WO2005046653A1

WO2005046653A1 - Antiphlogistic and analgesic plaster comprising felbinac compound

Info

Publication number: WO2005046653A1
Application number: PCT/KR2004/002965
Authority: WO
Inventors: Young Kweon Choi; Hyun Suk Yu; Young Moo Lee; Seon Mook Lim
Original assignee: ICURE
Current assignee: ICURE
Priority date: 2003-11-17
Filing date: 2004-11-16
Publication date: 2005-05-26
Anticipated expiration: 2006-05-17
Also published as: KR20050047194A; KR100552649B1

Abstract

The present invention relates to a felbinac-containing plaster, specifically, a plaster comprising felbinac (4-biphenyl acetic acid) as a NSAID anti-inflammatory agent, solubilizer, co-solvent, epidermal permeation enhancer, and pressure sensitive adhesive as a support, which can provide with long lasting anti-inflammatory effect, superior stability and adhering force to the conventional plasters therefore, it can be useful as an effective felbinac-containing plaster to treat and alleviate various inflammatory and pain inconsistently.

Description

[DESCRIPTION] [Invention Title] ANTIPHLOGISTIC AND ANALGESIC PLASTER COMPRISING FELBINAC COMPOUND [Technical Field]

[> The present invention relates to an anti-inflammatory plaster comprising felbinac (4-biphenyl acetic acid) as an effective ingredient. [Background Art] ι> Drug plaster has been introduced to the treatment of various diseases as one of TTS (Transdermal Treatment System) from long years ago. For example, the drug plaster containing various drugs such as nitroglycerin for treating angina pectoris, nicotine for abstaining from smoking, estradiol for treating various diseases caused by menopause and clonidine for lowering blood pressure has been developed and sold on the market. In contrary to topical active-substance plaster acting on specific local area, TTS shows systemic action due to distributed active substance into the circulatory blood vessel in human body which has been already absorbed through skin. > Felbinac (4-biphenyl acetic acid), one of NSAID (Non-steroidal Anti- inflammatory Drug) has been used in treating or alleviating various inflammation diseases such as rheumatic arthritis (RA), back pain, myalgia etc till now. Generally, it has been known NSAID has lots of limits to use in long term administration caused by severe adverse action for example, heart burn, gastritis, gastriorrhagia and the like as an anti-inflammatory drug since it inhibits the release of gastrointestinal protecting substance from gastric juice. Furthermore, those disadvantages together with other problems, for example, low bio-availability in oral administration requiring over dosing because of its hepatic first-pass effect and inconvenience of injectable administration have forced to develop topical preparation such as gel, liquid, cataplasm, plaster and the like till now. Among those preparations, since gel and liquid preparations have several disadvantage for example, difficulty in in-time and quantitative administration, inconvenience of administration such as possibility of dirting clothes etc and low bio- availability because of low skin-permeability, several cataplasm and plaster preparations have been developed to overcome the disadvantages of gel and liquid preparation. ι> For example, Japanese Patent No. H 4-321624 discloses ant i-inflammatory patch wherein base is styrene-isoprene-styrene block copolymer and solubiliser is crotamitone, however it has several disadvantages such as the reduction of adhesive ability because of the surface extrusion of crotamitone and the difficulty in handling crotamitone. PCT/W098/24423 discloses anti- inflammatory patch including styrene-isoprene-styrene block copolymer, rosin resin, plasticizer and felbinac without crotamitone, however it has also some problems such as inequitable needs in maximizing skin permeating rate and inducing stable release of the drug for the application period because of its low concentration of active ingredient in the patch, i.e., about 1 to 5 (w/w) %. Korean Patent No. 2002-0079811 discloses felbinac preparation of skin permeability improved by adopting water soluble additive to hot-meIt adhesive base, however it has also limits to increase the content of felbinac. > The disclosures of which above cited literatures or patents is incorporated herein by reference. > The inventors of the present invention have intensively investigated to improve and overcome the problems of conventional patch comprising felbinac till now. > As a result of the investigation, the inventors have discovered that the inventive patch can accomplish various advantages such as high- concentrated preparation of felbinac, drug stability, increased skin permeability and so on by adopting specific components; alkanolamine as a solubilizing agent, N-alkyl-pyrrolidone as a co-solvent, non-ionic surfactant, fatty acid, fatty acid derivative and the mixture thereof as epidermal permeation enhancer, and specific structured patch; multi-layered structure comprising primer layer consisting of rubber adhesive for preventing the reverse diffusion of drug from support and improving skin adhesive ability, which can maintain long-lasting ant i-inflammatory effect of felbinac and endow with superior stability and adhesive ability to conventional patches, and have finally completed the present invention. [Disclosure] [Technical Problem]

