Claims for Patent: 9,839,619

Summary for Patent: 9,839,619

Title:	Method for treating ADD or ADHD comprising administering amphetamine complexed with ion-exchange resin particles
Abstract:	The invention relates to dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms.
Inventor(s):	Tengler Mark, McMahen Russell
Assignee:	NEOS THERAPEUTICS, LP
Application Number:	US13844555
Patent Claims:	2. The method of claim 1 , wherein the second plurality of drug-resin particles comprises a triggered-release coating triggered by a pH change.3. The method of claim 2 , wherein the triggered-release coating is cellulose acetate phthalate claim 2 , cellulose acetate trimellitate claim 2 , hydroxypropyl methylcellulose phthalate claim 2 , polyvinyl acetate phthalate claim 2 , carboxymethylethylcellulose claim 2 , co-polymerized methacrylic acid/methacrylic acid methyl esters claim 2 , co-polymerized methacrylic acid/acrylic acid ethyl esters claim 2 , or mixtures thereof.4. The method of claim 1 , wherein the resin particles are strong acidic cation exchange resins claim 1 , selected from the group consisting of polistirex claim 1 , polacrilex claim 1 , cholestyramine claim 1 , polacrilin or mixtures thereof.5. The method of claim 1 , wherein 40%-50% of said ADHD effective agent is present in said first plurality of drug-resin particles and 50-60% of said ADHD effective agent is present in said second plurality of drug-resin particles.6. The method of claim 5 , wherein about 45% of said ADHD effective agent is present in said first plurality of drug-resin particles and about 55% of said ADHD effective agent is present in said second plurality of drug-resin particles.7. The method of claim 1 , wherein said pharmaceutical composition is a liquid suspension claim 1 , chewable composition claim 1 , or an orally disintegrating tablet composition.8. The method of claim 1 , wherein said drug-resin particles comprise 25% l-amphetamine and 75% d-amphetamine.9. The method of claim 1 , wherein the amount of drug delivered to said subject by said pharmaceutical composition is about 5 mg/24 hours to about 30 mg/24 hours.10. The method of claim 1 , wherein the amount of said ADHD effective agent delivered is 0.25 mg/kg subject/day to 1.5 mg/kg subject/day.11. The method of claim 1 , wherein said pharmaceutical composition is characterized by a dissolution profile in an in vitro dissolution assay wherein 40-45% of the ADHD effective agent is released within the first 45 minutes after the drug-resin particles are introduced into an in vitro dissolution assay claim 1 , followed by a period of substantially no ADHD effective agent release from 45 minutes to 2 hours claim 1 , and concluding with period of from 2 to 8 hours during which substantially all of the remaining ADHD effective agent is released claim 1 , wherein the conditions of the dissolution assay are an initial dissolution medium of 0.1 N HCl claim 1 , and after 2 hours claim 1 , the medium is adjusted to a pH of about 6.8; and the dissolution assay is performed using a USP Apparatus 2.12. The method of claim 1 , wherein the delayed release coating releases substantially all of the ADHD effective agent in the second plurality of drug-resin particles within about 60 minutes after initiation of the delayed release.13. The method of claim 1 , wherein said pharmaceutical composition is sufficient to maintain a therapeutically effective level of said ADHD effective agent in the subject over the course of at least 8 hours without further administration of ADHD effective agent.14. The method of claim 1 , wherein the amount of ADHD effective agent is equivalent to the amount of ADHD effective agent present in 5 mg claim 1 , 10 mg claim 1 , 15 mg claim 1 , 20 mg claim 1 , 25 mg claim 1 , or 30 mg of a reference composition without resin particles which comprises a mixture of dextroamphetamine sulfate claim 1 , dextroamphetamine saccharate claim 1 , amphetamine aspartate claim 1 , and amphetamine sulfate.15. The method of claim 1 , wherein one or more in vivo pharmacokinetic parameters of said pharmaceutical composition selected from the group consisting of C claim 1 , AUC claim 1 , AUC claim 1 , AUC claim 1 , AUC claim 1 , AUC claim 1 , AUC claim 1 , AUC claim 1 , and AUC have a 90% confidence interval with upper and lower bounds within a range from 90%415% of the value of the same parameter(s) for a bioequivalent reference composition.16. The method of claim 1 , wherein 20%-50% of said ADHD effective agent is present in said first plurality of drug-resin particles and 50-80% of said ADHD effective agent is present in said second plurality of drug-resin particles.17. The method of claim 1 , wherein varying concentrations of ethanol up to 40% do not significantly alter the rate and extent of absorption of amphetamine in said subject.18. The