Details 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 (Colleyville, TX), McMahen; Russell (Flower Mound, TX)
Assignee:	NEOS THERAPEUTICS, LP (Grand Prairie, TX)
Filing Date:	Mar 15, 2013
Application Number:	13/844,555
Claims:	1. A method for treating Attention-Deficit Disorder or Attention-Deficit Hyperactivity Disorder in a subject that has been substantially contemporaneously exposed to ethanol comprising administering, to such a subject that is in need of such treatment, a pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles, wherein said ADHD effective agent is amphetamine and said composition comprises a first plurality of drug-resin particles that provide for immediate release of said ADHD effective agent and a second plurality of drug-resin particles that are coated with a delayed release coating, and wherein the amount of ADHD effective agent released from said composition in up to 20% ethanol is substantially similar to the amount of ADHD effective agent released from said composition in the absence of ethanol. 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, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, carboxymethylethylcellulose, co-polymerized methacrylic acid/methacrylic acid methyl esters, co-polymerized methacrylic acid/acrylic acid ethyl esters, or mixtures thereof. 4. The method of claim 1, wherein the resin particles are strong acidic cation exchange resins, selected from the group consisting of polistirex, polacrilex, cholestyramine, 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, chewable composition, 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, followed by a period of substantially no ADHD effective agent release from 45 minutes to 2 hours, and concluding with period of from 2 to 8 hours during which substantially all of the remaining ADHD effective agent is released, wherein the conditions of the dissolution assay are an initial dissolution medium of 0.1 N HCl, and after 2 hours, 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, 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg of a reference composition without resin particles which comprises a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate, 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.sub.max, AUC.sub.0-5, AUC.sub.5-12, AUC.sub.5-24, AUC.sub.5-t, AUC.sub.0-12, AUC.sub.0-24, AUC.sub.0-t, and AUC.sub.0-.infin. 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, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, carboxymethylethylcellulose, co-polymerized methacrylic acid/methacrylic acid methyl esters, co-polymerized methacrylic acid/acrylic acid ethyl esters, or mixtures thereof. 20. The method of claim 17, wherein the resin particles are strong acidic cation exchange resins, selected from the group consisting of polistirex, polacrilex, cholestyramine, 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, chewable composition, 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, followed by a period of substantially no ADHD effective agent release from 45 minutes to 2 hours, and concluding with period of from 2 to 8 hours during which substantially all of the remaining ADHD effective agent is released, wherein the conditions of the dissolution assay are an initial dissolution medium of 0.1 N HCl, and after 2 hours, 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, 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg of a reference composition without resin particles which comprises a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate, 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.sub.max, AUC.sub.0-5, AUC.sub.5-12, AUC.sub.5-24, AUC.sub.5-t, AUC.sub.0-12, AUC.sub.0-24, AUC.sub.0-t, and AUC.sub.0-.infin. 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 claim 1 wherein said ADHD effective agent is a mixture of dextro- and levo-amphetamines. 34. The method according to claim 1 wherein said first plurality of drug-resin particles is uncoated. 35. The method according to claim 17 wherein said ADHD effective agent is a mixture of dextro- and levo-amphetamines. 36. The method according to claim 17 wherein said first plurality of drug-resin particles is uncoated. 37. The method of claim 1 wherein the composition is administered to the subject substantially contemporaneously with ethanol.