CZ258596A3 - Topic pharmaceutical preparation without adhesive - Google Patents

Abstract

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 C2-4 alcohol. Suitably 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 and comprises 0.1-25 % by wight of the pharmaceutical composition. The C2-4 alcohol comprises 20-95 % by weight of the pharmaceutical composition. The pharmaceutical composition further comprises 0.01-90 % by weight of a co-solvent selected from propylene glycol, benzyl alcohol, isopropyl palmitate, isopropyl myristate, or polyvinylpyrrolidone. The formulation is preferably in the form of a wipe or a wrap-around. The formulations are useful for the local treatment of pain and inflammation.

Description

Technical field

The present invention relates to novel topical pharmaceutical compositions comprising a non-steroidal anti-inflammatory drug (ΧΊ-non-steroidal antiinflammatory drug). The preparation can be used for topical treatment of pain and inflammation.

BACKGROUND OF THE INVENTION

Topical formulations containing non-steroidal anti-inflammatory drugs in the form of patches that adhere to the skin are known. However, removing these patches may injure the skin and may be unpleasant for the patient. In addition, the drug may interact with the adhesive, making it difficult to determine the actual dose received by the patient.

U3 patent 4,704,406 discloses spray formulations for 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 monofunctional or polyfunctional alcohol however, these formulations have the disadvantage that non-steroidal anti-inflammatory drugs act irritably upon inhalation.

WO 92/05768 describes the use of S (+) i to prevent or treat sunburn. At 15 to 21, it is stated that the drug can flurbiprfenene on page 16 to be administered in any suitable manner for topical application. Among the many topical formulations, a drapery cloth and an impregnated dressing are named as two. There are no specific typical topical or examples of such overwrapping.

However, this textbook does not provide practical assistance in the preparation of a dressing cloth or impregnated dressing. Even when ss takes this reference into account, the description does not allow the implementation in 92 9275758.

SUMMARY OF THE INVENTION

The present invention provides an adhesive-free topical pharmaceutical composition 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 -C 4 alcohol.

Adhesive-free means that the formulation does not contain an adhesive (e.g., a silicone-based adhesive or an acrylate-based adhesive) to maintain the absorbent material in contact with the skin.

These compositions are particularly useful in the treatment of pain, and inflammation associated with soft tissue and skeletal muscle injury, e.g., sports injuries. The compositions are also useful as supportive treatments for localized arthritis and rheumatic or inflammatory conditions. They are particularly suitable for use over large areas of skin with high hair densities and provide an immediate calming and cooling effect due to the evaporation of alcohol, when the medicament begins to have its pharmaceutical effect.

Topical application of a pharmaceutical formulation in solution has the advantages of improved penetration and chemical stability due to the relatively small number of auxiliaries needed. A suitable absorbent material may be a natural or synthetic material that is pharmaceutically acceptable. The preferred absorbent material is lint, pressed cotton, paper, cotton, gauze, woven or nonwoven or spun. More preferably, the absorbent material is pressed tissue paper, pressed cotton, polyester or a viscose / polyester blend.

Suitable C 2 -C 4 alcohols are ethanol, propanol, isopropanol or π-butanol, isobutanol, sec-butanol or tert-butanol. Ethanol is preferably used. Suitably, the C 2 -C 4 alcohol comprises 20 to 5% by weight of the pharmaceutical composition.

The non-steroidal anti-inflammatory drug suitably comprises ibuorofen, 3 (· +) - ibuprofen, flurbiprofen, S (+) - flurbiprofen, R (-) - flurbiprofen, ketoprofen, S (+) - ketoprofen, piroxicam or naproxen, and pharmaceutically acceptable salts thereof . Preferably, the non-steroidal anti-inflammatory drug is ibuprofen, S (+) - ibuprofen, flurbiprofen or S (+) -flurbipr, ofene. 3 (+) - flurbiprofen is preferably used.

The pharmaceutical composition typically contains 0.1 to 25% by weight of a non-steroidal anti-inflammatory drug, for example 0.1 to 15% by weight. Preferably, the pharmaceutical composition comprises 1 to 15% by weight of a non-steroidal drug, for example 1 to 10% by weight, more preferably 2.5 to 7.5% by weight, and most preferably 4 to 6% by weight.

