Solid transdermal therapeutic system with UV absorber

• US 20060246122A1
• Filed: 05/02/2006
• Published: 11/02/2006
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: Luye Pharma Switzerland AG (Australian Hospital Partners Holdings Pty Limited)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Bracht, Stefan, Langguth, Thomas
• Granted Patent: US 8,962,013 B2
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7038 Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Abstract

The UV-stable solid transdermal therapeutic system (TTS) with UV absorber for photosensitive active pharmaceutical ingredients has a backing layer (1), at least one active ingredient-containing matrix (2), and a detachable protective film (3). Optionally an adhesive layer (4) and a separating layer (5) are introduced between the backing layer (1) and the at least one active ingredient-containing matrix (2). At least one hydroxyphenyltriazine compound acting as UV absorber is embedded in the backing layer (1), in the active ingredient-containing matrix (2), or in the adhesive layer (4). The TTS according to the invention achieves high stability at low concentrations of UV absorber, preferably 0.5 to 3% (m/m), so as to reduce or avoid skin irritation.

Claims

1. A solid transdermal therapeutic system (TTS) with a UV absorber, said solid transdermal therapeutic system comprising a sequence of at least three layers;

wherein said at least three layers comprise a backing layer (1), at least one active ingredient-containing matrix (2), and a detachable protective film (3);

wherein optionally an adhesive layer (4) and a separating layer (5) are present between the backing layer (1) and the at least one active ingredient-containing matrix (2); and

wherein said UV absorber comprises at least one hydroxyphenyltriazine compound and said UV absorber is embedded in the backing layer (1), in the at least one active ingredient-containing matrix (2), or in the adhesive layer (4).

2. The solid transdermal therapeutic system as defined in claim 1, wherein said at least one hydroxyphenyltriazine compound is 2,4-bis-([4-(2′

-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine.

3. The solid transdermal therapeutic system as defined in claim 1, wherein the at least one active ingredient-containing matrix (2) has a weight per unit area of from 30 to 150 g/m².

4. The solid transdermal therapeutic system as defined in claim 3, wherein the weight per unit area is from 50 to 120 g/m².

5. The solid transdermal therapeutic system as defined in claim 1, wherein the adhesive layer (4) has a weight per unit area of from 5 to 50 g/m².

6. The solid transdermal therapeutic system as defined in claim 5, wherein the weight per unit area is from 20 to 30 g/m².

7. The solid transdermal therapeutic system as defined in claim 5, wherein said UV absorber is present in a concentration of from 0.5 to 5% (m/m) in dissolved form in the adhesive layer (4).

8. The solid transdermal therapeutic system as defined in claim 7, wherein said concentration of said UV absorber is from 1.0 to 4.0% (m/m).

9. The solid transdermal therapeutic system as defined in claim 1, wherein the at least one active ingredient-containing matrix (2) and the adhesive layer (4) are self-adhesive and substantially consist of at least one polymer;

wherein said at least one polymer is selected from the group consisting of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene-isoprene block polymers and polyisoprene.

10. The solid transdermal therapeutic system as defined in claim 1, wherein said separating layer (5) has a layer thickness of from 4 to 23 μ

m.

11. The solid transdermal therapeutic system as defined in claim 10, wherein said layer thickness is from 4 to 10 μ

m.

12. The solid transdermal therapeutic system as defined in claim 1, wherein said at least one active ingredient-containing matrix (2) contains an active pharmaceutical ingredient and said separating layer (5) is impermeable to said active pharmaceutical ingredient and impermeable to said UV absorber.

13. The solid transdermal therapeutic system as defined in claim 1, wherein said separating layer (5) consists of a barrier polymer and said barrier polymer is polyethylene terephthalate, polyacrylonitrile, polyvinyl chloride, polyvinylidene chloride, or a copolymer or co-laminate thereof.

14. The solid transdermal therapeutic system as defined in claim 1, wherein said at least one active ingredient-containing matrix (2) contains an active pharmaceutical ingredient, said backing layer (1) is permeable to said active pharmaceutical ingredient and said backing layer (1) consists of polypropylene, polyethylene, polyurethane, ethylene-vinyl acetate copolymer, or a multilayer composite of the foregoing polymers with one another.

15. The solid transdermal therapeutic system as defined in claim 1, wherein said UV absorber is colorless or yellowish.

16. The solid transdermal therapeutic system as defined in claim 1, which is transparent or slightly opaque.

17. The solid transdermal therapeutic system as defined in claim 1, containing an active pharmaceutical ingredient and wherein said active pharmaceutical ingredient comprises at least one hormone.

18. The solid transdermal therapeutic system as defined in claim 17, wherein said active pharmaceutical ingredient is a progestogen.

19. The solid transdermal therapeutic system as defined in claim 18, wherein said progestogen is gestodene or levonorgestrel.

20. The solid transdermai therapeutic system as defined in claim 18, consisting of a fertility controlling preparation.

24. The solid transdermal therapeutic system as defined in claim 1, containing an active pharmaceutical ingredient and without a membrane controlling release of the active pharmaceutical ingredient.

21. The solid transdermal therapeutic system as defined in 17, wherein said active pharmaceutical ingredient comprises a progestogen and an estrogen.

22. The solid transdermal therapeutic system as defined in claim 21, consisting of a fertility controlling preparation.

23. The solid transdermal therapeutic system as defined in 21, wherein said progestogen is gestodene and said estrogen is ethynyl estradiol.