COMPOSITION AND METHOD FOR TREATING NEUROLOGICAL DISEASE
Disclosed are compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and one or more excipients, wherein at least one of the excipients modifies release of amantadine. Methods of administering the same are also provided.
1 . A pharmaceutical composition suitable for once daily oral administration to a human subject consisting of
(i) 50 to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein at least 50% of the drug in the composition is in an extended release form, and wherein the composition has an in vitro dissolution profile ranging between 35% and 55% in 2 hours, 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±0.5° C. in water.
2 . A pharmaceutical composition suitable for once daily oral administration to a human subject consisting of
(i) 50 to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein at least 50% of the drug in the composition is in an extended release form and the extended release form of the composition has an in vitro dissolution profile ranging between 35% and 55% in 2 hours, 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±0.5° C. in water.
3 . A pharmaceutical composition suitable for once daily oral administration to a human subject consisting
(i) 50 to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein at least 50% of the drug in the composition is in an extended release form and the extended release form of the composition has an in vitro dissolution profile ranging between 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±0.5° C. in water.
4 . The composition of any one of claims 1 to 3 , wherein the extended release form comprises an osmotic device, which utilizes an osmotic driving force to provide extended release of amantadine.
5 . The composition of any one of claims 1 to 3 , wherein the amount of drug is 100 to 500 mg.
6 . The composition of any one of claims 1 to 3 , wherein the amount of drug is 200 to 500 mg.
7 . The composition of any one of claims 1 to 3 , wherein at least 75% of the drug in the composition is in an extended release form.
8 . The composition of any one of claims 1 to 3 , wherein at least 90% of the drug in the composition is in an extended release form.
9 . The composition of any one of claims 1 to 3 , wherein the composition provides a shift in amantadine Tmax of 2 hours to 16 hours relative to an immediate release form of amantadine, wherein the Tmax is measured in a single dose human pharmacokinetic study.
10 . The composition of any one of claims 1 to 3 , wherein the extent of drug bioavailability is maintained.
11 . The composition of any one of claims 1 to 3 , wherein at least some of the drug is in an immediate release form.