Compositions for treatment of attention deficit hyperactivity disorder
View Patent ↗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.
1. A solid, oral pharmaceutical 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 composition of claim 1 , wherein the core comprises methylphenidate hydrochloride.
3. The composition 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 composition of claim 1 , wherein the pH dependent copolymer is methacrylic acid copolymer Type B.
6. The composition of claim 1 , further comprising mono- and diglycerides, dibutyl sebacate and polysorbate 80.
7. The composition of claim 1 , contained in a single dosage form containing 1 mg to 150 mg of methylphenidate or a pharmaceutical salt thereof.
8. The composition of claim 1 , contained in a single dosage form containing 1 mg to 80 mg of methylphenidate or a pharmaceutical salt thereof.
9. The composition 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.