UV stable transdermal therapeutic plaster with a UV absorbing self-adhesive layer separated from the drug matrix
The invention relates to a UV stable transdermal therapeutic system (TTS) consisting of a back layer, at least one matrix containing an active substance and optionally, a withdrawal film and an UV-radiation absorber. An adhesive layer containing said UV-radiation absorber is arranged between the back layer and the matrix containing an active substance which is distant as much as possible from a surface, a separation layer is arranged between the adhesive layer containing said UV-radiation absorber and the matrix containing an active substance, which is as remote as possible from the surface which is impermeable to the active substance and UV-radiation absorber. The inventive transdermal therapeutic system exhibits a high stability and is devoid of inconveniences of existing TTS containing a light-sensitive substance.
1. A transdermal therapeutic system (TTS) consisting of: a backing layer, at least one UV-absorber containing self-adhesive layer, at least one separating layer, at least one active ingredient-containing matrix layer, and optionally a detachable sheet, wherein:
i) the at least one UV absorber-containing self-adhesive layer is provided between the backing layer and the active ingredient-containing matrix layer which is furthest away from the surface of the skin,
ii) the at least one active ingredient-containing matrix layer contains at least one active ingredient which is a photosensitive active ingredient,
iii) the at least one separating layer has a layer thickness of from 4 to 23 μm, is impermeable to the active ingredient and impermeable to the UV absorber, and at least one separating layer is present between the UV absorber-containing self-adhesive layer and the active ingredient-containing matrix layer which is furthest away from the surface of the skin.
2. A transdermal therapeutic system according to claim 1 , wherein the sequence of layers in the system starting from the side facing away from the skin is backing layer, UV absorber-containing self-adhesive layer, separating layer, and a mono- or bilayer active ingredient-containing matrix layer having a pressure-sensitive adhesive surface which is covered by a detachable protective sheet.
3. A transdermal therapeutic system according claim 1 , wherein the weight per unit area of the UV absorber-containing self-adhesive layer is from 5 to 50 g/m 2 .
4. A transdermal therapeutic system according to claim 1 , wherein the separating layer consists of a barrier polymer comprising polyethylene terephthalate, poly-acrylonitrile, polyvinyl chloride, polyvinylidene chloride or copolymers or colaminates thereof.
5. A transdermal therapeutic system according to claim 1 , wherein the active ingredient-containing matrix layer is self-adhesive and comprises a polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene/isoprene block polymer or polyisoprene polymer.
6. A transdermal therapeutic system according claim 1 , wherein the weight per unit area of the active ingredient-containing matrix layer(s) is from 30 to 150 g/m 2 .
7. A transdermal therapeutic system according to claim 1 , wherein the backing layer is permeable to the active ingredient and comprises polypropylene, polyethylene, polyurethane, ethylene/vinyl acetate copolymer or a multilayer composite of these materials with one another or with other materials.
8. A transdermal therapeutic system according to claim 1 , wherein the UV absorber is present in dissolved form in the UV absorber-containing self-adhesive layer in a concentration of from 0.5 to 10% (m/m).
9. A transdermal therapeutic system according to claim 1 , wherein the UV absorber(s) are contained only in the UV absorber-containing self-adhesive layer.
10. A transdermal therapeutic system according to claim 1 , wherein at least one UV absorber is selected from the group consisting of: p-aminobenzoic acid, 2-ethylhexyl 4-dimethylaminobenzoate, polyethoxyethyl 4-bis(polyethoxyl)aminobenzoate, cinnamic acid, isoamyl 4-methoxycinnamate, 2-ethylhexyl 4-methoxycinnamate, 3-benzylidenebornan-2-one, 3-(4′)-methylbenzylindenebornan-2-one, 3-(4-sulphone)benzylindenebornan-2-one, 3-(4′-trimethylammonium)-benzylidenebornan-2-one methylsulphate, 4-isopropylbenzyl salicylate, 2-ethylhexyl salicylate, 3,3,5-trimethylcyclohexyl salicylate, 2-(5-chloro-2H-benzotriazole-2-yl)-6-(1,1-dimethylethyl)-4-methylphenol, 2,4,6′-trianiline-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine, 3-imidazol-4-ylacrylic acid, 3-imidazol-4-yl-3-imidazol-4-ylacrylic ester, 2-phenylenebenzimidazole-5-sulphonic acid or its K, Na, or triethanolamine salts, 2-cyano-3,3-diphenylacrylic acid, terephthaloylidenedicamphorsulphonic acid, butylmethoxydibenzoylmethane, benzophenone, benzophenone-3, and benzophenone-4.
11. A transdermal therapeutic system according to claim 1 , wherein the UV absorber(s) is/are colourless or yellow.
12. A transdermal therapeutic system according to claim 1 , wherein the system is transparent.
13. A transdermal therapeutic system according to claim 1 , wherein the active ingredient comprises at least one hormone.
14. A transdermal therapeutic system according to claim 1 , wherein the active ingredient comprises a progestogen.
15. A transdermal therapeutic system according to claim 1 , wherein the active ingredient comprises gestodene or levonorgestrel.
16. A transdermal therapeutic system according to claim 1 , wherein the active ingredient comprises gestodene.
17. A transdermal therapeutic system according to claim 1 , wherein said separating layer comprises a polyethylene terephthalate barrier polymer.
18. A transdermal therapeutic system according to claim 1 , wherein said backing layer comprises a polyethylene.
19. A transdermal therapeutic system according to claim 1 , wherein at least one active ingredient-containing matrix and/or at least one UV absorber-containing self-adhesive layer comprise a polymer selected from the group consisting of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene/isoprene block polymer, polyisoprene and combinations thereof.
20. A transdermal therapeutic system according to claim 1 , wherein the weight per unit area of the UV absorber-containing self-adhesive layer is from 20 to 30 g/m 2 .
21. A transdermal therapeutic system according to claim 1 , wherein the separating layer has a layer thickness of from 4 to 10 μm.
22. A transdermal therapeutic system according to claim 1 , wherein the weight per unit area of the active ingredient-containing matrix layer is from 50 to 120 g/m 2 .
23. A transdermal therapeutic system according to claim 1 , wherein the UV absorber is present in dissolved form in the UV absorber-containing self-adhesive layer in a concentration of from 1.0 to 5.0% (m/m).