Transdermal therapeutic system comprising buprenorphine
The invention is concerned with a transdermal therapeutic system (TTS) comprising buprenorphine and a method of manufacturing such a TTS. The transdermal therapeutic system is used for the transdermal administration of buprenorphine and analogues thereof. In particular, the invention relates to the use of a transdermal therapeutic system (TTS) for analgesic purposes. The TTS according to the invention comprises a transdermal drug delivery composition comprising buprenorphine and an adhesive component, which is a mixture of a crosslinked and a non-crosslinked acrylic polymer and a penetration enhancer comprising a keto acid.
1. A transdermal therapeutic system comprising:
1) a backing layer,
2) at least one drug containing adhesive layer containing a transdermal drug delivery composition consisting of:
i. 5 to 15% by weight of buprenorphine, based on the total weight of the composition,
ii. an adhesive component, which preferably forms an amorphous mass, comprising 20 to 50% by weight of a crosslinked acrylic polymer and 5 to 25% by weight of a non-crosslinked acrylic polymer, based on the total weight of the composition, in a ratio of 80 to 20 parts by weight to 60 to 40 parts by weight,
iii. and 5 to 15% by weight of levulinic acid, based on the total weight of the composition,
iv. 10 to 20% by weight of oleyl oleate, based on the total weight of the composition, and
v. 5 to 15% by weight of polyvinyl pyrrolidone, based on the total weight of the composition; and
3) optionally at least one further adhesive layer, and
4) further optionally, a release liner,
wherein the crosslinked acrylic polymer is obtained from one or more non-functional monomers and one or more functional monomers, the functional monomer comprising a carboxy group, an epoxy group and/or a hydroxy group,
wherein the transdermal therapeutic system releases buprenorphine in an amount sufficient to achieve a constant blood plasma of at least 200 pg/ml for up to 4 days.
2. The transdermal therapeutic system according to claim 1 , wherein the functional monomer is selected from the group consisting of acrylic acid, methacrylic acid, (meth)acrylic acid hydroxy alkylester, 2-hydro-xylethyl acrylate and glycidyl methacrylate.
3. The transdermal therapeutic system according to claim 1 , wherein the non-crosslinked acrylic polymer is obtained from monomers comprising one or more (meth)acrylic acid alkyl esters, optionally one or more of a n-alkyl acrylamide, and further optionally one or more of a vinyl ester, or mixtures thereof.
4. The transdermal therapeutic system according to claim 3 , wherein:
the (meth)acrylic acid alkyl ester is selected from the group consisting of 2-ethylhexyl acrylate, butyl acrylate, methyl acrylate and methyl methacrylate,
the monomers further comprise an n-alkylacrylamide comprising t-octyl acrylamide, and
the monomers further comprise a vinyl ester comprising vinyl acrylate.
5. The transdermal therapeutic system according to claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of 78:22 to 65:35 parts by weight.
6. The transdermal therapeutic system according to claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of 76:24 to 67:33 parts by weight.
7. The transdermal therapeutic system according to claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of about 70:30 parts by weight.