Claims for Patent: 11,590,228

Summary for Patent: 11,590,228

Title:	Extended release amphetamine compositions
Abstract:	An oral amphetamine extended release liquid suspension is described. The compositions contain a combination of an uncoated amphetamine-cation exchange resin complex, a barrier coated amphetamine-cation exchange resin complex-matrix, and an uncomplexed amphetamine, wherein one or more of these components contains blends of different forms of amphetamines. Either the modified release coated and/or the uncoated amphetamine-cation exchange resin complex may have two forms of amphetamine in a complex with a single cation exchange resin. Following administration of a single dose of the composition, a therapeutically effective amount of amphetamine is reached by about one hour and the composition provides at least a thirteen hour effect post-dose.
Inventor(s):	Ketan Mehta, Kalyan Kathala, Yu-Hsing Tu
Assignee:	PROVIDENT BANK
Application Number:	US16/376,638
Patent Claims:	1. An orally administrable extended release amphetamine liquid suspension comprising: (A) at least one modified release component comprising an amphetamine-cation exchange resin complex-optional matrix, wherein the amphetamine-cation exchange resin complex comprises (i) two or more amphetamines both bound to the same cation exchange resin or each bound to a different cation exchange resins, wherein when the optional matrix is present, the amphetamine-cation exchange resin complex-matrix further comprises a hydrophilic polymer or copolymer or a hydrophobic polymer and (ii) a water-insoluble, water-permeable, pH-independent barrier coating which provides a sustained or extended release to the two or more amphetamines, wherein the two or more amphetamines are at least a d-amphetamine and an l-amphetamine, wherein the d-amphetamine and the l-amphetamine are provided by d-amphetamine and at least one of (d,l)-amphetamine and l-amphetamine; (B) a first immediate release amphetamine component which comprises d-amphetamine or a pharmaceutically acceptable salt thereof, and l-amphetamine or a pharmaceutically acceptable salt thereof, or mixtures thereof, wherein the d- and l-amphetamine are provided by d-amphetamine and at least one of (d, l)-amphetamine and l-amphetamine; and (C) a second immediate release amphetamine component which comprises an amphetamine-cation exchange resin complex in an optional matrix, wherein the amphetamine-cation exchange resin complex-optional matrix comprises at least a d-amphetamine and an l-amphetamine both bound to the same cation exchange resin or each bound to different cation exchange resins, wherein the d-amphetamine and the l-amphetamine are provided by d-amphetamine and at least one of (d, l)-amphetamine or l-amphetamine; wherein none of the amphetamine components in the suspension has a delay release coating which delays the release of the amphetamines, wherein the suspension provides at least one immediate release profile for d-amphetamine and for l-amphetamine and a therapeutic profile for at least 13 hours for d-amphetamine and for l-amphetamine; and wherein the suspension comprises a ratio of about 3 parts by weight d-amphetamine to about 1 part by weight l-amphetamine. 2. The orally administrable extended release amphetamine suspension according to claim 1, wherein following a single dose of the suspension in a pediatric patient 6 to 12 years of age, the suspension provides a pharmacokinetic profile for d-amphetamine and l-amphetamine of: geometric mean plasma AUC0-∞ of about 910 h*ng/mL to about 1115 h*ng/mL for d-amphetamine and about 245 h*ng/mL to about 400 h*ng/mL for 1-amphetamine and a geometric mean plasma Cmax of about 45 ng/mL to about 60 ng/mL for d-amphetamine and about 14 ng/mL to about 18 ng/mL for 1-amphetamine. 3. The orally administrable extended release amphetamine suspension according to claim 2, wherein the geometric mean plasma AUC0-∞ for d-amphetamine is about 950 h*ng/mL to about 1050 h*ng/mL for d-amphetamine and about 300 h*ng/mL to about 375 h*ng/mL for l-amphetamine and a geometric mean plasma Cmax of about 50 ng/mL to about 55 ng/mL for d-amphetamine and about 15 ng/mL to about 17 ng/mL for l-amphetamine. 4. The orally administrable extended release amphetamine suspension according to claim 2, wherein the geometric mean plasma AUC0-∞ for d-amphetamine is about 1013 h*ng/mL for d-amphetamine and for l-amphetamine is about 363 h*ng/mL and the geometric mean plasma Cmax for d-amphetamine is about 53 ng/mL and for l-amphetamine is about 16 ng/mL. 5. The orally administrable extended release suspension according to claim 1, wherein the suspension contains two different amphetamine counterions. 6. The orally administrable extended release suspension according to claim 5, wherein the two different counterions are aspartate and sulfate. 7. The orally administrable extended release suspension according to claim 6, wherein the aspartate counterions are present in a concentration of about 0.01% w/v to up to 0.05% w/v. 8. The orally administrable extended release suspension according to claim 6, wherein the sulfate counterions are present in a concentration of about 0.01% w/v to up to 0.05% w/v. 9. The orally administrable extended release aqueous liquid suspension according to claim 1, which comprises 20 mg total amphetamines per 8 mL, wherein the weight of total amphetamines is determined on the basis of amphetamine base in the amphetamine components. 