Preferably, the pharmaceutical composition comprises one or more co-solvents. The co-solvents are selected and optimized to achieve the desired consistency and feel to the skin as well as maximum absorption of the active ingredient. Suitable co-solvents are pharmaceutically acceptable excipients for the NSAIDs or salts thereof, which are less volatile than the C 2 -C 4 alcohol.

and which prevent crystallization of the NSA10, even if the C2 -C4 alcohol is evaporated. Suitable co-solvents are C 2 -C 4 alkanediols (e.g. 1,3-hutanediol, 2,2-butanediol, 1,2-propanediol, 1,3-propanediol), benzyl alcohol, fatty acid astars (such as isopropyl palmitate or isopropyl myristate) or polyvinylpyrrolidone.

The co-solvent preferably comprises from about 0.1% to about 90% by weight of the pharmaceutical composition. Preferred excipients are propylene glycol, benzyl alcohol, isopropyloalmitate, isopropyl myristate or polyvinylpyrrolidone. Benzyl alcohol <

Suitably, from 1 to 15% by weight of the pharmaceutical composition and preferably from 2 to 10% by weight of the pharmaceutical composition are suitably from 1 to 25% by weight of the pharmaceutical composition.

A particularly preferred co-solvent is polyvinylpyrrolidone. Unexpectedly, it has been found that polyvinylpyrrolidone forms an amorphous mass with non-steroidal anti-inflammatory drugs, in particular with flurbiprofen or ibuprofen or their respective S (+) enantiomers when the ethanol solution is evaporated. The amorphous mass can also be formed by mixing or melting the NSAID with polyvinylpyrrolidone. The optimum amount of polyvinylpyrrolidone required for each USAID can be determined by constructing a phase diagram, for example, plotting the melting point (using differential scanning calorimetry) or solubility versus weight percent of each of the components in the mixture by methods known to those skilled in the art.

The polyvinylpyrrolidone expediently constitutes 0.1 to 25% by weight of the pharmaceutical composition. Preferably, the polyvinylpyrrolidone comprises from 0.05 to 10% by weight of the pharmaceutical composition, and most preferably the polyvinylpyrrolidone comprises from 0.25 to 10% by weight of the pharmaceutical composition.

% By weight of the pharmaceutical composition.

A preferred pharmaceutical composition comprises: 1 to 13 -S bulk 3 (+) - flurbiprofen;

0.1 to 10% by weight of acetic polyvinylloyrrolidone and 6 to 9% by weight of ethanol.

Other particularly preferred co-solvents are fatty acid esters. By using these co-solvents in a high concentration, for example greater than 50% by weight of the pharmaceutical composition, an advantageous softening effect and a reduction in undesirable skin drying are achieved. The fatty acid ester tvo- ⁴ RI suitably 1-90 3 weight of the pharmaceutical composition.

The weight of the ester greater than the weight of the fatty acid in the 2-4 alcohol composition is preferably carbon atoms. More preferably, the fatty acid aster is 50 to 50% by weight of the pharmaceutical composition, and most preferably 50 to 70% by weight of the acid is less than the pharmaceutical composition. Preferred ointment esters are isopropyl palmitate and isopropyl myristate. Advantages of fatty acid isopropyl palmitate.

A preferred pharmaceutical composition comprises: 1 to 10% by weight of 3 (+) - flurbiprofen, up to 10% by weight of benzyl alcohol, up to 70% by weight of isopropyl palmitate and 10 to 43% by weight of ethanol.

The pharmaceutical composition optionally contains one or more penetration enhancers, for example, an aromatic oil (e.g., alkylsulfoxide oil, ylether amide (which may be named BP.IJ 92), peppermint or eucalyptus oil), a dicyclic amine, polyoxyethylene (2), and an OELISELY from ICI. Surfactants under commercial acid (e.g. oleic acid), a fatty alcohol (e.g. lauryl alcohol), methyl salicylate, diethylene glycol or a surfactant. The penetration enhancing agent suitably comprises 0.1 to 10% by weight of the pharmaceutical composition and 3 is preferably 0.5 up to 5% by weight of the pharmaceutical composition.

The pharmaceutical composition may optionally contain a thickening agent, such as hydroxypropylcellulose (obtainable from Aqualon under the tradename Xlucal). Sahuštovadlc consists suitably C 1-25 £ weight of the pharmaceutical composition, preferably 0.1 to 5 ^F and mass.

