COMPOSITIONS FOR THE TREATMENT OF CNS-RELATED CONDITIONS
The invention provides methods for treating CNS-related conditions with amantadine and donepezil, in which the amantadine is in an extended release form, wherein the extended release amantadine formulation provides a change in plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT of the same quantity of an immediate release form of amantadine.
1 - 20 . (canceled)
21 . A solid pharmaceutical composition, comprising:
a) 22.5 mg to 32.5 mg of a first drug, wherein the first drug is memantine or a pharmaceutically acceptable salt thereof;
b) 1 mg to 10 mg of a second drug, wherein the second drug is donepezil or a pharmaceutically acceptable salt thereof; and
c) at least one excipient;
wherein:
at least one of said at least one excipient modifies the release of the first drug to provide an extended release form of said first drug; and
the solid pharmaceutical composition is in a unit dosage form for once daily, oral administration to a human,
wherein said unit dosage form has in vitro dissolution for the first drug of less than 70% in one hour, less than 90% in two hours, greater than 40% in six hours, and greater than 85% in 12 hours,
wherein dissolution of said unit dosage form is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in water.
22 . The solid pharmaceutical composition of claim 21 , comprising 27.5 mg to 32.5 mg of the first drug.
23 . The solid pharmaceutical composition of claim 21 , comprising 5 mg to 10 mg of the second drug.
24 . The solid pharmaceutical composition of claim 21 , wherein said first drug is memantine, and said unit dosage form has a Tmax of at least 11 hours for memantine as determined from a human pharmacokinetic study.
25 . A solid pharmaceutical composition, comprising:
a) memantine or a pharmaceutically acceptable salt thereof, and
b) at least one excipient,
wherein:
the memantine or a pharmaceutically acceptable salt thereof is in an extended release form;
the solid pharmaceutical composition is in a unit dosage form for once daily, oral administration to a human; and
the solid pharmaceutical composition has a C max /C mean of approximately 2 or less for approximately 2 hours to at least 6 hours after oral administration to a human subject.
26 . The solid pharmaceutical composition of claim 25 , further comprising donepezil or a pharmaceutically acceptable salt thereof, and
wherein said unit dosage form has an in vitro dissolution for the memantine or a pharmaceutically acceptable salt thereof of less than 70% in one hour, less than 90% in two hours, greater than 40% in six hours, and greater than 85% in 12 hours,
wherein dissolution of said unit dosage form is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in water.
27 . A method of administering a pharmaceutical composition to a human patient, comprising administering to said human patient orally, once daily, a therapeutically effective dose of said pharmaceutical composition, wherein said pharmaceutical composition comprises:
a) 22.5 mg to 33.75 mg of a first drug, wherein the first drug is memantine or a pharmaceutically acceptable salt thereof;
b) 1 mg to 10 mg of a second drug, wherein the second drug is donepezil or a pharmaceutically acceptable salt thereof; and
c) at least one excipient;
wherein:
at least one of said at least one excipient modifies the release of the first drug to provide an extended release form of said first drug; and
the pharmaceutical composition is in a unit dosage form,
wherein said unit dosage form has in vitro dissolution for the first drug of less than 70% in one hour, less than 90% in two hours, greater than 40% in six hours, and greater than 85% in 12 hours,
wherein dissolution of said unit dosage form is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in water.
28 . The method of claim 27 , wherein the pharmaceutical composition comprises 27.5 mg to 32.5 mg of the first drug.
29 . The method of claim 27 , wherein the pharmaceutical composition comprises 5 mg to 10 mg of the second drug.
30 . The method of claim 27 , wherein said first drug is memantine, and said unit dosage form has a Tmax of at least 11 hours for memantine as determined from a human pharmacokinetic study.