MULTI-LAYERED TRANSDERMAL SYSTEM WITH TRIAZINE UV ABSORBER
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 it 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.
1 .- 24 . (canceled)
25 . A solid transdermal therapeutic system (TTS) with a UV absorber, said solid transdermal therapeutic system comprising a sequence of at least five layers;
wherein said at least five layers comprise a backing layer ( 1 ), an adhesive layer ( 4 ), a separating layer ( 5 ), at least one active ingredient-containing matrix ( 2 ), and a detachable protective film ( 3 );
wherein the adhesive layer ( 4 ) is between the backing layer ( 1 ) and the separating layer ( 5 ), the separating layer ( 5 ) is between the adhesive layer ( 4 ) and the at least one active ingredient-containing matrix ( 2 ), and the at least one active ingredient-containing matrix ( 2 ) is between the separating layer ( 5 ) and the detachable protective film ( 3 );
wherein said UV absorber consists of 2,4-bis-([4-(2′-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine as the sole UV absorber in the system, said UV absorber is present in a concentration of from 0.5 to 4.0% (m/m) in dissolved form in the adhesive layer and said UV absorber is also optionally present in the backing layer ( 1 ); and
wherein the solid transdermal therapeutic system is transparent.
26 . The solid transdermal therapeutic system as defined in claim 25 , wherein the at least one active ingredient-containing matrix ( 2 ) has a weight per unit area of from 30 to 150 g/m 2 .
27 . The solid transdermal therapeutic system as defined in claim 26 , wherein the weight per unit area of the at least one active ingredient-containing matrix ( 2 ) is from 50 to 120 g/m 2 .
28 . The solid transdermal therapeutic system as defined in claim 25 , wherein the adhesive layer ( 4 ) has a weight per unit area of from 5 to 50 g/m 2 .
29 . The solid transdermal therapeutic system as defined in claim 28 , wherein the weight per unit area of the adhesive layer ( 4 ) is from 20 to 30 g/m 2 .
30 . The solid transdermal therapeutic system as defined in claim 25 , wherein said concentration of said UV absorber is from 1.0 to 2.0% (m/m) in dissolved form in the adhesive layer ( 4 ).
31 . The solid transdermal therapeutic system as defined in claim 25 , wherein the at least one active ingredient-containing matrix ( 2 ) and the adhesive layer ( 4 ) are self-adhesive and comprise 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.
32 . The solid transdermal therapeutic system as defined in claim 25 , wherein said separating layer ( 5 ) has a layer thickness of from 4 to 23 μm.
33 . The solid transdermal therapeutic system as defined in claim 32 , wherein said layer thickness is from 4 to 10 μm.
34 . The solid transdermal therapeutic system as defined in claim 25 , 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.
35 . The solid transdermal therapeutic system as defined in claim 25 , 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.
36 . The solid transdermal therapeutic system as defined in claim 25 , 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.
37 . The solid transdermal therapeutic system as defined in claim 25 , wherein said UV absorber is colorless or yellow.
38 . The solid transdermal therapeutic system as defined in claim 25 , containing an active pharmaceutical ingredient and wherein said active pharmaceutical ingredient comprises at least one hormone.
39 . The solid transdermal therapeutic system as defined in claim 38 , wherein said active pharmaceutical ingredient is a progestogen.
40 . The solid transdermal therapeutic system as defined in claim 39 , wherein said progestogen is gestodene or levonorgestrel.
41 . The solid transdermal therapeutic system as defined in claim 39 , which is effective as a fertility controlling preparation.
42 . The solid transdermal therapeutic system as defined in 38 , wherein said active pharmaceutical ingredient comprises a progestogen and an estrogen.
43 . The solid transdermal therapeutic system as defined in claim 42 , which is effective as a fertility controlling preparation.
44 . The solid transdermal therapeutic system as defined in claim 25 , containing an active pharmaceutical ingredient and without a membrane controlling release of the active pharmaceutical ingredient.
45 . The solid transdermal therapeutic system as defined in claim 25 , wherein said separating layer comprises a polyethylene terephthalate.