10. A method for treating a patient having attention deficit hyperactivity disorder, said method comprising delivering to the patient an orally administrable extended release suspension according to claim 1. 11. The method according to claim 10, wherein the therapeutic effect lasts up to about 18 hours following post-dose administration to a patient. 12. The method according to claim 10, wherein following a single dose of the suspension in a pediatric patient 6 to 12 years of age, the suspension provides a pharmacokinetic profile for d-amphetamine and l-amphetamine of: geometric mean plasma AUC0-∞ of about 910 h*ng/mL to about 1115 h*ng/mL for d-amphetamine and about 245 h*ng/mL to about 400 h*ng/mL for 1-amphetamine and a geometric mean plasma Cmax of about 45 ng/mL to about 60 ng/mL for d-amphetamine and about 14 ng/mL to about 18 ng/mL for 1-amphetamine. 13. The method according to claim 10, wherein following a single dose of the suspension in a pediatric patient 6 to 12 years of age, the suspension provides a pharmacokinetic profile for d-amphetamine and l-amphetamine of: (a) geometric mean plasma AUC0-∞ for d-amphetamine is about 950 h*ng/mL to about 1050 h*ng/mL for d-amphetamine and about 300 h*ng/mL to about 375 h*ng/mL for 1-amphetamine and a geometric mean plasma Cmax of about 50 ng/mL to about 55 ng/mL for d-amphetamine and about 15 ng/mL to about 17 ng/mL for 1-amphetamine, and/or (b) geometric mean plasma AUC0-∞ for d-amphetamine is about 1013 h*ng/mL for d-amphetamine and for 1-amphetamine is about 363 h*ng/mL and the geometric mean plasma Cmax for d-amphetamine is about 53 ng/mL and for 1-amphetamine is about 16 ng/mL. 14. An orally administrable extended release amphetamine liquid suspension comprising: (A) at least one modified release component comprising an amphetamine-cation exchange resin complex-optional matrix, wherein the amphetamine-cation exchange resin complex comprises (i) two or more amphetamines both bound to the same cation exchange resin, wherein when the optional matrix is present, the amphetamine-cation exchange resin complex-matrix further comprises a hydrophilic polymer or copolymer or a hydrophobic polymer and (ii) a water-insoluble, water-permeable, pH-independent, barrier coating which provides a sustained or extended release to the two or more amphetamines, wherein the two or more amphetamines of (i) are at least a d-amphetamine and an l-amphetamine, wherein the d-amphetamine and the l-amphetamine are provided by d-amphetamine and at least one of (d,l)-amphetamine and l-amphetamine; (B) a first immediate release amphetamine component which comprises d-amphetamine or a pharmaceutically acceptable salt thereof, and l-amphetamine or a pharmaceutically acceptable salt thereof, or mixtures thereof, wherein the d- and l-amphetamine are provided by d-amphetamine and at least one of (d, l)-amphetamine and l-amphetamine; and (C) a second immediate release amphetamine component which comprises an amphetamine-cation exchange resin complex in an optional matrix, wherein the amphetamine-cation exchange resin complex-optional matrix comprises at least a d-amphetamine and an l-amphetamine both bound to the same cation exchange resin, wherein the d-amphetamine and the l-amphetamine are provided by d-amphetamine and at least one of (d, l)-amphetamine or l-amphetamine; wherein none of the amphetamine components in the suspension has a delay release coating which delays the release of the amphetamines, wherein based on the weight of the total amphetamines as calculated on the basis of the free base amphetamines, the modified release component (A) comprises 45% to 75% by weight of the total amphetamines in the suspension, the immediate release component (B) comprises 5% to 25% by weight of the total amphetamines in the suspension, and immediate release (C) comprises 30% to 40% by weight of the total amphetamines in the suspension; and wherein the suspension provides at least one immediate release profile for d-amphetamine and for l-amphetamine and a therapeutic profile for at least 13 hours for d-amphetamine and for l-amphetamine; wherein the suspension comprises a ratio of about 3 parts by weight d-A amphetamine to about 1 part by weight l-amphetamine. 15. The orally administrable extended release suspension according to claim 14, wherein the modified release component (A) comprises at least 55% of the total amphetamines and the second immediate release component (C) comprises at least 35% of the total amphetamines. 16. The orally administrable extended release suspension according to claim 14, wherein the water-insoluble, water-permeable, barrier coating of (A) comprises: (a) a cured, water-permeable, non-ionic, pH-independent barrier coating comprising polyvinylacetate, a stabilizer, and a plasticizer; (b) an ionic, pH-independent, acrylic based coating comprising a polymer or copolymer comprising ethyl acrylate and methyl methacrylate applied as an aqueous dispersion; or (c) a solvent-based ethylcellulose, optionally with a plasticizer. 17. The orally administrable extended release aqueous liquid suspension according to claim 16, wherein the barrier coating is a cured, water-insoluble, water-permeable, non-ionic, pH-independent barrier coating comprising about 70 to about 90% w/w polyvinylacetate, a stabilizer, and about 2 to about 10% w/w of a plasticizer. 18. A method for treating a patient having attention deficit hyperactivity disorder, said method comprising delivering to the patient an orally administrable extended release suspension according to claim 14.