The pharmaceutical composition may contain a stabilizer to reduce esterification reactions between a C 2 -C 4 alcohol and a non-steroidal anti-inflammatory drug when the non-steroidal anti-inflammatory drug is a carboxylic acid. A suitable stabilizer is water when it constitutes 5 to 30% by weight of the pharmaceutical composition.

The pharmaceutical composition may optionally contain a flushing agent to achieve a localized heating effect. Suitably this agent constitutes 0.01 to 10 ¾ of the weight of the pharmaceutical composition. Preferably, the agent is eucalyptus oil (1-5%), capsaicin (0.01-0.1%) or methyl salicylate (3-7%), ethyl nicotinate (0.01-1%) or nicotinic acid. acid (0.01 to 1% by weight).

The pharmaceutical composition may optionally contain a film former such as cetostearyl alcohol. The film-forming agent expediently constitutes from 0.1 to 10% by weight of the pharmaceutical composition and preferably constitutes from 0.5 to 5% by weight of the pharmaceutical composition.

Optionally, the pharmaceutical composition may also contain a topically acceptable steroid, for example, prednisone, hydrocortisone, prednisolone, dexamethasone, triamcinolone, betamathasone, becicmethasone, desxymetasca, difluoroclone, fluclcrone, fluocinclone and fluorcinonide. Those skilled in the art will recognize that esters or other pharmaceutically acceptable derivatives of the aforementioned steroids may also be used. The steroid suitably constitutes 0.001 to 5% 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.

Another object of the present invention is to provide a process for preparing a pharmaceutical composition as described above, which comprises mixing a non-steroidal anti-inflammatory drug or a salt thereof with a C 2 -C 4 alcohol and optional ingredients, for example a co-solvent, with suitable mixing. Any of the mixing methods known to those skilled in the art can be used.

The pharmaceutical compositions may further comprise other components well known to those skilled in the art. These additional ingredients may consist of one or more of the following agents and / or any mixtures thereof: masking agents (e.g., ethylenediaminetetraacetate tetra-sodium dihydrate), antioxidants (e.g., DL-alpha-tocopherol acetate and / or butylated hydroxytoluenam), preservatives (e.g., bronopol, dehydroate) sodium, polyhexamethylenebiguanide hydrochloride, isothiazolondiazolidinylurea and / or 2-phenoxyethanol), coloring agents (e.g. pharmaceutically acceptable and / or coloring agents), plasticizers (e.g., mineral oils, polymethylsiloxane, dimethicone, volatile silicone oil, or sweet silicone oil, fatty acid triglycerides (such as lauric triglyceride, capric acid and capric acid triglyceride or / and mixed triglycerides)), humectants (e.g., D-panthenol), fragrances (e.g., pharmacy) tactically and / or cosmetically acceptable, sweet-scented oils) and wetting agents to improve the feel of the composition on the skin.

The particulate potential of the pharmacologically active ingredient of the pharmaceutical composition can be optimized by examining the solubility of the active ingredient in the remaining pharmaceutical composition obtained after evaporation of the C 2 -C 4 alcohol. In order to achieve maximum penetration into the skin, it is believed that the active ingredient should be in a solution almost saturated in the remaining pharmaceutical composition. Preferably, the active ingredient should be in a saturated solution with the remaining pharmaceutical composition, and most preferably the active ingredient should be in a supersaturated solution in the remaining pharmaceutical composition. Therefore, for optimum absorption of the excipients and their ratios, they must be adjusted to achieve the desired degree of saturation of the active ingredient on the skin after evaporation of the volatile components.

Initial optimization can be accomplished by adjusting the relative amounts of excipients and then applying the pharmaceutical composition to a slide. After a suitable time, the composition is examined under a microscope for signs of crystallization of the active ingredient.

Alternatively, the relative amounts of volatile and non-volatile components can be adjusted and the solubility of the active ingredient determined. Using these results, phase diagrams can be constructed which can be used to obtain the optimum degree of saturation required for maximum penetration into the skin.

Penetration into the skin can be further optimized by examining the penetration of the active ingredient from the test compositions or formulations through a suitable membrane, for example human cadaverous skin (see Int. J. Pharm. 87: 261-264 (1992)) or nude mouse skin (see J. Pharm. Pharmacol., 40, 525-523 (1987)) in a diffusion cuvette.