46 . The solid transdermal therapeutic system as defined in claim 25 , wherein said backing layer comprises a polyethylene.
47 . A solid transdermal therapeutic system (TTS) with a UV absorber, said solid transdermal therapeutic system comprising a sequence of at least five layers;
wherein said at least five layers comprise a backing layer ( 1 ), an adhesive layer ( 4 ), a separating layer ( 5 ), at least one active ingredient-containing matrix ( 2 ), and a detachable protective film ( 3 );
wherein the adhesive layer ( 4 ) is between the backing layer ( 1 ) and the separating layer ( 5 ), the separating layer ( 5 ) is between the adhesive layer ( 4 ) and the at least one active ingredient-containing matrix ( 2 ), and the at least one active ingredient-containing matrix ( 2 ) is between the separating layer ( 5 ) and the detachable protective film ( 3 );
wherein said UV absorber consists of 2,4-bis-([4-(2′-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine as the sole UV absorber in the system, said UV absorber is present in a concentration of from 0.5 to 4.0% (m/m) in dissolved form in the adhesive layer and said UV absorber is also optionally present in the backing layer ( 1 ); and
wherein the solid transdermal therapeutic system is transparent; and
wherein the active ingredient comprises gestodene and ethinyl estradiol.
48 . The solid transdermal therapeutic system as defined in claim 47 , wherein the at least one active ingredient-containing matrix ( 2 ) has a weight per unit area of from 30 to 150 g/m 2 .
49 . The solid transdermal therapeutic system as defined in claim 47 , wherein the weight per unit area of the at least one active ingredient-containing matrix ( 2 ) is from 50 to 120 g/m 2 .
50 . The solid transdermal therapeutic system as defined in claim 47 , wherein the adhesive layer ( 4 ) has a weight per unit area of from 5 to 50 g/m 2 .
51 . The solid transdermal therapeutic system as defined in claim 50 , wherein the weight per unit area of the adhesive layer ( 4 ) is from 20 to 30 g/m 2 .
52 . The solid transdermal therapeutic system as defined in claim 47 , wherein said UV absorber is present in a concentration of from 0.5 to 2.5% (m/m) in dissolved form in the adhesive layer ( 4 ).
53 . The solid transdermal therapeutic system as defined in claim 47 , wherein said UV absorber is present in the adhesive layer ( 4 ).
54 . The solid transdermal therapeutic system as defined in claim 47 , wherein the at least one active ingredient-containing matrix ( 2 ) and the adhesive layer ( 4 ) are self-adhesive and comprise at least one polyisobutylene polymer.
55 . The solid transdermal therapeutic system as defined in claim 47 , wherein said separating layer ( 5 ) has a layer thickness of from 4 to 23 μm.
56 . The solid transdermal therapeutic system as defined in claim 55 , wherein said layer thickness is from 4 to 10 μm.
57 . The solid transdermal therapeutic system as defined in claim 47 , wherein said at least one active ingredient-containing matrix ( 2 ) contains the active pharmaceutical ingredient and said separating layer ( 5 ) is impermeable to said active pharmaceutical ingredient and impermeable to said UV absorber.
58 . The solid transdermal therapeutic system as defined in claim 47 , wherein said separating layer ( 5 ) comprises a polyethylene terephthalate barrier polymer.
59 . The solid transdermal therapeutic system as defined in claim 47 , wherein said UV absorber is colorless or yellow.
60 . The solid transdermal therapeutic system as defined in claim 47 , which is effective as a fertility controlling preparation.
61 . The solid transdermal therapeutic system as defined in claim 47 , wherein said backing layer comprises a polyethylene.
62 . The solid transdermal therapeutic system as defined in claim 25 , wherein the at least one active ingredient-containing matrix ( 2 ) and the adhesive layer ( 4 ) are self-adhesive and comprise at least one polyisobutylene polymer.
63 . The solid transdermal therapeutic system as defined in claim 25 , wherein said UV absorber is present in a concentration of from 0.5 to 2.5% (m/m) in dissolved form in the adhesive layer ( 4 ).