DERMAL THERAPEUTIC SYSTEM WITH HIGH ADHESIVITY

Abstract

The present invention relates to a high adhesion dermal therapeutic system comprising an adhesive polymeric matrix with a salt of Diclofenac.

Claims

1. A dermal therapeutic system which comprises an adhesive polymeric matrix comprising an acrylate-vinyl acetate copolymer having a Tg below 0° C., preferably self-curing, which contains free hydroxyl groups, said acrylate-vinyl acetate copolymer being present in a percentage ranging from 45 to 65% by weight with respect to the total dry weight of the adhesive polymeric matrix and a basic butylated methacrylate copolymer, said methacrylate copolymer being present in a percentage ranging from 5 to 20% by weight with respect to the total dry weight of the adhesive polymeric matrix, as adhesive components, an organic or inorganic acid in a percentage ranging from 0.5 to 3.5% by weight with respect to the total dry weight of the adhesive polymeric matrix, as stabilizer, a salt of Diclofenac in a percentage ranging from 8 to 20% by weight with respect to the total dry weight of the adhesive polymeric matrix, as active principle, the complement to 100 consisting of excipients and/or pharmaceutically acceptable additives, such as, for example, adhesion modulators.

2. The dermal therapeutic system according to claim 1, wherein the acrylate-vinyl acetate copolymer having a Tg below 0° C., containing free hydroxyl groups, is the copolymer Duro-tak® 387-2516/87-2516 or the copolymer Duro-tak® 387-2287/87-2287, and is preferably the self-curing copolymer Duro-tak® 387-2516/87-2516.

3. The dermal therapeutic system according to one or more of the previous claims claim 1, wherein the acrylate-vinyl acetate copolymer is present in a percentage ranging from 50 to 60%, preferably from 53 to 58% by weight with respect to the total dry weight of the adhesive polymeric matrix.

4. The dermal therapeutic system according to claim 1, wherein the basic butylated methacrylate copolymer is the copolymer Eudragit® E100, i.e. a dimethylaminoethyl methacrylate copolymer having the following structure: ##STR00002##

5. The dermal therapeutic system according to claim 1, wherein the basic butylated methacrylate copolymer is present in a percentage ranging from 6 to 16%, preferably from 9 to 13% by weight with respect to the total dry weight of the adhesive polymeric matrix.

6. The dermal therapeutic system according to claim 1, wherein the salt of Diclofenac is selected from salts of alkaline metals, such as sodium salt or potassium salt, or the Diclofenac is salified with hydroxyethylpyrrolidine or it is a diethylammonium salt, preferably in a percentage ranging from 10 to 20%, even more preferably in a percentage ranging from 12 to 16% by weight with respect to the total dry weight of the adhesive polymeric matrix.

7. The dermal therapeutic system according to claim 1, wherein the salt of Diclofenac is selected from sodium salt or diethylammonium salt, preferably sodium salt.

8. The dermal therapeutic system according to claim 1, wherein the polymeric matrix also includes adhesion modulators, preferably polyethylene glycol (12 moles) stearate and/or sorbitan oleate, in a total percentage ranging from 10 to 30%, preferably from 12 to 25%, even more preferably from 15 to 20% by weight with respect to the total dry weight of the adhesive polymeric matrix.

9. The dermal therapeutic system according to claim 1, wherein the organic or inorganic acids, are selected from hydrochloric acid or mono, di or tricarboxylic organic acids, more preferably citric, succinic, lactic, maleic, fumaric, salicylic or acetic acid, in a percentage ranging from 0.5 to 3.5%, preferably from 0.8 to 2.5%, even more preferably from 1 to 2% by weight with respect to the total dry weight of the adhesive polymeric matrix.

