Compositions and methods for transdermal delivery of amphetamine

Abstract

Compositions for the transdermal delivery of amphetamine in a flexible, finite form are described. The compositions comprise a polymer matrix that includes amphetamine or a pharmaceutically acceptable salt or prodrug thereof and a backing layer comprising a polyurethane film layer and a polyester film layer, with a polyurethane adhesive disposed therebetween. Related methods also are described. Also described are compositions that exhibit a short onset period and a long duration of therapeutic effect

1 .- 25 . (canceled) 
     
     
         26 . A composition for the transdermal delivery of amphetamine in the form of a flexible finite system for topical application, made by a process comprising combining (i) a polymer matrix comprising amphetamine or a pharmaceutically acceptable salt or prodrug thereof and (ii) a backing layer comprising (a) a polyurethane film layer and (b) a polyester film layer, wherein a polyurethane adhesive is disposed between the polyurethane film layer and the polyester film layer, such that the polyurethane film layer of the backing layer is adjacent the polymer matrix. 
     
     
         27 . The composition of  claim 26 , wherein the polyurethane film layer is comprised of a polyether aromatic polyurethane polymer. 
     
     
         28 . The composition of  claim 26 , wherein the polyurethane film layer has a thickness of about 1.5 mils. 
     
     
         29 . The composition of  claim 26 , wherein the polyester film layer has a thickness of from about 0.4 mils to 0.6 mils. 
     
     
         30 . The composition of  claim 26 , wherein the amphetamine is d-amphetamine free base. 
     
     
         31 . The composition of  claim 26 , wherein the polymer matrix comprises at least one acrylic polymer. 
     
     
         32 . The composition of  claim 26 , wherein the polymer matrix comprises at least one non acid-functional acrylic polymer. 
     
     
         33 . The composition of  claim 32 , wherein at least one non acid-functional acrylic polymer includes methacrylate and 2-ethylhexyl acrylate monomers and, optionally, methyl methacrylate monomers. 
     
     
         34 . The composition of  claim 32 , wherein at least one non acid-functional acrylic polymer includes methacrylate, 2-ethylhexyl acrylate, and amide group-containing monomers, and, optionally, methyl methacrylate monomers. 
     
     
         35 . The composition of  claim 26 , wherein the polymer matrix comprises about 10-20% by weight amphetamine or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         36 . The composition of  claim 26 , wherein the polymer matrix comprises (a) first non acid-functional acrylic polymer that includes 50% methacrylate monomers and 50% 2-ethylhexyl acrylate monomers, based on the weight of the first acrylic polymer; (b) a second non acid-functional acrylic polymer that includes methacrylate monomers, 2-ethylhexyl acrylate monomers, and amide group-containing monomers, and (c) about 10-20% by weight amphetamine or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         37 . The composition of  claim 36 , wherein the polymer matrix consists of 67.5% by weight of said first non acid-functional acrylic polymer, 17.5% by weight of said second non acid-functional acrylic polymer, and 15% by weight amphetamine, based on the total dry weight of the polymer matrix. 
     
     
         38 . The composition of  claim 26 , wherein the polymer matrix has a coat weight of about 6-8 mg/cm 2 , based on the active surface area of the polymer matrix. 
     
     
         39 . The composition of  claim 26 , wherein the composition comprises about 1 mg/cm 2  amphetamine. 
     
     
         40 . The composition of  claim 26 , wherein the flexible, finite system has a size of from about 2 cm 2  to about 60 cm 2 . 
     
     
         41 . The composition of  claim 26 , wherein the method further comprises providing a release liner on a face of the polymer matrix not adjacent the backing layer. 
     
     
         42 . The composition of  claim 26 , wherein the composition delivers amphetamine over a period of time of about 8-10 hours. 
     
     
         43 . The composition of  claim 26 , wherein the composition exhibits an onset period of from about 30 minutes to about 90 minutes. 
     
     
         44 . The composition of  claim 26 , wherein the composition exhibits a duration of therapeutic effect of at least about 12 hours from the time of application of the composition, when it is removed at about 9 hours after application. 
     
     
         45 . The composition of  claim 26 , wherein the composition exhibits a drug depletion of at least about 85% to about 93% at about 8 to 10 hours after application. 
     
     
         46 . A composition for the transdermal delivery of amphetamine in the form of a flexible finite system for topical application, made by a method comprising
 (i) applying to a release liner a polymer matrix comprising amphetamine or a pharmaceutically acceptable salt or prodrug thereof and drying the polymer matrix, and   (ii) applying to the polymer matrix a backing layer comprising (a) a polyurethane film layer and (b) a polyester film layer, wherein a polyurethane adhesive is disposed between the polyurethane film layer and the polyester film layer, such that the polyurethane film layer of the backing layer is adjacent the polymer matrix.