8> The present invention improve the reduction of adhesive ability due to solubilizer and organic solvent, the difficulty in handling and the demerits , low skin-permeability and the reduction of adhesive ability, because of extraction of the crystal of drug when the drug is high-concentrated in the plaster not containing solubilizer.

9> Accordingly, the present invention provide felbinac-containing plaster having long lasting anti-inflammatory effect, superior stability and adhering force to the conventional plasters therefore. [Technical Solution] o> Accordingly, it is an object of the present invention to provide novel plaster comprising felbinac (4-biphenyl acetic acid) as a NSAID anti- inflammatory agent, solubilizer, co-solvent, epidermal permeation enhancer, and pressure sensitive adhesive as a support. Specifically, present invention provide with felbinac-containing plaster comprising 1 to 25 w% felbinac (4- biphenyl acetic acid) as an active ingredient, 0.1 to 7 w% alkanolamine as a solubilizer, N-alkyl-pyrrol idone as a co-solvent, 1 to 20 w at least one epidermal permeation enhancer selected from non-ionic surfactant, fatty acid and fatty acid derivative and 30 to 90 w% pressure sensitive adhesive as a support . ι> Preferably, alkanolamine may be used as a solubilizer; N-alkyl- pyrrol idone as a co-solvent; non-ionic surfactant, fatty acid, fatty acid derivative and the mixture thereof as epidermal permeation enhancer; and acrylic adhesive, water soluble adhesive, rubber adhesive and the like as a pressure sensitive adhesive. More preferably, felbinac in an amount rnaging from about 1 to 25 w% may be used as an active ingredient; non-ionic surfactant, fatty acid, fatty acid derivative or the mixture thereof in an amount ranging from 1 to 20 w% may be used as an epidermal permeation enhancer, pressure sensitive adhesive in an amount rainging from 30 to may be used as a support . > It is another object of the present invention to provide novel plaster consisting of support layer (1) for preventing from drug diffusion as a base layer, primer layer (2) located thereon for preventing from the reverse diffusion of drug and improving skin adhesive ability, drug containing layer (3) located thereon containing felbinac thereon, and release liner (4) located at the uppermost which could be released by patient's hand. > Hereinafter the present invention shall be explained in detail as follows: > The inventive plaster according to the present invention may comprise active ingredient, solubilizer, co-solvent, epidermal permeation enhancer, pressure sensitive adhesive, and other conventionally used additives in the art. The composition in the plaster may comprise felbinac as an active ingredient in an amount of from 1 to 25 w% preferably, 3 to 20 w% more preferably, in total weight of inventive composition of which weight ratio of active ingredient can provide with optimum conditions such as good skin permeability, inconstant efficacy and stability of the drug, and economic interest. If the amount of felbinac in the composition is less than 1 w%, the sufficient efficacy of drug could not exert and if more than 25 w%, various problems, for example, extraction of drug crystal, decrease of adhesive force etc may occur. > The alkanolamine adopted by a solubilizer in the present invention has been used as a emulsifier, stabilizer, alkaline agent etc and used to increase the solubility of insoluble drug as disclosed in prior patents (United State Patent Nos. 4,678,666 and 5,436,241; European Patent No. 0276561 (BI); Korean patent No. 10-0212961). If the used amount of the agent exceeds in the amount of active ingredient, it causes to several problems such as the decrease of skin permeability or adhesive force of preparation, yellow coloring phenomenon in the process of preparation whereas the solubility of drug in the composition is increased. Therefore, present invention adopts N-alkyl-pyrrol idone as a co-solvent for increasing the drug amount in the adhesive composition before spreading and appropriate amount of alkanolamine as a solubilizer for improving the solubility of insoluble felbinac in the preparation in order to obtain purposed high concentrated felbinac plaster excluding any other disadvantages such as the decrease of adhesive ability or yellow coloring phenomenon. > In addition to above described advantages by adopting alkanolamine in the plaster of present invention, alkanolamine can increase adhesive force by acting as a plasticizer resulting in improving adhering ability to skin and accordingly improving skin permeability together with good compatibility with pressure sensitive adhesive. Preferably, methanolamine, ethanolamine, propanolamine, isopropylamine and other alkanolamines, more preferably, ethanolamine, most preferably, sole or the combination of ethanolamine selected from monoethanolamine, diethanolamine, triethanolamine and the like may be used herein in the amount of preferably, from about 0.1 to 7 w%, more preferably, 1 to 5 w% in total composition. If the amount is less than 0.1 w%, the uniformity between adhesive and felbinac is not so enough to obtain uniformed drug releasing rate whereas if the amount is more than 7 w%, the drug releasing rate may be decreased due to the interaction between alkanolamine and felbinac and the adhesive ability due to the increased amount of alkanolamine in the preparation may decrease. > N-alkyl-pyrrrol idone, preferably, N-methyl-2-pyrrolidione may be used in the present invention as a co-solvent. N-methyl-2-pyrrol idone is easily disappeared in the drying process in spite of its good solubility for felbinac therefore it can improve skin permeability and minimize skin irritation. The amount of N-alkyl-pyrrol idone ranging from 0.5 to 3 folds of the amount of felbinac can be preferably used. If the amount is less than 0.5 fold of the amount of felbinac, additional other solvent to solve felbinac is necessary and the remaining co-solvent may cause to deteriorate the physical property of plaster, i.e., adhesive force and attachment force to skin etc. > As an epidermal permeation enhancer for improving skin permeability of felbinac, non-ionic surfactant such as monoglyceride, sorbitan ester, sorbitan ester oxyethylene etc, fatty acid such as oleic acid, linoleic acid, capric acid, myristic acid etc, or fatty acid derivative such as oleyl alcohol, isopropyl myristate, propylene glycol laurate, polyethylene glycol laurate etc can be used herein. Those epidermal permeation enhancers can be use as a sole or the combination thereof in the amount ranging from 1 to 30 w%, preferably, 5 to 20 w% more preferably.

