Orally effective methylphenidate extended release powder and aqueous suspension product

摘要

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile.

主权项

1. A powder which when admixed with water forms an aqueous oral suspension, said powder comprising (i) an immediate release methylphenidate component, (ii) a sustained release water-insoluble, water-permeable, pH-independent, barrier coated methylphenidate-ion exchange resin complex, and (iii) a buffering agent which adjusts the pH of the oral aqueous suspension comprising the powder to a pH of about 4.2,
wherein the oral aqueous suspension provides a pharmacokinetic profile in which d-methylphenidate has an area under the curve (AUC)0-∞ of about 114 ng-hr/mL to about 180 ng-hr/mL and a Cmax of about 11 ng/mL to about 17 ng/mL following a single oral administration of the oral aqueous suspension to adult subjects under fasted conditions at a dose equivalent to 60 mg racemic methylphenidate HCl.