10. The dermal therapeutic system according to claim 1, wherein the organic acid is citric acid monohydrate.

11. The dermal therapeutic system according to claim 1, wherein the adhesive polymeric matrix has the following composition: 56% by weight with respect to the total dry weight of the adhesive polymeric matrix, of Duro-tak 387-2516/87-2516; 11.1% by weight with respect to the total dry weight of the adhesive polymeric matrix, of Eudragit E100; 13.4% by weight with respect to the total dry weight of the adhesive polymeric matrix, of sodium Diclofenac; 13.4% by weight with respect to the total dry weight of the adhesive polymeric matrix, of polyethylene glycol (12 moles) stearate; 4.5% by weight with respect to the total dry weight of the adhesive polymeric matrix, of sorbitan oleate; 1.6% by weight with respect to the total dry weight of the adhesive polymeric matrix, of citric acid monohydrate.

12. The dermal therapeutic system according to claim 1, wherein the adhesive polymeric matrix has the following composition: 54.8% by weight with respect to the total dry weight of the adhesive polymeric matrix, of Duro-tak 387-2516/87-2516; 10.8% by weight with respect to the total dry weight of the adhesive polymeric matrix, of Eudragit E100; 15.3% by weight with respect to the total dry weight of the adhesive polymeric matrix, of Diclofenac diethylammonium salt; 13.1% by weight with respect to the total dry weight of the adhesive polymeric matrix, of polyethylene glycol (12 moles) stearate; 4.4% by weight with respect to the total dry weight of the adhesive polymeric matrix, of sorbitan oleate; 1.6% by weight with respect to the total dry weight of the adhesive polymeric matrix, of citric acid monohydrate.

13. The dermal therapeutic system according to claim 1, wherein the adhesive polymeric matrix has a thickness ranging from 50 to 500 microns, preferably from 100 to 350 microns, and even more preferably a thickness equal to about 300 micron.

14. The dermal therapeutic system according to claim 1, which also comprises a backing layer of the adhesive polymeric matrix, preferably a 100% polyester non-woven fabric, and a protective layer preferably selected from a siliconized polyester film, a non-woven polyester fabric, a mono-siliconated glassine paper.

15. The dermal therapeutic system according to claim 1, having a surface ranging from 20 to 300 cm.sup.2, preferably from 100 to about 150 cm.sup.2.

16. The dermal therapeutic system according to claim 2, wherein the acrylate-vinyl acetate copolymer is present in a percentage ranging from 50 to 60%, preferably from 53 to 58% by weight with respect to the total dry weight of the adhesive polymeric matrix.

17. The dermal therapeutic system according to claim 2, wherein the basic butylated methacrylate copolymer is the copolymer Eudragit® E100, i.e. a dimethylaminoethyl methacrylate copolymer having the following structure: ##STR00003##

18. The dermal therapeutic system according to claim 3, wherein the basic butylated methacrylate copolymer is the copolymer Eudragit® E100, i.e. a dimethylaminoethyl methacrylate copolymer having the following structure: ##STR00004##

19. The dermal therapeutic system according to claim 2, wherein the basic butylated methacrylate copolymer is present in a percentage ranging from 6 to 16%, preferably from 9 to 13% by weight with respect to the total dry weight of the adhesive polymeric matrix.

20. The dermal therapeutic system according to claim 3, wherein the basic butylated methacrylate copolymer is present in a percentage ranging from 6 to 16%, preferably from 9 to 13% by weight with respect to the total dry weight of the adhesive polymeric matrix.

Description

EXAMPLE 1

Preparation of a Dermal Therapeutic System Containing Diclofenac Sodium Salt.

[0075] 16.46 g of ethyl acetate were mixed under mechanical stirring with 16.70 g of isopropanol. 12.94 g (11.11% by weight with respect to the total dry weight of the adhesive polymeric matrix) of Eudragit E100 (dimethylaminoethyl methacrylate copolymer) were added to this mixture of solvents and the whole mixture was left under vigorous stirring at room temperature until complete dissolution. 15.58 g (13.37% by weight with respect to the total dry weight of the adhesive polymeric matrix) of sodium Diclofenac were then added under stirring and 7.99 g of water under vigorous stirring for about 5 minutes.