)> As a pressure sensitive adhesive in the present invention, acrylic adhesive consisting of acrylate polymer, rubber adhesive and water soluble adhesive prepared by adding several additive i.e., adhesive resin such as oil resin, rosin resin, terpene resin etc, oil, anti-oxidants to natural or synthetic rubber can be used in the present invention. Those pressure sensitive adhesive can be use as a sole or the combination thereof in the amount ranging from 30 to 90 w%, preferably, from 45 to 70 w more preferably. If the amount of the adhesive is less than 30 w%, the cohesive force of the preparation is collapsed resulting in unfavorable problems such as skin transfer etc and the amount of active ingredient and other components can be limited to use and the adherence power is lessened if more than 90 w%. o> Besides the above described components, other additives, for example, essential oil such as 1-menthol , peppermint oil etc, anti-oxidant , preservative and inorganic filler etc in the amount ranging from 0.1 to 10 w%, preferably, from 0.2 to 5 w% more preferably among total composition in of drug layer can be further added to improve the physical property of the present preparation. ι> The inventive felbinac-containing plaster of the present invention could provide all the components in the preparation with equal distribution. Accordingly, it could provide with superior advantages to conventional preparations: it can maintain the uniform distribution and high skin permeability of felbinac sufficiently and stably; accordingly, it can maintain ant i-inflammatory effect due to felbinac sufficiently for a long time; it also provide with superior stability and adherence force of the preparation. > Present invention also provide with formulated plaster depicted in Fig. 1 using by the above- described composition as an exemplary embodiment. > The felbinac-containing plaster depicted in Fig. 1 consists of four components in order to the drug be permeated through skin effectively: support layer (1) for preventing from drug diffusion as a base layer, primer layer (2) located thereon for preventing from the reverse diffusion of drug and improving skin adhesive ability, drug containing layer (3) located thereon containing felbinac thereon, and release liner (4) located at the uppermost which could be released by patient's hand. > Preferably, the support (1) is made from the materials showing good humid permeability and elasticity, which do not interact between the drug and other composition in drug layer (3). However, it is not preferable that the material of the support may effect on drug release. Synthetic resin film such as polyethylene, polypropylene, polyester and polyurethane etc, sheet, sheet foams, woven or non-woven and their laminates thereof can be preferably used as a support (3) in the present invention. Preferable thickness of the support layer ranges from 30 to 200 urn, however if the width is out of the range, the skin adhering force of patch can be worse due to the decrease of adhesive force and elasticity when the patch is applied to skin. > The primer layer (2) existed in inner side of the support (1) plays a role of preventing from the reverse diffusion of drug and improving skin adhesive ability and it consists of rubber adhesive prepared by adding several additive i.e., adhesive resin such as oil resin, rosin resin, terpene resin etc, oil, anti-oxidants to natural or synthetic rubber. Preferable thickness of the primer layer ranges from 5 to 40 urn, however if the thickness is out of the range, it could^' not prevent from the reverse diffusion of drug sufficiently or improve skin adhesive ability resulting in preventing cohesive force of adhesive agent and lowering skin adhering ability in the end, > The drug containing layer (3) consists of mainly felbinac, pressure sensitive adhesive, solubilizer, co-solvent, dispersing agent, epidermal permeation accelerator and skin irritation preventing agent or plasticizer may be added thereto if required. The drug layer containing felbinac and other components consists of mono-layer or multi-layer having more than two layers having thickness of each layer ranging from 10 to 150 um, preferably, from 20 to 120 um and thickness of total layers ranging from 30 to 500 um, preferably, from 50 to 200 um. The drug containing layer can be formed by mono layer or bi-layer of which component of each layer may be same or different from each other in order to form multi-layer laminated with each layers wherein the closest layer to skin could release felbinac most rapidly and the layer showing the slowest releasing velocity is positioned to be closest to primer layer (2) preferably.

