Methods for treatment of attention deficit hyperactivity disorder

• US 9,034,902 B2
• Filed: 12/19/2014
• Issued: 05/19/2015
• Est. Priority Date: 03/23/2011
• Status: Active Grant

• Current Assignee: Ironshore Pharmaceuticals & Development, Inc.
• Original Assignee: Ironshore Pharmaceuticals & Development, Inc.
• Inventors: Lickrish, David, Zhang, Feng
• Primary Examiner(s): Gulledge, Brian
• Assistant Examiner(s): Cohen, Michael P
• Application Number:
  US14/577,963
• Publication Number:
  US 20150110868A1
• Time in Patent Office: 151 Days
• Field of Search: None
• US Class Current: 514/317
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine

Abstract

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate.

Claims

1. A method of treating a condition in a subject with a disorder or condition responsive to the administration of a methylphenidate, comprising orally administering an effective amount of methylphenidate or a pharmaceutical salt thereof in a formulation comprising a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient;

a sustained release layer enclosing the core and a delayed release layer enclosing the sustained release layer, wherein when the formulation provides an 8 hour lag time during which the formulation releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof;

followed by a sustained release period of 10-12 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl at pH 1.1, for up to 2 hours;

followed by 2-6 hours in sodium phosphate buffer at pH 6.0;

followed by 6-20 hours in sodium phosphate buffer, pH 7.2 at 37°

C.±

0.5°

C., measured by the USP Apparatus I.

2. The method of claim 1, wherein the formulation releases between about 0% and about 5% of the drug after 8 hours, between about 5% and about 30% after 10 hours, between about 20% and about 65% after 12 hours and between about 45% and about 95% after 15 hours, and wherein the rate of release between about 8 and 12 hours is lower than the rate of release from about 12 to about 16 hours.

3. The method of claim 1, wherein the formulation comprises a unit dose of methylphenidate or a pharmaceutical salt thereof, in a solid dosage form that comprises a sustained release formulation comprising the methylphenidate or a pharmaceutical salt thereof, enclosed in an outer coating that is insoluble in an aqueous medium at pH below 5.5, wherein when administered to a subject, the unit dose provides a lag period of at least 5 hours during which the subject'"'"'s plasma concentration of methylphenidate is less than 10% of the maximum concentration (C_max), wherein the plasma area under the curve at 10 hours (AUC_0-10) after administration to a human subject is less than about 7% of AUC_0-48, and wherein the time to C_max (T_max) is between 12 and 19 hours after administration.

4. The method of claim 3, wherein the plasma area under the curve at 6 hours (AUC_0-6) after administration is less than about 5% of the AUC_0-48.

5. The method of claim 3, wherein the plasma area under the curve at 6 hours (AUC_0-6) after administration is less than about 3% of the AUC_0-48.

6. The method of claim 1, wherein the outer coating comprises methacrylic acid copolymer type-B, mono- and di-glycerides and polysorbate 80.

7. The method of claim 1, wherein the sustained release formulation comprises a drug-containing core enclosed in a coating comprising ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:

3 to 1;

5, dibutyl sebacate and from 25% to 50% magnesium stearate.

8. The method of claim 1, wherein the disorder or condition is attention deficit disorder, attention deficit hyperactivity disorder, excessive daytime sleepiness, major depressive disorder, bipolar depression, negative symptoms in schizophrenia, chronic fatigue, fatigue associated with chemotherapy or binge eating disorder.

9. The method of claim 1, wherein the disorder or condition is attention deficit disorder or attention deficit hyperactivity disorder.

10. The method of claim 1, wherein the disorder is binge eating disorder.

11. The method of claim 1, wherein administration of the formulation is timed to allow the subject to sleep during the lag period and to have absorbed a therapeutic plasma level of drug upon awakening.

12. The method of claim 1, wherein the methylphenidate or pharmaceutical salt thereof is administered in a solid pharmaceutical composition comprising:

a water soluble capsule containing a plurality of beads, the beads comprising;

a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient;

a sustained release layer enclosing the core; and

a delayed release layer enclosing the sustained release layer.

13. The method of claim 1, wherein the formulation is administered to a patient in a fasted state.

14. The method of claim 1, wherein the formulation is administered at night.

15. A method of treating a condition in a subject with a disorder or condition responsive to the administration of a methylphenidate, comprising orally administering an effective amount of methylphenidate or a pharmaceutical salt thereof in a formulation comprising a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient;

a sustained release layer enclosing the core and a delayed release layer enclosing the sustained release layer, wherein when the formulation provides an 8 hour lag time during which the formulation releases no more than 1% of the total methylphenidate or a pharmaceutical salt thereof;

followed by a sustained release period of at least 8 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl at pH 1.1 for 2 hours, followed by hours 2-6 in sodium phosphate buffer at pH 6.0;

followed by hours 6-20 in sodium phosphate buffer at pH 7.2 and 37°

C.±

0.5°

C., as measured by the USP Apparatus I.

16. The method of claim 15, wherein the formulation releases no more than about 12% of the drug after 10 hours, no more than about 40% released after 12 hours and wherein the rate of release between about 8 and 10 hours is lower than the rate of release from about 10 to about 14 hours.

17. The method of claim 15, wherein the formulation releases no more than about 12% of the drug after 12 hours, no more than about 40% released after 14 hours and wherein the rate of release between about 10 and 12 hours is lower than the rate of release from about 12 to about 16 hours.