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 .- 11 . (canceled)
12 . A method of treating dyskinesia, comprising:
orally administering, once-daily to a human subject with Parkinson's disease who is taking levodopa, a pharmaceutical composition comprising 50 mg to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof in an extended release dosage form,
said extended release dosage form comprising a capsule containing coated pellets; wherein said coated pellets comprise 1) drug-containing pellets having an inert core covered with amantadine or a pharmaceutically acceptable salt thereof and a binder, and 2) a release-modifying coating layer on said drug-containing pellets,
said release-modifying coating layer comprises (i) a water insoluble polymer, (ii) 15% to 85% by weight of a water soluble pore forming material, and (iii) 0% to 50% by weight of a plasticizer, and
said pharmaceutical composition having an in vitro dissolution profile ranging between 0% and 20% in 1 hour, 70% or greater in 10 hours, and 90% or greater in 12 hours, using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±0.5° C. in water.
13 . The method of claim 12 , wherein said pharmaceutical composition has an in vitro dissolution profile in water of less than 10% in 30 minutes and more than 95% in 16 hours as determined using a USP type II (paddle) dissolution system at 50 rpm at a temperature of 37±0.5° C.
14 . The method of claim 12 , wherein 200 mg to 500 mg of amantadine or a pharmaceutically acceptable salt is administered daily to said human subject.
15 . The method of claim 12 , wherein said method reduces the frequency or severity of dyskinesia.
16 . The method of claim 12 , wherein said extended release dosage form provides a shift in amantadine Tmax of 2 hours to 16 hours relative to the Tmax of an immediate release form of amantadine when the Tmax of said extended release dosage form and the immediate release form are determined in a single dose human pharmacokinetic study.
17 . The method of claim 12 , wherein said extended release dosage form provides a shift in amantadine Tmax of 4 hours to 16 hours relative to the Tmax of an immediate release form of amantadine when the Tmax of said extended release dosage form and the immediate release form are determined in a single dose human pharmacokinetic study.
18 . The method of claim 12 , wherein said extended release dosage form provides a Tmax of 5 to 19 hours.
19 . The method of claim 12 , wherein said extended release dosage form provides a Tmax of 7 to 19 hours.
20 . The method of claim 12 , wherein said inert core is a sugar sphere, NF.
21 . The method of claim 12 , wherein said binder comprises hydroxypropyl methylcellulose.
22 . The method of claim 12 , wherein said water insoluble polymer comprises ethyl cellulose.
23 . The method of claim 12 , wherein said water soluble pore forming material comprises hydroxypropyl methyl cellulose.
24 . The method of claim 12 , wherein said water soluble pore forming material comprises polyvinylpyrrolidone.
25 . The method of claim 12 , wherein said composition is administered once daily in multiple dosage forms.
26 . The method of claim 12 , wherein said composition is encapsulated.