method of claim 17 , wherein the second plurality of drug-resin particles comprises a triggered-release coating triggered by a pH change.19. The method of claim 18 , wherein the triggered-release coating is cellulose acetate phthalate claim 18 , cellulose acetate trimellitate claim 18 , hydroxypropyl methylcellulose phthalate claim 18 , polyvinyl acetate phthalate claim 18 , carboxymethylethylcellulose claim 18 , co-polymerized methacrylic acid/methacrylic acid methyl esters claim 18 , co-polymerized methacrylic acid/acrylic acid ethyl esters claim 18 , or mixtures thereof.20. The method of claim 17 , wherein the resin particles are strong acidic cation exchange resins claim 17 , selected from the group consisting of polistirex claim 17 , polacrilex claim 17 , cholestyramine claim 17 , polacrilin or mixtures thereof.21. The method of claim 17 , wherein 40%-50% of said ADHD effective agent is present in said first plurality of drug-resin particles and 50-60% of said ADHD effective agent is present in said second plurality of drug-resin particles.22. The method of claim 21 , wherein about 45% of said ADHD effective agent is present in said first plurality of drug-resin particles and about 55% of said ADHD effective agent is present in said second plurality of drug-resin particles.23. The method of claim 17 , wherein said pharmaceutical composition is a liquid suspension claim 17 , chewable composition claim 17 , or an orally disintegrating tablet composition.24. The method of claim 17 , wherein said drug-resin particles comprise 25% l-amphetamine and 75% d-amphetamine.25. The method of claim 17 , wherein the amount of drug delivered to said subject by said pharmaceutical composition is about 5 mg/24 hours to about 30 mg/24 hours.26. The method of claim 17 , wherein the amount of said ADHD effective agent delivered is 0.25 mg/kg subject/day to 1.5 mg/kg subject/day.27. The method of claim 17 , wherein said pharmaceutical composition is characterized by a dissolution profile in an in vitro dissolution assay wherein 40-45% of the ADHD effective agent is released within the first 45 minutes after the drug-resin particles are introduced into an in vitro dissolution assay claim 17 , followed by a period of substantially no ADHD effective agent release from 45 minutes to 2 hours claim 17 , and concluding with period of from 2 to 8 hours during which substantially all of the remaining ADHD effective agent is released claim 17 , wherein the conditions of the dissolution assay are an initial dissolution medium of 0.1 N HCl claim 17 , and after 2 hours claim 17 , the medium is adjusted to a pH of about 6.8; and the dissolution assay is performed using a USP Apparatus 2.28. The method of claim 17 , wherein the delayed release coating releases substantially all of the ADHD effective agent in the second plurality of drug-resin particles within about 60 minutes after initiation of the delayed release.29. The method of claim 17 , wherein said pharmaceutical composition is sufficient to maintain a therapeutically effective level of said ADHD effective agent in the subject over the course of at least 8 hours without further administration of ADHD effective agent.30. The method of claim 17 , wherein the amount of ADHD effective agent is equivalent to the amount of ADHD effective agent present in 5 mg claim 17 , 10 mg claim 17 , 15 mg claim 17 , 20 mg claim 17 , 25 mg claim 17 , or 30 mg of a reference composition without resin particles which comprises a mixture of dextroamphetamine sulfate claim 17 , dextroamphetamine saccharate claim 17 , amphetamine aspartate claim 17 , and amphetamine sulfate.31. The method of claim 17 , wherein one or more in vivo pharmacokinetic parameters of said pharmaceutical composition selected from the group consisting of C claim 17 , AUC claim 17 , AUC claim 17 , AUC claim 17 , AUC claim 17 , AUC claim 17 , AUC claim 17 , AUC claim 17 , and AUC have a 90% confidence interval with upper and lower bounds within a range from 90%415% of the value of the same parameter(s) for a bioequivalent reference composition.32. The method of claim 17 , wherein 20%-50% of said ADHD effective agent is present in said first plurality of drug-resin particles and 50-80% of said ADHD effective agent is present in said second plurality of drug-resin particles.33. The method according to wherein said ADHD effective agent is a mixture of dextro- and levo-amphetamines.34. The method according to wherein said first plurality of drug-resin particles is uncoated.35. The method according to wherein said ADHD effective agent is a mixture of dextro- and levo-amphetamines.36. The method according to wherein said first plurality of drug-resin particles is uncoated.37. The method of wherein the composition is administered to the subject substantially contemporaneously with ethanol.