en) 2001-10-12 2021-01-12 Aquestive Therapeutics, Inc. Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
US11207805B2 (en) 2001-10-12 2021-12-28 Aquestive Therapeutics, Inc. Process for manufacturing a resulting pharmaceutical film
US9931305B2 (en) 2001-10-12 2018-04-03 Monosol Rx, Llc Uniform films for rapid dissolve dosage form incorporating taste-masking compositions
US9855221B2 (en) 2001-10-12 2018-01-02 Monosol Rx, Llc Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US10285910B2 (en) 2001-10-12 2019-05-14 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
US11077068B2 (en) 2001-10-12 2021-08-03 Aquestive Therapeutics, Inc. Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US7927613B2 (en) 2002-02-15 2011-04-19 University Of South Florida Pharmaceutical co-crystal compositions
US10633344B2 (en) 2002-03-01 2020-04-28 University Of South Florida Multiple-component solid phases containing at least one active pharmaceutical ingredient
US10111810B2 (en) 2002-04-11 2018-10-30 Aquestive Therapeutics, Inc. Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
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WO2004060347A2 (fr) * 2002-09-03 2004-07-22 Transform Pharmaceuticals, Inc. Compositions pharmaceutiques de solvates de propylene glycol
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US9775908B2 (en) 2007-07-10 2017-10-03 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Pharmaceutical preparations containing highly volatile silicones
WO2010050889A1 (fr) * 2008-10-31 2010-05-06 Moberg Derma Ab Composition topique comprenant une combinaison d’au moins deux agents de pénétration
US10821074B2 (en) 2009-08-07 2020-11-03 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
US8691778B2 (en) 2009-09-18 2014-04-08 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Flurbiprofen and muscle relaxant gel combinations thereof
EP2298280A2 (fr) 2009-09-18 2011-03-23 Sanovel Ilac Sanayi ve Ticaret A.S. Gel comprenant une combinaison de flurbiprofène et de relaxant musculaire
US10940626B2 (en) 2010-10-22 2021-03-09 Aquestive Therapeutics, Inc. Manufacturing of small film strips
US10272607B2 (en) 2010-10-22 2019-04-30 Aquestive Therapeutics, Inc. Manufacturing of small film strips
WO2012084978A1 (fr) * 2010-12-21 2012-06-28 Galenpharma Gmbh Acide (r)-2-(3-fluoro-4-phénylphenyl)propionique destiné à être utilisé dans le traitement de maladies de la peau
EP2468270A1 (fr) * 2010-12-21 2012-06-27 GALENpharma GmbH Acide (R)-2-(3-fluoro-4-phénylphényl)propionique pour une utilisation dans le traitement de maladies cutanées
WO2012151427A1 (fr) 2011-05-03 2012-11-08 Aponia Laboratories, Inc. Compositions transdermiques d'ibuprofène et leurs méthodes d'utilisation
US9849080B2 (en) 2011-05-03 2017-12-26 Aponia Laboratories, Inc. Transdermal compositions of ibuprofen and methods of use thereof
AU2012250664B2 (en) * 2011-05-03 2017-04-20 Aponia Laboratories, Inc. Transdermal compositions of ibuprofen and methods of use thereof
EP3560485A1 (fr) * 2011-05-03 2019-10-30 Aponia Laboratories, Inc. Compositions transdermiques d'ibuprofène et leurs procédés d'utilisation
US11419814B2 (en) 2011-05-03 2022-08-23 Aponia Laboratories, Inc. Transdermal compositions of ibuprofen and methods of use thereof
US9205041B2 (en) 2011-05-03 2015-12-08 Aponia Laboratories, Inc. Transdermal compositions of ibuprofen and methods of use thereof
US10821071B2 (en) 2011-05-03 2020-11-03 Aponia Laboratories, Inc. Transdermal compositions of ibuprofen and methods of use thereof
EP2704703A4 (fr) * 2011-05-03 2014-12-03 Aponia Lab Inc Compositions transdermiques d'ibuprofène et leurs méthodes d'utilisation
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WO2013095318A2 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène à désintégration orale
WO2013095320A1 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène
WO2013095319A2 (fr) 2011-12-23 2013-06-27 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de flurbiprofène et de diacéréine
US11154535B2 (en) 2012-07-31 2021-10-26 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US10045935B2 (en) 2012-07-31 2018-08-14 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US11007161B1 (en) 2014-12-31 2021-05-18 Eric Morrison Ibuprofen nanoparticle carriers encapsulated with hermatic surfactant films
US10596117B1 (en) 2014-12-31 2020-03-24 Eric Morrison Lipoleosomes as carriers for aromatic amide anesthetic compounds
US10561627B2 (en) 2014-12-31 2020-02-18 Eric Morrison Ibuprofen nanoparticle carriers encapsulated with hermetic surfactant films
US11191737B2 (en) 2016-05-05 2021-12-07 Aquestive Therapeutics, Inc. Enhanced delivery epinephrine compositions
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation
US20210069137A1 (en) * 2017-12-11 2021-03-11 Meat & Livestock Australia Ltd Transdermal analgesic formulation
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NZ281633A (en) 1998-04-27
ZA951781B (en) 1995-09-05
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JPH09509675A (ja) 1997-09-30
AU691583B2 (en) 1998-05-21

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