Silicone-containing acrylic polymers for transdermal drug delivery compositions

Abstract

Described herein are silicone-containing acrylic polymers useful, for example, in transdermal drug delivery compositions, to methods of making and using them, to transdermal drug delivery compositions comprising them, and to methods of making and using such transdermal drug delivery compositions. The polymers are particular suitable for formulating amine drugs, such as amphetamine, methylphenidate, rivastigmine, paroxetine and clonidine.

What is claimed is: 
     
         1 . A composition for the transdermal delivery of an amine drug in the form of a flexible finite system for topical application, comprising a polymer matrix comprising a drug and a silicone-containing acrylic polymer. 
     
     
         2 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is a non-reactive silicone-containing acrylic polymer made from one or more non-reactive acrylic monomers and one or more non-reactive silicone-containing acrylic monomers, wherein the non-reactive monomers and polymer do not react with amine groups of the amine drug. 
     
     
         3 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is made from one or more non-reactive acrylic monomers selected from the group consisting of methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, hexyl acrylate, hexyl methacrylate, 2-ethylbutyl acrylate, 2-ethylbutyl methacrylate, isooctyl acrylate, isooctyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decyl acrylate, decyl methacrylate, dodecyl acrylate, dodecyl methacrylate, tridecyl acrylate, tridecyl methacrylate, octyl acrylamide, hydroxyethyl acrylate, and vinyl pyrrolidone, vinyl acetate, and one or more non-reactive silicone-containing acrylic monomers, wherein the non-reactive monomers do not react with amine groups of the amine drug. 
     
     
         4 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is made from (i) one or more acrylic monomers selected from the group consisting of methyl acrylate monomers, methyl methacrylate monomers, 2-ethylhexyl acrylate monomers, butyl acrylate monomers, amide-containing monomers and vinyl-group containing monomers, and (ii) one or more non-reactive silicone-containing acrylic monomers, wherein the non-reactive monomers do not react with amine groups of the amine drug. 
     
     
         5 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is made from (i) up to four types of acrylic monomers selected from the group consisting of (1) methyl acrylate and methyl methacrylate monomers; (2) 2-ethylhexyl acrylate and butyl acrylate monomers, (3) amide-containing monomers, and (4) vinyl group-containing monomers, and one or more non-reactive silicone-containing acrylic monomers, wherein the non-reactive monomers do not react with amine groups of the amine drug. 
     
     
         6 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is made from one or more silicone-containing acrylic monomers selected from the group consisting of siloxy silanes and polydimethylsiloxanes, and one or more acrylic monomers. 
     
     
         7 . The composition of  claim 1 , wherein the silicone-containing acrylic polymer is made from one or more non-reactive silicone-containing acrylic monomers selected from the group consisting of 3-acryloxypropyl tri(trimethylsiloxy)silane, 3-methacryloxypropyl tri(trimethylsiloxy)silane, and mono-vinyl terminated polydimethylsiloxane, and one or more non-reactive acrylic monomers, wherein the non-reactive monomers do not react with amine groups of the amine drug. 
     
     
         8 . The composition of  claim 1 , wherein the drug is an amine drug selected from the group consisting of amphetamine, methylphenidate, rivastigmine, rotigotine, fentanyl, paroxetine clonidine, amiodarone, amitriptyline, atropine, benztropine, biperiden, bornaprine, bupivacaine, chlorpheniramine, cinnarizine, clomipramine, cyclopentolate, darifenacin, dexetimide, dicyclomine, diltiazem, diphenhydramine, doxepin, ethopropazine, flavoxate, homatropine, imipramine, loxapine, mazaticol, metixene, oxybutin, oxyphencyclimine, phenglutarimide, physostigmine, piperidolate, pirenzepine, procyclidine, profenamine, propiverine, scopolamine, telenzepine, theophylline, tolterodine, trimipramine, trihexyphenidyl, tropatepine, and tropicamide. 
     
     
         9 . The composition of  claim 1 , wherein the drug is an amine drug selected from the group consisting of amphetamine, methylphenidate, rivastigmine, paroxetine and clonidine. 
     
     
         10 . The composition of  claim 1 , further comprising a backing. 
     
     
         11 . The composition according to  claim 10 , further comprising a release liner. 
     
     
         12 . A method for the transdermal delivery of an amine drug, comprising topically applying a composition as claimed in  claim 1  to the skin or mucosa of a subject in need thereof. 
     
     
         13 . A method of manufacturing a composition for the transdermal delivery of an amine drug in the form of a flexible finite system for topical application, comprising forming a polymer matrix blend by blending an amine drug and a silicone-containing acrylic polymer in a solvent, applying the polymer matrix blend to a support layer, and removing any remaining solvent. 
     
     
         14 . A method of manufacturing a silicone-containing acrylic polymer, comprising copolymerizing acrylic monomers with silicone-containing acrylic monomers. 
     
     
         15 . The method of  claim 14 , wherein the acrylic monomers and silicone-containing acrylic monomers are non-reactive with amine groups. 
     
     
         16 . The method of  claim 14 , wherein the silicone-containing acrylic polymer is comprised of 1-99% by weight acrylic monomers and 99-1% by weight silicone-containing acrylic monomers, based on the total dry weight of the polymer. 
     
     
         17 . The method of  claim 16 , wherein the silicone-containing acrylic polymer is comprised of up to 50% by weight acrylic monomers and at least 50% by weight silicone-containing acrylic monomers, based on the total dry weight of the polymer. 
     
     
         18 . The method of  claim 16 , wherein the silicone-containing acrylic polymer is comprised of at least 50% by weight acrylic monomers and up to 50% by weight silicone-containing acrylic monomers, based on the total dry weight of the polymer. 
     
     
         19 . Use of a silicone-containing acrylic polymer in the preparation of a medicament for the transdermal delivery of an amine drug. 
     
     
         20 . Compositions in the form of a flexible finite system for topical application, comprising a polymer matrix comprising a drug and a silicone-containing acrylic polymer, for use in the transdermal delivery of an amine drug.