Compositions for treatment of attention deficit hyperactivity disorder

• US 10,617,651 B2
• Filed: 12/20/2018
• Issued: 04/14/2020
• 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): Cohen, Michael P
• Application Number:
  US16/227,932
• Publication Number:
  US 20190125689A1
• Time in Patent Office: 481 Days
• Field of Search: None
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• 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 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• 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 9/5078 with drug-free core
• 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

Abstract

Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period.

Claims

1. A method of treating a subject with a disorder or condition responsive to the administration of a methylphenidate, comprising:

orally administering an effective amount of a methylphenidate or a pharmaceutical salt thereof in a composition comprising coated particles, said particles comprising;

(a) a core comprising methylphenidate or a pharmaceutical salt thereof;

(b) a sustained release layer enclosing the core, wherein the sustained release layer comprises a water-insoluble and water-permeable polymer, a water-soluble polymer, a hydrophobic plasticizer, and a hydrophobic binder; and

(c) a pH dependent polymer or copolymer that is insoluble in aqueous medium at pH lower than 5.5;

wherein the formulation provides at least 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 pH 1.1, for up to 2 hours followed by 4 hours in sodium phosphate buffer at pH 6.0;

followed by 14 hours in sodium phosphate buffer, pH 7.2 at 37°

C.±

0.5°

C., as measured by the USP Apparatus I.

2. The method of claim 1, wherein the core comprises methylphenidate hydrochloride.

3. The method of claim 1, wherein the sustained release layer comprises ethyl cellulose, hydroxypropyl cellulose, dibutyl sebacate and a metal stearate.

4. The composition of claim 1, wherein the sustained release layer comprises ethyl cellulose, hydroxypropyl cellulose, dibutyl sebacate and magnesium stearate.

5. The method of claim 1, wherein the pH dependent copolymer is methacrylic acid copolymer Type B.

6. The method of claim 1, wherein the composition further comprise mono- and diglycerides, dibutyl sebacate and polysorbate 80.

7. The method of claim 1, wherein the composition is contained in a single dosage form containing 1 mg to 150 mg of methylphenidate or a pharmaceutical salt thereof.

8. The method of claim 1, wherein the composition is contained in a single dosage form containing 1 mg to 80 mg of methylphenidate or a pharmaceutical salt thereof.

9. The method of claim 1, wherein the sustained release layer comprises ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:

3 to 1;

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