[0076] The mixture was then heated to 40° C. and 15.66 g (13.44% by weight with respect to the total dry weight of the adhesive polymeric matrix) of polyethylene glycol (12 moles) stearate (Cithrol 6MS) were subsequently added under vigorous stirring until complete dissolution. 5.27 g (4.52% by weight with respect to the total dry weight of the adhesive polymeric matrix) of sorbitan oleate (Span 80V) were then added under stirring until complete dissolution, followed by 1.9 g (1.63% by weight with respect to the total dry weight of the adhesive polymeric matrix) of citric acid monohydrate under stirring until complete dissolution, and finally 157.49 g (55.94% by weight with respect to the total dry weight of the adhesive polymeric matrix) of Duro-tak 387-2516/87-2516 (acrylate-vinyl acetate copolymer having a Tg lower than 0° C., self-curing, which comprises free hydroxyl groups), having a solid content of 41.5% w/w, under slow stirring, until about 250 g of a homogeneous mass were obtained.

[0077] For preparing the layer of adhesive polymeric matrix, the mixture was spread on a siliconated glassine paper (80 g/m.sup.2) having a thickness of 300 microns, using a manual spreader. The solvents were removed in an air-circulation oven by heating to 60° C. for 40 minutes.

[0078] A lamination was then effected, using a 100% polyester nonwoven fabric as support.

EXAMPLE 2

[0079] Preparation of a Dermal Therapeutic System Containing Diclofenac Salified with Diethylammonium.

[0080] This system was prepared following the same procedure described in Example 1, but 17.8 g (i.e. 15.3% by weight with respect to the total dry weight of the adhesive polymeric matrix) of Diclofenac diethylammonium salt were added instead of the sodium salt. At the end of the preparation process, a lamination was effected using a 100% polyester nonwoven fabric as support.

Adhesiveness Tests in Vitro

[0081] Various adhesive matrixes were prepared for this purpose (as comparison) as described in Example 1, substituting PSA Duro-Tak 87/2516 with a PSA containing carboxyl groups.

Preparation of the Comparative Adhesive Matrix

[0082] The comparative adhesive matrix was prepared according to the same procedure described in Example 1, substituting Duro-tak 387-2516/87-2516 with Duro-tak 87/2852, i.e. using 157.49 g of an acrylate copolymer having a Tg lower than 0° C., cured, that comprises up to 7% of free carboxyl groups, having a solid content of 33.5% w/w. The addition was effected under slow stirring, until about 250 g of a homogeneous mass were obtained. At the end of the preparation process, a lamination was effected using a 100% polyester nonwoven fabric as support.

Adhesion on a Steel Support Expressed in N/cm

[0083]

TABLE-US-00001 Adhesive- Adhesive- Adhesive- Preservation ness ness ness Sample conditions Time 0 1 month 3 months Example 1 25° C. ± 2° C./ 12.02 N/cm 9.3 N/cm 7.8 N/cm Example 1 40° C. ± 2° C./ 12.02 N/cm 7.4 N/cm 6.7 N/cm Comparative 25° C. ± 2° C./ 6.1 N/cm 5.8 N/cm 2.9 N/cm plaster (Duro-tak ® 87-2852) Comparative 40° C. ± 2° C./ 6.1 N/cm 4.9 N/cm 2.3 N/cm plaster (Duro-tak ® 87-2852)

[0084] The tests carried out according to the procedure described above show that the adhesiveness of the therapeutic system according to the present invention is approximately double with respect to the adhesiveness of the comparative plaster, at both 25° C. and at 40° C.

[0085] The particular combination of elements forming the formulation of the adhesive polymeric matrix of the therapeutic system according to the present invention thus allows a high adhesiveness to be obtained, which is stable with time also at different temperatures.