Claims for Patent: 11,559,501

Summary for Patent: 11,559,501

Title:	Transdermal amphetamine compositions with low levels of carbamate
Abstract:	Described are methods for reducing the formation of amphetamine carbamate and amphetacarbamate in transdermal amphetamine compositions, compositions with low levels of amphetacarbamate, and methods using such compositions for transdermal delivery of amphetamine.
Inventor(s):	Atsushi Sonobe, Deboprosad Mondal, Naruhito Higo
Assignee:	Noven Pharmaceuticals Inc
Application Number:	US17/569,862
Patent Claims:	1. A transdermal amphetamine composition with reduced amphetammonium-amphetacarbamate content, comprising a drug-containing polymer matrix comprising a therapeutically effective amount of amphetamine in a pressure-sensitive adhesive polymer matrix, wherein the drug-containing polymer matrix has reduced amphetammonium-amphetacarbamate content, determined as an amphetacarbamate content of 0.5-5% w/w of the actual or target amphetamine content of the drug-containing polymer matrix, wherein the drug-containing polymer matrix is substantially free of visible crystals of amphetacarbamate. 2. The composition of claim 1, wherein, at the time of manufacture, the drug-containing polymer matrix has an amphetacarbamate content of no more than 3.0% w/w of the actual amphetamine. 3. The composition of claim 1, wherein at the time of manufacture, the drug-containing polymer matrix has an amphetacarbamate content of 0.5-5% w/w of the actual amphetamine content. 4. The composition of claim 1, wherein, at the time of manufacture, the drug-containing polymer matrix has an amphetacarbamate content of 0.5-5% of the target amphetamine content, and, after storage for six months at ambient conditions in a sealed pouch that is substantially impervious to carbon dioxide, the drug-containing polymer matrix has an amphetacarbamate content of no more than 5.0% of the target amphetamine content. 5. The composition of claim 1, wherein the drug-containing polymer matrix has a target amphetamine content or actual amphetamine content at the time of manufacture of 5-20% w/w dry. 6. The composition of claim 1, wherein the drug-containing polymer matrix has a target amphetamine content or actual amphetamine content at the time of manufacture of 15% w/w dry. 7. The composition of claim 1, wherein the amphetamine is d-amphetamine. 8. The composition of claim 1, wherein the drug-containing polymer matrix has a shear adhesion less than that of a comparator drug-containing polymer matrix layer having the same polymer matrix components but a higher amphetacarbamate content, when assessed by the same shear adhesion test. 9. The composition of claim 1, wherein the drug-containing polymer matrix has a peel force greater than that of a comparator drug-containing polymer matrix layer having the same polymer matrix components but a higher amphetacarbamate content, when assessed by the same peel adhesion test. 10. The composition of claim 1, wherein the pressure-sensitive adhesive polymer component of the drug-containing polymer matrix consists of one or more non-functional acrylic polymers free of vinyl acetate moieties. 11. The composition of claim 1, wherein the pressure-sensitive adhesive polymer component of the drug-containing polymer matrix consists of one or more non-functional acrylic polymers free of vinyl acetate moieties, including at least one acrylic polymer polymerized from monomers that include both (i) a soft acrylic monomer having a glass transition temperature (Tg) from −70° C. to −10° C. in an amount from 20-70% by weight of the polymer; and (ii) a hard acrylic monomer having a Tg from −5° C. to 120° C. in an amount from 30-80% by weight of the polymer. 12. The composition of claim 11, wherein: (i) the soft acrylic monomer is one or more selected from 2-ethyl hexyl acrylate, isobutyl acrylate, ethyl acrylate, butyl acrylate, dodecyl methacrylate, 2 ethylhexyl methacrylate, 2-ethoxyethyl acrylate, isopropyl acrylate, and 2 methoxyethyl acrylate, and (ii) the hard acrylic monomer is one or more selected from methacrylate, N-butyl acrylate, acrylic acid, butyl methacrylate, ethyl methacrylate, methyl methacrylate, hexyl methacrylate, and methyl acrylate. 13. The composition of claim 12, wherein the pressure-sensitive adhesive polymer component of the drug-containing polymer matrix consists of one or more of non-functional acrylic polymers free of vinyl acetate moieties polymerized from monomers that consist of both monomers selected from said soft acrylic monomers (i) and monomers selected from said hard acrylic monomers (ii). 14. An amphetamine transdermal drug delivery system comprising a transdermal amphetamine composition according to claim 1 and a backing layer. 15. The composition of claim 1, wherein the drug-containing polymer matrix has an amphetacarbamate content of 0.5-5% w/w of the actual amphetamine content of the drug-containing polymer matrix. 16. The composition of claim 1, wherein the drug-containing polymer matrix has an amphetacarbamate content of 0.5-5% w/w of the target amphetamine content of the drug-containing polymer matrix. 17. The composition of claim 1, wherein at the time of manufacture, the drug-containing polymer matrix has an amphetacarbamate content of 0.5-5% w/w of the target amphetamine content. 18. The composition of claim 1, wherein, at the time of manufacture, the drug-containing polymer matrix has an amphetacarbamate content of no more than 3.0% w/w of the target amphetamine content. 19. The composition of claim 1, wherein the drug-containing polymer matrix has an amphetacarbamate content of no more than 3.0% w/w of the target amphetamine content. 20. The composition of claim 1, wherein the drug-containing polymer matrix has an amphetacarbamate content of no more than 3.0% w/w of the actual amphetamine content. 21. The composition of claim 1, wherein the amphetamine is 1-amphetamine.