7> The release liner (4) can be formed with polyester film coated with silicone or fluoride, polyethylene film or paper to be attached to drug containing layer (3).

8> The suitable embodiment of the felbinac-containing plaster shall be explained as follows, however, it is not intended to limit the scope of the present invention to following embodiment:

9> Appropriate combination ratio of all the compositions without alkanolamine and pressure sensitive adhesive are mixed, stirred to solve each other and remaining pressure sensitive adhesive is added thereto to form uniform sticky material. Alkanolamine is added thereto, mixed sufficiently removing air bubble. The produced material is spread onto the release liner, dried in dryer, and remaining support layer is compressed and transferred to obtain inventive plaster of the present invention. o> The plaster of the present invention can be modified and improved into well-known figure or structure in the art, for example, circle, square, rectangle, oval structure or type if required. ι> The mixing procedure described above is just intended to explain in detail and the scope of the invention is not limited to the procedure. [Advantageous Effects] ι> the inventive felbinac-containing plaster can provide with long lasting anti-inflammatory effect, superior stability and adhering force to the conventional plasters therefore, it can be useful as an effective felbinac- containing plaster to treat and alleviate various inflammation and pain inconsistently. [Description of Drawings]

?> The above and other objects and features of the present invention will become apparent from the following description, when taken in conjunction with the accompanying drawings, in which:

4> Fig. 1 presents a sectional diagram showing one embodiment example of inventive preparation;

5> Fig. 2 represents the comparison of skin permeation amount experimented in hairless mouse between the Example 1 of the present invention, comparative example and conventional plaster. [Mode for Invention]

6> The following Examples and Experimental Examples are intended to further illustrate matrix type patch formulation of the present invention without limiting its scope. > Comparative Example 1: Preparation of Comparative plaster (1) > 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer and 5 w% felbinac were added to 5 w% N-methyl-2-pyrrol idone used as a co- solvent and stirred to solve completely. 77 w% rubber adhesive was added thereto and stirred for 30 mins sufficiently. 3 w% triethanolamine used as a solubilizer was further added thereto and stirred for 30 mins removing air bubble. The mixture was spread on a release liner in order to the mixture 2 contains 0.17 mg/cm of drug and dried at 90°C for 20 mins to remove volatile co-solvent and volatile ingredient in pressure sensitive adhesive. After the drying process, the exposed dug-containing layer was closed with already prepared support layer spread with primer layer. The plaster prepared by above procedure was cut into appropriate size to prepare felbinac containing comparative plaster (1) to use as a sample in following Experimental Examples. 9> Comparative Example 2: Preparation of Comparative plaster (2) o> Comparative plaster (2) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% rubber adhesive as a pressure sensitive adhesive, 3 w% 2 triethanolamine as a solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples. ι> Comparative Example 3: Preparation of Comparative plaster (3)

2> Comparative plaster (3) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 15 w% felbinac, 70 w acrylic adhesive as a pressure sensitive adhesive, and 0.50 2 mg/cm of drug content to use as a sample in following Experimental Examples.

