Orally effective methylphenidate extended release powder and aqueous suspension product
DC CAFCFirst Claim
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.
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Abstract
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.
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Citations
22 Claims
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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.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. 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 comprising the powder further comprises at least about 80% of water based on the total weight of the suspension, wherein the oral aqueous suspension has less than about 1% of threo-α - -phenyl-2-piperidineacetic acid hydrochloride impurity after a period of about 1 month of storage at room temperature, and
wherein following a single oral administration of the aqueous oral suspension to adult subjects under fasted conditions, at a dose equivalent to 60 mg racemic methylphenidate HCl, the oral aqueous suspension has 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 in adults under fasted conditions,a Cmax of about 11 ng/mL to about 17 ng/mL in adults, and wherein following a single administration of the aqueous oral suspension to adult, the d-methylphenidate has a reduced Tmax in adults subjects fed with a high-fat meal prior to administration compared to adult subjects in a fasted state prior to administration. - View Dependent Claims (22)
- -phenyl-2-piperidineacetic acid hydrochloride impurity after a period of about 1 month of storage at room temperature, and
Specification