Conveniently, a horizontal diffusion cell with a membrane positioned as a partition between the two halves (donot detachment and receptor detachment) of the diffusion cell may be used. A fixed amount of preparation is applied to one side (donor separation) of the membrane, which is maintained at a suitable temperature e.g.

C. Donor separation contains a suitable receiver solution, which is continuously stirred and maintained at the desired temperature.

After the test composition has been applied to the test preparation, samples of receptor medium are taken at specified intervals in the recipe, and the medium is replaced if necessary. Samples are analyzed for active ingredient content using appropriate qualitative analytical techniques, for example, high performance liquid chromatography. Using the results of Experiments 3, taking into account the area available for diffusion, receptor compartment volume, receptor sample volumes, the amount of active ingredient absorbed per unit area and the percentage of initial dose that has penetrated can be calculated and absorption profiles can be constructed. Tests should be repeated several times.

The pharmaceutical composition may conveniently be in the form of a disposable mask. The drape may be contained in a suitable leakproof bag to prevent evaporation upon storage. As the name suggests, the drapes cover the affected area so that a dose of the drug is applied to the skin in solution, discarding the drapes after use. Optionally, the wipe can be maintained in contact with the affected skin area by any suitable means, for example by hand or by a bandage. The coating may optionally be provided with an impermeable protective layer on one side. The use of an impermeable protective layer reduces hand contact with the drug. The formulation should provide high penetration rates as the non-steroidal anti-inflammatory drug or salt thereof remains dissolved in the skin co-solvent as well as the cooling effect ... The impermeable protective layer may be attached to the absorbent material at the edges or all over the surface. Optionally, the permeable protective layer may be provided with pockets. The purpose of these pockets is to allow the person to apply the 1 C-L ”rubbing pad to insert the thumb and other fingers to facilitate application and minimize hand contact with the medicament.

Suitably, the surface of the coating for application to the skin has 2 areas in the range of 5 to 500 cm, preferably in the range of 5 to 100 cm

2 cm and more preferably in the range 10 to 40 cm. The dosage of the non-steroidal anti-inflammatory drug applied to the skin is 0.5 mg to 0.5 mg. . ,. mg per cm absorbent material in contact with the skin.

preferably, the dosage is 1-5 mg per cm, and more preferably the 2 dosage is 2-4 mg per cm. The shape of the screed is not important, but is preferably a square, circle, rectangle or barbell. The density of the absorbent material is suitably 20 to 300 g / m 2,

2, for example 40 to 200 g / m 2, preferably 30 to 200 g / m 2, e.g.

up to 120 g / cm 2 and most preferably the density is 60-130 g / m 2, for example 60-100 g / m 2.

Alternatively, the formulation may be in the form of a poultice which may be applied to the joints, for example, knees, ankles or elbows. The coating allows the active drug solution to remain in contact with the skin for an extended period of time. Optionally, one side of the fabric may be provided with an impermeable protective layer. The fabric is wrapped around the affected area, for example, the joint, and optionally attached with an additional dressing (such as Setonet) so that the impermeable protective layer is in contact with the dressing, and is removed after some time.

Tile surface used for application to the skin

Suitably, the surface area is 100 to 500 cm, and preferably 200 to 300 cm.

, _ 2

The dosage ranges of the non-steroidal orotisinflammatory drugs per cm of absorbent material are the same as those described for the overwrap. The density of the absorbent material used is suitably 20 to 300 g / m 2. for example 40 to 200 g / m, preferably 30 to 2 to 200 g / m, for example 50 to 120 g / m, and most preferably is

- η density tiC α z lc-0 g / m, napcirlac. a - 1 - ^ c c -, i

The shape of the cladding is expediently circular, square, rectangular or the cladding has a shape which allows a comfortable application to the joint, for example a butterfly or dumbbell-like shape. Preferably, the cladding is shaped to be easily applied to the knee, ankle, elbow, wrist, finger or toe.

A suitable impermeable protective material is a flexible polymer that is impermeable to solvents used in the pharmaceutical composition, such as polyethylene or polypropylene. Preferably, the protective material is polyethylene.