\3> Example 1: Preparation of inventive plaster (1) tø> Inventive plaster (1) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 5 w felbinac, 77 w% acrylic adhesive as a pressure sensitive adhesive, and 0.17 2 mg/cm of drug content to use as a sample in following Experimental Examples. β> Example 2: Preparation of inventive plaster (2) 5> Inventive plaster (2) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 10 w% felbinac, 72 w% acrylic adhesive as a pressure sensitive adhesive, and 0.34 2 mg/cm of drug content to use as a sample in following Experimental Examples. Example 3: Preparation of inventive plaster (3) ι-8> Inventive plaster (3) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 20 w% felbinac, 62 w% acrylic adhesive as a pressure sensitive adhesive, 3 w% 2 triethanolamine as a solubilizer and 0.67 mg/cm of drug content to use as a sample in following Experimental Examples. )> Example 4: Preparation of inventive plaster (4)

)> Inventive plaster (4) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% monooleic acid sorbitan used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% acrylic adhesive as a pressure sensitive adhesive, 3 w% 2 triethanolamine as a solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples. ι> Example 5: Preparation of inventive plaster (5)

2> Inventive plaster (5) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% oleic acid used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% acrylic adhesive as a pressure sensitive adhesive, 3 w% triethanolamine as a 2 solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples. > Example 6: Preparation of inventive plaster (6) > Inventive plaster (6) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting 15 w% oleylalcohol used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% acrylic adhesive as a pressure sensitive adhesive, 3 w% triethanolamine as a 2 solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples. > Example 7: Preparation of inventive plaster (7)

6> Inventive plaster (7) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting the mixture of 5 w% oleylalcohol and 10% monooleic acid sorbitane used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% acrylic adhesive as a pressure sensitive adhesive, 3 w% triethanolamine as a solubilizer and 0.50 2 mg/cm of drug content to use as a sample in following Experimental Examples. > Example 8: Preparation of inventive plaster (8) > Inventive plaster (8) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting the mixture of 15 w% monooleic acid sorbitane used as an epidermal permeation enhancer, 15 w% felbinac, 67 w% acrylic adhesive as a pressure sensitive 2 adhesive, 3 w% monoethanolamine as a solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples.

)> Example 9: Preparation of inventive plaster (9)

)> Inventive plaster (9) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting the mixture of 15 w% monooleic acid sorbitane used as an epidermal permeation enhancer, 15 w% felbinac, 65 w% acrylic adhesive as a pressure sensitive 2 adhesive, 5 w% triethanolamine as a solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples. ι> Example 10: Preparation of inventive plaster (10)

2> Inventive plaster (10) was prepared through similar procedure to the procedure disclosed in above Comparative Example 1 except adopting the mixture of 15 w% monooleic acid sorbitane used as an epidermal permeation enhancer, 15 w% felbinac, 65 w acrylic adhesive as a pressure sensitive 2 adhesive, 5 w% monoethanolamine as a solubilizer and 0.50 mg/cm of drug content to use as a sample in following Experimental Examples.

3> Experimental Example 1 > In order to examine the drug transdermal permeability of the formulations prepared by the procedures disclosed in Example 1 to 10, Comparative Example 1 to 3 and conventionally available plaster, the samples were attached to skin epidermis of four weeks old hairless mouse and then, in vitro drug permeability was measured by using Franz-diffusion cell at 32^°C . 2 The effective drug permeation area of diffusion cell was 0.64cm and the volume of solution (phosphate buffer (pH 7.4), 40% Tween 20, 1% sodium ascorbate, 0.1% sodium citrate, 0.1% sodium azide) was 5.2m£. The samples were attached to the diffusion apparatus and the PBS (pH 7.4) was used as a mobile phase. The mobile phase was stirred with a speed of 600rpm. After several times lapse from spreading 0.25 ml of mobile phase was collected to determine the amount of permeated drug and collected phase was injected to HPLC (Capsel Pack C 18, UG120, 4.6mmxl50mm, Shisheido Co. Japan) using specific condition i.e., flow rate of 1.0 ml/min, the wavelength of UV detector of 260 nm, the column temperature of 40 ^°C , the eluting solution of mixed solvent (acreonitrile: phosphate buffer solution=60: 40). The PBS was prepared by mixing 0.01M potassium phosphate with phosphoric acid to adjust the pH of 1.5 and 20 ul of each sample was injected. The drug permeation rate with time was determined in qualitative analysis and the results were shown in Table 1.

