Claims for Patent: 9,498,447

Summary for Patent: 9,498,447

Title:	Compositions for treatment of attention deficit hyperactivity disorder
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.
Inventor(s):	Lickrish; David (Camana Bay, KY), Zhang; Feng (Pflugerville, TX)
Assignee:	Ironshore Pharmaceuticals & Development, Inc. (Camana Bay, KY)
Application Number:	15/069,734
Patent Claims:	1. A solid, oral pharmaceutical composition comprising: a single population of beads, said beads comprising: a core comprising methylphenidate or a pharmaceutical salt thereof; 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 a delayed release layer enclosing the sustained release layer, wherein the delayed release layer comprises a pH dependent polymer or copolymer that is insoluble in aqueous medium at pH lower than 5.5; wherein 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 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.degree. C..+-.0.5.degree. C., as measured by the USP Apparatus I. 2. The composition of claim 1, wherein the hydrophobic plasticizer is dibutyl sebacate. 3. The composition of claim 1, wherein the hydrophobic binder is a metal stearate. 4. The composition of claim 3, wherein the metal stearate is magnesium stearate. 5. The composition of claim 1, wherein the core comprises a substantially spherical bead. 6. The composition of claim 1, wherein the core comprises methylphenidate hydrochloride. 7. The composition of claim 1, wherein the core comprises microcrystalline cellulose. 8. The composition of claim 1, wherein the core comprises an inert, microcrystalline cellulose bead coated with a layer comprising methylphenidate or a pharmaceutical salt thereof. 9. The composition of claim 1, wherein the sustained release layer comprises ethyl cellulose, hydroxypropyl cellulose, dibutyl sebacate and a metal stearate. 10. The composition of claim 1, wherein the sustained release layer comprises ethyl cellulose, hydroxypropyl cellulose, dibutyl sebacate and magnesium stearate. 11. The composition of claim 1, wherein the delayed release layer comprises methacrylic acid copolymer Type B. 12. The composition of claim 1, wherein the delayed release layer comprises methacrylic acid copolymer Type B, mono- and diglycerides, dibutyl sebacate and polysorbate 80. 13. The composition of claim 1, wherein said population of beads is contained in a water soluble capsule. 14. The composition of claim 13, wherein the water soluble capsule contains from 1 mg to 150 mg of methylphenidate or a pharmaceutical salt thereof. 15. The composition of claim 14, wherein the water soluble capsule contains 80 mg of methylphenidate or a pharmaceutical salt thereof. 16. The composition 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% by weight magnesium stearate. 17. The composition of claim 1, wherein the delayed release layer comprises methacrylic acid copolymer type B, mono-and di-glycerides and polysorbate 80. 18. The composition of claim 1, wherein the formulation provides an 8 hour lag time during which the formulation releases no more than 5% of the total methylphenidate or a pharmaceutical salt thereof. 19. The composition of claim 1, wherein the formulation provides an 8 hour lag time during which the formulation releases no more than 3% of the total methylphenidate or a pharmaceutical salt thereof. 20. The composition of claim 1, wherein the release profile of percent released versus time in hours, is sigmoidal during the sustained release period. 21. The composition of claim 1, wherein the sustained release layer is coated to a weight gain of from 20 to 35%. 22. The composition of claim 1, wherein the delayed release layer is coated to achieve a weight gain of from 20 to 30%.