The pharmaceutical preparations are prepared by cutting the absorbent material into a suitable whim, optionally providing an impermeable protective layer, and then contacting the absorbent material with the pharmaceutical composition so that the pharmaceutical composition is absorbed into the material, the last two operations being The material may be contacted with the pharmaceutical composition by soaking the material in the pharmaceutical composition, spraying the pharmaceutical composition onto the material, or spreading the pharmaceutical composition onto the material. Alternatively, the absorbent material may be placed in an impermeable bag that is open on one side and the pharmaceutical composition added thereto. The bag is then sealed. The bag may be formed of a material impermeable to the pharmaceutical composition, for example a metal foil or a flexible polymer.

A preferred embodiment of the invention comprises an adhesive-free absorbent material suitable for use as a wipe, having a first surface to be contacted with the skin and having an area in the range of 10 to 40 cm, wherein the absorbent material is impregnated with a pharmaceutical composition comprising of

2.5 to 7.5% by weight of a solution of d (+) - flurbiprofen in ethanol containing 0.1 to 105% by weight of co-solvent, so that the effective dose is 0.5 to 10 mg per cm of absorbent material in contact with the skin, and wherein the absorbent material has a second surface opposite the first provided with an impermeable protective layer of polyethylene and other, wherein the absorbent material is sealed in an impermeable bag.

A second preferred embodiment consists of an adhesive-free absorbent material suitable for use as a liner having a first surface to be placed in contact with the skin and having an area in the range of 200 to 300 cm, the absorbent material being impregnated with a pharmaceutical composition comprising 5 to 7.5% by weight of a solution of S (+) - flurbiprofen in ethanol containing from 0.1 to 10% by weight of a solvent, so that the effective dose is 0.5 to 10 mg per cm of absorbent material in contact with the skin, and the absorbent material has a second surface opposite the first provided with an impermeable polyethylene protective layer and further wherein the absorbent material is sealed in an impermeable bag. The protective layer is preferably provided with pockets.

1 to 3 are examples which illustrate the invention.

Giant. Fig. 1 is a plan view of a rectangular screed mask; Fig. 2 is a sectional view taken along the axis shown in Fig. 1; Figs. 3 and 4 illustrate alternative shapes of pocket masks; Fig. 5 shows the mask in use; Figs. Fig. 3 shows a cross-section of a cladding product.

Cbr. 2 shows a wipe consisting of an absorbent layer (1) with an impermeable protective layer (2) provided with pockets (3) for receiving the thumb and other fingers, as shown in FIG. 5

Fig. Ύ shows the cross-section of the 2 absorbent layers (4) and the impermeable layers (5).

DETAILED DESCRIPTION OF THE INVENTION

The invention is illustrated by the following non-limiting findings.

Examples which the steroidal anti-inflammatory drugs used according to the invention are commercially available or can be prepared by known methods. For example, raemic ibuprofen, raeemic flurbiprofen, S (+) - ibuprofen and Si +) - flurbiprofen can be obtained from Boots Company PLC. -S (- +) - ibuprofen and 5 (-R) -flurbiprofen can also be obtained by resolution of racemic acids by methods known to those skilled in the art, for example using alpha-methylbenzylamine,

Pharmaceutical preparations

S (+) - flurbiprofen benzyl alcohol cetostearyl alcohol denatured ethanol

Composition 1 wt.

5 2 to 100 2

Composition 2 wt.

S (+) - flurbiprofen 5 benzyl alcohol 2 cetostearyl alcohol) denatured ethanol up to 100 2

- - 14% by weight |

S (t) -: lurbiprofen 5 benzyl alcohol 5 p oil1e ag1yko1 1 denatured ethanol · to 100 3 Means 4 Ϊ wt. Ξ (+) - fLurbiprofen 5 propylene glycol 10 benzyl alcohol 5 ethane1 up to 100% Means 5. % wt. 3 (+) - flurbiprofen 5 benzyl alcohol 5 cetostearyl alcohol 2 ethanol up to 100%

Cetostearyl alcohol and benzyl alcohol were added to dissolve the mixture. Ve profen. The mixture was added to 100 ^? O in most ethanol. Flurbi- ethanol. ..... Resources ’^ · - · - ~ ----------- «........ <- ........... - t • % wt. S (+) - flurbiprofen 5 propylene glycol 10, isopropyl palmitate 3 ethanol up to 100% Means 7 , .... . . ... u ....., . . ... . mass ...... S (+) - flurbiprofen 5

polyvinylpyrrolidone (Κ2ϋ) isoprocyl myristate ethanol of ICC 5

The middle of those

S (+) - flurbiprofen polyvinylpyrrolidone (K30) volatile silicone ethanol

Means 9

S (+) - fluriprofen propylene glycol benzyl alcohol ethanol

Means 10

S (+) - flurbiprofen 3ri 92 propylene glycol ethanol

o. L. _Λ

ό η., ιΟ.

y

1/5 to 10% wt.