» [Table 1]

> As shown in Table 1, as the concentration of felbinac in the preparation increases, the skin permeation rate increase. It is confirmed that the skin permeation rate was affected by the sort and the content of solubilizer and epidermal permeation enhancer where same amount of felbinac were treated. If same amount of felbinac was treated in rubber adhesive, the skin permeation rate shows high however it easily extract crystal and decrease the storage-stability of preparation resulting, which has limit to put high concentrated drug. Furthermore, it is confirmed that alkanilamine used as a solubilizer could increase the drug content in stable to the extent that the preparation contains high mount of drug (about 15 w% ) providing with high skin permeability without forming of any crystal.

7> Experimental Example 2 3> In order to compare the stability of inventive plasters and comparative plasters, stability test was performed in closed and light-shielded condition with a temperature of 40 ^°C , and relative humidity of 75% and the result was shown in following Table 2.

9> [Table 2]

0> [Industrial Applicability]

'1> As mentioned above, the inventive felbinac-containing plaster can provide with long lasting ant i-inflammatory effect, superior stability and adhering force to the conventional plasters therefore, it can be useful as an effective felbinac-containing plaster to treat and alleviate various inflammation and pain inconsistently. While the invention has been described with respect to the above specific embodiments, it should be recognized that various modification and changes might be made to the invention by those skilled in the art which also fall within the scope of the invention as defined in the appended claims.

Claims

[CLAIMS] [Claim 1] A felbinac-containing plaster comprising 1 to 25 w% felbinac (4- biphenyl acetic acid) as an active ingredient, 0.1 to 7 w% alkanolamine as a solubilizer, N-alkyl-pyrrol idone as a co-solvent, 1 to 20 w% at least one epidermal permeation enhancer selected from non-ionic surfactant, fatty acid and fatty acid derivative and 30 to 90 w% pressure sensitive adhesive as a support . [Claim 2] The plaster according to claim 1, wherein said alkanolamine is selected from the group consisting of methanola ine, propanolamine, isopropanolamine and aminoalcohol . [Claim 3] The plaster according to claim 2, wherein said ethanolamine is selected from the group consisting of monoethanolamine, diethanolamine and triethanolamine. [Claim 4] The plaster according to claim 1, wherein said N-alkyl-pyrrol idone is N-methy1-pyrro1 idone . [Claim 5] The plaster according to claim 1, wherein said N-alkyl-pyrrol idone is used in the amount ranging from 0.5 to 3 folds of that of felbinac. [Claim 6] The plaster according to claim 1, wherein said non-ionic surfactant is selected from the group consisting of monoglyceride, sorbitan ester and sorbitan ester oxyethylene. [Claim 7] The plaster according to claim 1, wherein said fatty acid is selected from the group consisting of oleic acid, linoleic acid, capric acid and myristic acid. [Claim 8]

. The plaster according to claim 1, wherein said fatty acid derivative is selected from the group consisting of oleyl alcohol, isopropyl myristate, propylene glycol laurate, and polyethylene glycol laurate. [Claim 9] The plaster according to claim 1, wherein said pressure sensitive adhesive is at least one selected from the group consisting of acrylate polymer, rubber adhesive and water soluble adhesive prepared by adding adhesive resin such as oil resin, rosin resin, and terpene resin. [Claim 10] A felbinac-containing plaster consisting of support layer (1) for preventing from drug diffusion as a base layer, primer layer (2) located thereon for preventing from the reverse diffusion of drug and improving skin adhesive ability, drug containing layer (3) located thereon containing felbinac thereon, and release liner (4) located at the uppermost which could be released by patient's hand.