Multi-layer transdermal drug delivery system containing ibuprofen or structural analogue thereof
A multi-layer transdermal drug delivery system containing ibuprofen or a structural analogue thereof, comprising a transdermal patch containing ibuprofen or a structural analogue thereof and a second combined layer. The transdermal patch comprises a polymer matrix layer, the polymer matrix layer comprising an active ingredient, a compound containing at least one amino group, and a pressure-sensitive adhesive. All or some of active ingredient-amino compound salts or all or some of free active ingredients formed in the polymer matrix layer are kept in a uniform dissolution state in the polymer matrix, and can be stably stored before use, without recrystallization. The transdermal drug delivery system can continuously and controllably deliver a therapeutically effective amount of ibuprofen or a structural analogue thereof for 12 to 24 hours in the absence of a transdermal enhancer, has excellent wearing ability, and avoids a cold flow phenomenon.
1 . A transdermal patch containing ibuprofen, wherein the transdermal patch comprises a polymer matrix layer comprising:
an active ingredient,
a compound containing at least one amino group, wherein the compound containing at least one amino group is an unprotonated fatty amine,
a pressure-sensitive adhesive, and
a filler in an amount of from 0.5% to 10% by weight of the total dry polymer matrix, wherein the filler comprises colloidal silicon dioxide;
wherein the active ingredient is ibuprofen;
wherein in the polymer matrix layer, part of the active ingredient forms a salt with the unprotonated fatty amine; a molar ratio of the active ingredient in the polymer matrix layer to the amino group in the compound containing at least one amino group is 12:1 to 1:1; and a content by weight of the active ingredient in the polymer matrix layer is 15% to 45%.
2 . The transdermal patch according to claim 1 , wherein the fatty amine comprises one or more of ethanolamine, diethanolamine, triethanolamine, diethylamine, triethylamine, propane diamine, N-ethylmorpholine, N-ethylpiperidine, N-ethylpiperazine, N-hydroxyethylpiperidine, N-hydroxyethylpyrrole, dimethylpropanediamine, tetramethylpropanediamine, N-dodecylpyrrole, trihexylamine, N-dodecyl homopiperidine, pyridin-2-yl-methanol, ethylenediamine, tetramethyl ethylenediamine, spermidine, spermine, cyclen, 3-(piperazin-1-yl) propan-1,2-diol, N-hydroxyethylpiperazine, N-methylmorpholine, triethylenediamine, tris(2-aminoethyl)amine, 2-piperazinone, 3-aminopiperidine, 1,3-cyclohexanedimethylamine, propylene glycol bis(3-aminopropyl) ether, and ethylene glycol bis(3-aminoethyl) ether.
3 . The transdermal patch according to claim 2 , wherein
the melting point of the formed active ingredient-amino compound salt is lower than the melting point of ibuprofen.
4 . The transdermal patch according to claim 2 , wherein a surface area of the filler ranges from 1.5 m 2 /g to 15 m 2 /g.
5 . The transdermal patch according to claim 2 , wherein the polymer matrix layer does not contain a transdermal enhancer, wherein the transdermal enhancer is selected from the group consisting of propylene glycol, PEG600, olive oil, squalene, silicone oil, mineral oil, oleic acid, isopropyl myristate, cetyl palmitate, propylene glycol monocaprylate, caprylic/capric triglyceride, ethyl oleate, oleoyl polyoxyl-6 glyceride, urea, azone, N-methylpyrrolidone, dimethyl sulfoxide and glycerin.
6 . The transdermal patch according to claim 2 , wherein a molar ratio of the active ingredient in the polymer matrix layer to the amino group in the compound containing at least one amino group is 10:1 to 1.5:1; and/or,
a content by weight of the compound containing at least one amino group in the polymer matrix layer is 1% to 15%; and/or,
a content by weight of the active ingredient in the polymer matrix layer is 20% to 40%; and/or
a content by weight of the pressure-sensitive adhesive in the polymer matrix layer is 40% to 80%.
7 . The transdermal patch according to claim 2 , wherein the patch further comprises a backing layer and a protective layer; and the polymer matrix layer is located between the backing layer and the protective layer.
8 . The transdermal patch according to claim 1 , wherein
the melting point of the formed active ingredient-amino compound salt is lower than the melting point of ibuprofen.
9 . The transdermal patch according to claim 8 , wherein a surface area of the filler ranges from 1.5 m 2 /g to 15 m 2 /g.
10 . The transdermal patch according to claim 8 , wherein the polymer matrix layer does not contain a transdermal enhancer.
11 . The transdermal patch according to claim 8 , wherein a molar ratio of the active ingredient in the polymer matrix layer to the amino group in the compound containing at least one amino group is 10:1 to 1.5:1; and/or,
a content by weight of the compound containing at least one amino group in the polymer matrix layer is 1% to 15%; and/or,
a content by weight of the active ingredient in the polymer matrix layer is 20% to 40%; and/or,
a content by weight of the pressure-sensitive adhesive in the polymer matrix layer is 40% to 80%.
12 . The transdermal patch according to claim 1 , wherein a surface area of the filler ranges from 1.5 m 2 /g to 15 m 2 /g.
13 . The transdermal patch according to claim 12 , wherein the polymer matrix layer does not contain a transdermal enhancer.
14 . The transdermal patch according to claim 1 , wherein the polymer matrix layer does not contain a transdermal enhancer.
15 . The transdermal patch according to claim 1 , wherein a molar ratio of the active ingredient in the polymer matrix layer to the amino group in the compound containing at least one amino group is 10:1 to 1.5:1; and/or,
a content by weight of the compound containing at least one amino group in the polymer matrix layer is 1% to 15%; and/or,
a content by weight of the active ingredient in the polymer matrix layer is 20% to 40%; and/or,
a content by weight of the pressure-sensitive adhesive in the polymer matrix layer is 40% to 80%.
16 . The transdermal patch according to claim 1 , wherein the patch further comprises a backing layer and a protective layer; and the polymer matrix layer is located between the backing layer and the protective layer.
17 . A multi-layer transdermal drug delivery system containing ibuprofen, wherein the multi-layer transdermal drug delivery system comprises the transdermal patch according to claim 1 , and further comprises a second combined layer; the second combined layer comprises a backing layer, a protective layer, and a polymer matrix layer located between the backing layer and the protective layer; and the polymer matrix layer comprises a pressure-sensitive adhesive.
18 . The multi-layer transdermal drug delivery system according to claim 17 , wherein the polymer matrix layer of the second combined layer further comprises a pharmaceutically acceptable auxiliary material, and/or further comprises ibuprofen; and
a content by weight of ibuprofen in the polymer matrix layer of the second combined layer is ≤15%.
19 . The multi-layer transdermal drug delivery system according to claim 18 , wherein a peripheral width of the second combined layer is 0.5 cm to 1.0 cm wider than the peripheral width of the transdermal patch.
20 . The multi-layer transdermal drug delivery system according to claim 17 , wherein a peripheral width of the second combined layer is 0.5 cm to 1.0 cm wider than the peripheral width of the transdermal patch.