TRANSDERMAL DRUG DELIVERY SYSTEM CONTAINING DONEPEZIL
The present invention provides a transdermal drug delivery system comprising donepezil or its pharmaceutically acceptable salt and method of making the same.
1 . A transdermal drug delivery system comprising:
(a) donepezil or a pharmaceutically acceptable salt thereof as an active ingredient; and
(b) an acrylate-rubber hybrid adhesive,
wherein, the acrylate-rubber hybrid adhesive is prepared by a process without n-hexane.
2 . The transdermal drug delivery system of claim 1 , wherein the transdermal drug delivery system consists of a backing layer, the drug-containing matrix layer, and a release layer.
3 . The transdermal drug delivery system of claim 1 , wherein the acrylate-rubber hybrid is an acrylic polymer comprising a C 4 -C 18 alkyl acrylate monomer grafted with a rubber macromer having a glass transition temperature of not more than −30° C.
4 . The transdermal drug delivery system of claim 1 , wherein the acrylate-rubber hybrid adhesive is prepared by dissolving monomers in n-heptane, ethyl acetate, acetylacetone, or a mixture thereof, but without n-hexane.
5 . The transdermal drug delivery system of claim 1 , wherein the acrylate-rubber hybrid adhesive is prepared using ethyl acetate and n-haptane.
6 . The transdermal drug delivery system of claim 1 , wherein the acrylate-rubber hybrid adhesive is Duro-Tak™ 87-502B or Duro-Tak™ 87-504B.
7 . The transdermal drug delivery system of claim 1 , wherein the donepezil or its pharmaceutically acceptable salt is present in an amount ranging from 5 to 40% by weight, based on the total weight of the drug-containing matrix layer.
8 . The transdermal drug delivery system of claim 1 , wherein the acrylate-rubber hybrid is present in an amount ranging from 60 to 90% by weight, based on the total weight of the drug-containing matrix layer.
9 . The transdermal drug delivery system of claim 1 , further comprising an acrylate polymer or a methacrylate polymer as a crystallization-inhibiting agent.
10 . The transdermal drug delivery system of claim 9 , wherein the crystallization-inhibiting agent is present in an amount ranging from 1 to 10% by weight, based on the total weight of the drug-containing matrix layer.
11 . The transdermal drug delivery system of claim 9 , wherein the crystallization-inhibiting agent is a copolymer of butyl methacrylate, 2-dimethylaminoethyl methacrylate, and methyl methacrylate in a weight ratio of 1:2:1.
12 . The transdermal drug delivery system of claim 1 , further comprising one or more absorption enhancers selected from the group consisting of terpenes; surfactants; polyoxyethylene alkyl ethers; fatty alcohols; sugar esters; glycerols; alkyl 2-ethyl hexanates; and diethoxylethyl succinates.
13 . The transdermal drug delivery system of claim 10 , wherein the absorption enhancer is present in an amount ranging from 1 to 20% by weight, based on the total weight of the drug-containing matrix layer.
14 . The transdermal drug delivery system of claim 10 , wherein the absorption enhancer is one or more selected from the group consisting of polyethylene glycol palm kernel glyceride, polyoxyethylene lauryl ether, polyglyceryl-3 oleate, lauryl alcohol, and oleyl alcohol.
15 . A method of preparing the transdermal drug delivery system of claim 1 comprising:
(i) mixing donepezil with an acrylate-rubber hybrid adhesive;
(ii) adding a solvent to the mixture obtained from step (i);
(iii) casting the solution obtained from step (ii) on a release liner coated with silicone;
(iv) drying the casted mixture obtained from (iii);
(v) laminating a polyethylene film onto the dried layer obtained from step (iv) to form a backing membrane to prepare a transdermal drug delivery system.