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:
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° C.±0.5° 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%.