% to ICO% wt.

T w

to ICO% ________________ "" Center, - 11 ---------------- .: 0 .......... .... ------ -------- —........- ...

% wt.

S (+) - flurbiprofen 5 *> polyvinylpyrrolidone (K90J 1 ethanol 3 ₀ i _00%

Composition 12 wt.

S (+) - Flurbiprofen 5 Solyvinyl / Rolidone (190) Efanol

Formulation 15 with (+) - flurbiprofen polyvinylpyrrolidone (190) ethanol

0,56 to ICO 3 δ mass,

0.25 to 100 3

Means 14

3 (+) - flurbiprofen polyvinyloyrrolidone (K90) ethanol wt. 5

0.1 to 100%

Composition 15 wt.

S (+) -flur’cicrofsn 5 polyvinylpyrrolidone (KjO) 0,55 ethanol up to 100%

Flurbiprofen and polyvinyloyrrolidone were processed to a clear, amorphous mass with some ethanol. Then the mass was adjusted to 100% with the remaining ethanol.

Composition ^- 16- --------------- Ξ (+) - Flurbiprofen polyvinylpyrrolidone (I <30) ethanol wt.

0.26 to 100 3

Please

Ξ (+) - urblurbipro phenol polyvinylpyrrolidone (X30) ethanol wt. ........ 5.

0.1 to 100% · /

Example 18

* 3 rolls t Ξ (+) - flurbiprofen propylene glycol 20 May ethanol to 100 Means 19 $ wt S (+) - flurbiprofen 5 isopropyl palmitate eucalyptus oil / * OU 3 benzyl alcohol 5 Brij 92 3 ethanol to 100 Means 20 % wt S (+) - flurbiprofen 5 benzyl alcohol C isopropyl palmitate SG ethanol to 100

Flurbiprofen and isopropyl palmitate were mixed and mixed to form a suspension. Benzyl alcohol was added to dissolve most of the flurbiprofen. The mixture was treated with ethanol to 100%.

% 21 wt.

S (+) - flurbiprofen 2,5 benzyl alcohol 3 isopropyl palmitate 55

Brij 32 3 eucalyptus oil 3 ethanol to ICO S

Flursiprofen and isopropyl palmitate were mixed with 2 agitated sieves to form a suspension. In order to completely dissolve flurbigrofsn, b-enyl alcohol and Srij 92 were added, followed by eucalyptus oil. Soas 33 treated with ethanol to 100%.

? eosczadat í.í.

3 (+) - flurbiprofen Klucel G? propylaaglycol Brij 92 purified water ethanol wt.

0,5 to 100%

Srij 92, propylene glycol and ethanol were mixed. Flurbiprofen was dissolved in this mixture. Klucel was added and mixed until the mass was reached. Water was added slowly and stirred until a homogeneous solution was obtained. Finally, the solution was adjusted to 100% with ethanol.

Means 23

S (+) - flurbiprofan benzyl alcohol BP eucalyptus oil B? Klucel G?

,? VP ______________ Dimsthicone ethanol

0,3 ...... 2 to 100

In the compositions 1 to 23, the individual components were mixed to form a solution unless otherwise stated.

Further examples are made by substituting 3 (+) - flurbiprofen with 5 (+) ibuprofen, 3 (+) - ketopro5ene, racemic ibuprofen, rashemic flurbiprofen or racemic ketoprofen, each of which may be present in an amount of 1, 3, 3, 3, 3,5%, 7 -o, 8 i, 9 ^? % d or 10 -5 wt. Similar = 5 amounts of S (+) - flurbiprofsin may also be used.

Example 1

A round piece of nonwoven having a diameter of approximately 2 cm and a density of 80 g / m was placed in a foil bag opened on one side. Formulation 1 (1 ml) was added to the sachet and sealed.

Example 2 (facing)

Paper slat, at the low surface area of the side that is

-. 2 should be placed on the joint, was 250 cm and the density of the material was g / m, was placed in a foil bag which was opened at one end. Formulation 1 (2 mL) was added and the bag sealed.

