Claims for Patent: 9,456,993

Summary for Patent: 9,456,993

Title:	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.
Inventor(s):	Lambert; Robert L. (Miami, FL)
Assignee:	NOVEN PHARMACEUTICALS, INC. (Miami, FL)
Application Number:	14/585,964
Patent Claims:	1. A composition for the transdermal delivery of amphetamine in the form of a flexible finite system for topical application, comprising (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, wherein the polyurethane film layer of the backing layer is adjacent the polymer matrix, and wherein the polyurethane adhesive of the backing layer is selected from the group consisting of isocyanate-terminated polyether urethanes and isocyanate-terminated polyester urethanes, which optionally may be cured or part of a two-component adhesive. 2. The composition of claim 1, wherein the polyurethane film layer is comprised of a polyether aromatic polyurethane polymer. 3. The composition of claim 1, wherein the polyurethane film layer has a thickness of about 1.5 mils. 4. The composition of any claim 1, wherein the polyester film layer has a thickness of from about 0.4 mils to 0.6 mils. 5. The composition of claim 1, wherein the polyurethane adhesive of the backing layer is selected from the group consisting of isocyanate-terminated polyether urethanes and isocyanate-terminated polyester urethanes, which optionally may be cured. 6. The composition of claim 1, wherein the polyurethane adhesive of the backing layer is an isocyanate-terminated polyether urethane, which optionally may be cured with a curing agent. 7. The composition of claim 1, wherein the polyurethane adhesive of the backing layer is an isocyanate-terminated polyester urethane, which optionally may be cured with a curing agent. 8. The composition of claim 1, wherein the amphetamine is d-amphetamine free base. 9. The composition of claim 1, wherein the polymer matrix comprises at least one acrylic polymer. 10. The composition of claim 1, wherein the polymer matrix comprises at least one non acid-functional acrylic polymer. 11. The composition as claimed in claim 10, wherein at least one non acid-functional acrylic polymer includes methyl acrylate and 2-ethylhexyl acrylate monomers and, optionally, methyl methacrylate monomers. 12. The composition as claimed in claim 10, wherein at least one non acid-functional acrylic polymer includes methyl acrylate, 2-ethylhexyl acrylate, butyl acrylate, and amide group-containing monomers, and, optionally, methyl methacrylate monomers. 13. The composition of claim 1, wherein the polymer matrix comprises about 10 20% by weight amphetamine or a pharmaceutically acceptable salt or prodrug thereof. 14. The composition as claimed in claim 1, wherein the polymer matrix comprises (a) first non acid-functional acrylic polymer that includes 50% methyl acrylate 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 methyl acrylate monomers, 2-ethylhexyl acrylate monomers, butyl acrylate monomers, and amide group-containing monomers, and (c) about 10 20% by weight amphetamine or a pharmaceutically acceptable salt or prodrug thereof. 15. The composition as claimed in claim 13, 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. 16. The composition of claim 1, wherein the polymer matrix has a coat weight of about 6-8 mg/cm2, based on the active surface area of the polymer matrix. 17. The composition as claimed in claim 1, wherein the composition comprises about 1 mg/cm2 amphetamine. 18. The composition as claimed in claim 1, wherein the flexible, finite system has a size of from about 2 cm2 to about 60 cm2. 19. The composition as claimed in claim 1, further comprising a release liner. 20. The composition as claimed in claim 1, wherein the composition delivers amphetamine over a period of time of about 8-10 hours. 21. The composition as claimed in claim 1, wherein the composition exhibits an onset period of from about 30 minutes to about 90 minutes. 22. The composition as claimed in claim 1, 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. 23. The composition as claimed in claim 1, wherein the composition exhibits a drug depletion of at least about 85% to about 93% at about 8 to 10 hours after application. 24. The composition as claimed in claim 1, wherein the composition is stable against the formation of degradants. 25. The composition as claimed in claim 1, wherein the composition exhibits, after storage at 40.degree. C. for 3.5 months, the formation of at most up to about 1.0% w/w degradants, based on the total weight of amphetamine or pharmaceutically acceptable salt or prodrug thereof formulated in the composition. 26. A method of stimulating the central nervous system, treating attention deficit disorder (ADD), treating attention deficit hyperactivity disorder (ADHD), or treating narcolepsy, comprising administering a composition according to claim 1 to a subject in need thereof. 27. The composition of claim 1, wherein the polyurethane adhesive of the backing layer is cured by moisture or a curing agent. 28. The composition of claim 1, wherein the polyurethane adhesive of the backing layer further comprises a coreactant. 29. The composition of claim 1, wherein the polyurethane adhesive of the backing layer is applied at a thickness of from about 0.1 mils to about 1.0 mils.