DOSAGE FORMS FOR ORAL ADMINISTRATION AND METHODS OF TREATMENT USING THE SAME
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.
1 . A pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin to form drug-resin particles, wherein said composition comprises a first plurality of drug-resin particles that are not coated with a delayed release coating and a second plurality of drug-resin particles that are coated with a delayed release coating.
2 . The composition of claim 1 , wherein said first plurality of drug-resin particles are uncoated and/or the second plurality of drug-resin particles comprises a triggered release coating.
3 . The composition of claim 1 , wherein said ADHD effective agent is a mixture of dextro- and levo-amphetamines and/or methylphenidate.
4 - 6 . (canceled)
7 . The composition of claim 2 , wherein said triggered-release coating is pH dependent.
8 . (canceled)
9 . The composition of claim 2 , wherein said triggered-release coating is pH independent.
10 . The composition of claim 9 , wherein an enzyme secretion triggers said triggered-release coating.
11 . The composition of claim 9 , wherein the triggered-release coating is cross-linked gelatin, polylactic acid, cellophane, plastarch material, polycaprolactone, polyglycolide, poly-3-hydroxybutyrate, zein, materials susceptible to enzymatic activation by azo-reductases in intestinal bacteria, and materials susceptible to degradation in the colon.
12 - 16 . (canceled)
17 . The composition of claim 1 , wherein the resin particles are strong acidic cation exchange resins.
18 . The composition of claim 1 , wherein the resin particles are polistirex, polacrilex, cholestyramine, polacrilin or mixtures thereof.
19 - 25 . (canceled)
26 . The composition of claim 1 , wherein the composition is a liquid suspension, chewable composition, or an orally disintegrating tablet composition.
27 - 40 . (canceled)
41 . The composition of claim 1 , wherein the second plurality of drug-resin particles are coated with a water-soluble polymer overcoat.
42 - 43 . (canceled)
44 . The composition of claim 3 , wherein the composition consists essentially of amphetamine salts, wherein anions of said salts are polymeric.
45 . The composition of claim 1 , wherein the composition is or the drug-resin particles are substantially free of soluble anions.
46 - 47 . (canceled)
48 . A pharmaceutical composition for delivery of at least one ADHD effective agent, comprising: (a) at least one pharmaceutically active ADHD effective agent drug-resin complex providing for immediate release; and (b) at least one pharmaceutically active ADHD effective agent drug-resin complex covered with a delayed release coating, wherein said component (a) provides for an immediate release of ADHD effective agent from the drug resin complex to provide a first blood level of ADHD effective agent and component (b) provides a delayed release of ADHD effective agent from the drug-resin complex that increases the blood level of ADHD effective agent to a second level.
49 - 54 . (canceled)
55 . A method for treating Attention-Deficit Disorder or Attention-Deficit Hyperactivity Disorder comprising administering an effective amount of a pharmaceutical composition to a human patient, said composition comprising: an ADHD effective agent in an immediate release dosage form that provides immediate release upon oral administration to said patient; ADHD effective agent in a delayed release dosage form that provides delayed release upon oral administration to said patient; and a pharmaceutically acceptable carrier; wherein said ADHD effective agent is complexed with an ion-exchange resin to form a drug-resin complex
56 . The method of claim 55 , wherein the ADHD effective agent is at least one amphetamine and/or methylphenidate.
57 - 61 . (canceled)
62 . The method of claim 55 , wherein said pharmaceutical composition is sufficient to maintain an effective level of ADHD effective agent in the patient over the course of at least 8 hours without further administration of ADHD effective agent.
63 - 83 . (canceled)
84 . The method of claim 55 , wherein said subject suffers from dysphagia.
85 - 87 . (canceled)
88 . A method of treating fatigue or imparting alertness comprising administering an effective amount of the pharmaceutical composition of claim 1 to a subject in need thereof.
89 . A method of treating obesity comprising administering an effective amount of the pharmaceutical composition of claim 1 to a subject in need thereof.
90 . A method of making a pharmaceutical composition according to claim 1 comprising
(a) loading a plurality of resin particles with at least one ADHD effective agent to form loaded drug-resin particles;
(b) coating a portion of said loaded drug-resin particles with a delayed release coating to form coated drug-resin particles, said portion of loaded drug-resin particles optionally coated with an extended release coating; and
(c) combining said coated drug-resin particles with loaded, but uncoated drug-resin particles in a pharmaceutical composition.
91 . The method of claim 90 , wherein the at least one ADHD effective agent is at least one amphetamine and/or methylphenidate.
92 - 93 . (canceled)
94 . The method of claim 90 , wherein the delayed release coating is a triggered-release coating.
95 - 104 . (canceled)
105 . The method of claim 90 , wherein the extended release coating is a diffusion barrier coating.
106 - 112 . (canceled)
113 . The composition of claim 1 , wherein, for in vivo pharmacokinetic parameters of the composition, one or more in vivo pharmacokinetic parameters selected from the group consisting of C max , AUC 0-5 , AUC 5-12 , AUC 5-24 , AUC 5-t , AUC 0-12 , AUC 0-24 , AUC 0-t , and AUC 0-∞ have a 90% confidence interval with upper and lower bounds within a range from 90%-115% of the value of the same parameter(s) for a bioequivalent reference composition.
114 . The composition of claim 113 , wherein, for in vivo pharmacokinetic parameters of the composition, at least three in vivo pharmacokinetic parameters selected from the group consisting of C max , AUC 0-5 , AUC 5-12 , AUC 5-24, AUC 5-t , AUC 0-12 , AUC 0-24 , AUC 0-t , and AUC 0-∞ 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.
115 . The composition of claim 113 , wherein, for in vivo pharmacokinetic parameters of the composition, at least AUC 0-5 and AUC 5-t have a 90% confidence interval with upper and lower bounds within a range from 90%-115% of the value of the same parameter(s) for a bioequivalent reference composition.