A substance suitable for use in the above compositions is a wet-made nonwoven fabric consisting of a mixture of cellulose and viscose fibers bonded with an ethyl vinyl acetate binder having the following properties:

mass 43 to 47 g thickness·:- ... . 200 to 240 microns tensile strength dry MD 1200 to 1500 K / m (Newtons / meter) CD 300 to 1100 M / m wet MD 500 to 300 l / m CD 350 to SOO M / m extension dry MD 7 to 10 1 CD 3 to 13% wet MD 12 to 20 S

CD 15-22 S

i) i

aosorpcm rasacita

25C c / a ⁴ fabric size: 230 x 25-0 mm fabric number: 20 nominal + 5 mm folded to J shape

Chemically / m) suitable materials include viscose (density-linked viscose (67¾) and polyester (33¾) and polyester (density 171 g / m 2).

g / m ^z ),

Claims (9)

PATENT K * 3 c ;; Y A topical adhesive-free pharmaceutical composition comprising an absorbent material, characterized in that the absorbent material is impregnated with a pharmaceutical composition comprising a solution of a non-steroidal anti-inflammatory drug in an alcohol comprising 2 to 4 carbon atoms. ..2 '. The composition of claim 1, wherein the non-steroidal anti-inflammatory drug is ibuprofen, S (Ή-ibuprofen, flurbiprofen, S (+) - flurbiprofen, R (-) - flurbiprofen, ketoprofen, S (+) - ketoprofen, piroxicam or naproxen, and pharmaceutically acceptable salts thereof, and constitute from 0.1 to 25% by weight of the pharmaceutical composition. Composition according to claims 1 or 2, characterized in that the alcohol having 2 to 4 carbon atoms is selected from the group consisting of ethanol # propanol, isopropanol, n-butanol, isobutanol, sak.butanol and tert-butanol and is 20 to 95 5 by weight of the pharmaceutical composition. - • r i Λ 4. A composition according to any one of claims 1 to 3 wherein the pharmaceutical composition further comprises from 0.01 to 50% by weight of a co-solvent selected from the group consisting of propylene glycol, benzyl alcohol, isopropyl palmitate, isopropyl myristate and polyvinyloyrrolidone. A formulation according to claim 4 wherein the co-solvent is polyvinylpyrrolidone and comprises from 0.01 to 25% by weight of the pharmaceutical ingredient. 6 ·. A composition according to claim 5, wherein the pharmaceutical composition comprises: 1 to 13% by weight of 3 (+) - flurbiprofen, 0.1 to 10% by weight of polyvinylpyrrolidone and 30 to 33.9% by weight of ethanol. 7. A composition according to claim 4, comprising the composition. The composition according to claim 1, wherein the co-solvent is isopropyloaluminum in greater than 50% by weight of pharmaceutical 3. A composition according to claim 7, wherein the pharmaceutical composition comprises: 1-10% by weight of 3 (+) - flurbiprofen, 1 to 10% by weight of benzyl alcohol, 50 to 70% by weight of isopropyl palmitate; and 10 to 43% by weight of ethanol. , .- Λ A composition according to claim 1 suitable for use as a wipe, having a first surface to be placed in contact with the skin having an area in the range of 10 to 40 tin, characterized in that the absorbent material is impregnated with a pharmaceutical composition comprising: , 5 to 7.5% by weight of a solution of 3 (+) - flurbiprofen in ethanol containing from 0.1 to 10% by weight of a co-solvent such that the effective dose is in the range of 0.5 to 10 mg per cm of absorbent material in contact with wherein the absorbent material has a second opposite surface that is provided with an impermeable protective layer of polyethylene, and wherein the absorbent material is sealed in an impermeable bag. A composition according to claim 1 suitable for use as a pouch having a first surface to be placed in contact with the skin having an area in the range of 200 to 300 cm, characterized in that the absorbent material is impregnated with a pharmaceutical composition consisting of 2.5 to 7.5% by weight of a solution of 3 (+) - flurbiprofen in ethanol containing 0.1 to 10% by weight of the co-solvent, so that an effective dose is in the range of 0.5 to 10 mg per cm of absorbent material in contact with the skin wherein the absorbent material has a second surface opposite the first which is provided with an impermeable polyethylene protective layer and wherein the absorbent material is sealed in an impermeable bag.