AMANTADINE COMPOSITIONS AND METHODS OF USE
Methods of nighttime administration of amantadine to reduce sleep disturbances in patient undergoing treatment with amantadine are described, as well as compositions of extended release amantadine that are suitable for nighttime administration.
1 .- 28 . (canceled)
29 . A pharmaceutical composition for once daily oral administration to a human subject, consisting of: (i) 50 mg to 445 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof; and (ii) one or more excipients, wherein at least one of said one or more excipients modifies the release of said drug to provide an extended release form,
wherein, said pharmaceutical composition has an in vitro dissolution profile characterized by release of said drug from said pharmaceutical composition that is not more than 25% in two hours and at least 80% at 12 hours using a USP Apparatus II (Paddles) at 50 rpm with 500 ml water at 37±0.5° C. as the dissolution medium, and
wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for amantadine is 8 to 18 hours.
30 . The pharmaceutical composition of claim 29 , wherein said Tmax for amantadine is 9 to 18 hours.
31 . The pharmaceutical composition of claim 29 , wherein said Tmax for amantadine is 11 to 18 hours.
32 . The pharmaceutical composition of claim 29 , wherein said dissolution profile is characterized by release of drug from said composition that is not more than 10% in one hour.
33 . The pharmaceutical composition of claim 29 , wherein said dissolution profile is characterized by release of drug from said composition that is 40% to 80% in 6 hours.
34 . The pharmaceutical composition of claim 32 , wherein said dissolution profile is characterized by release of drug from said composition that is 40% to 80% in 6 hours.
35 . The pharmaceutical composition of claim 29 , wherein said dissolution profile is characterized by release of drug from said composition that is 25% to 55% in 6 hours.
36 . The pharmaceutical composition of claim 32 , wherein said dissolution profile is characterized by release of drug from said composition that is 25% to 55% in 6 hours.
37 . The pharmaceutical composition of claim 29 , wherein said dissolution profile is characterized by release of drug from said composition that is 30% to 50% in 4 hours.
38 . The pharmaceutical composition of claim 32 , wherein said dissolution profile is characterized by release of drug from said composition that is 30% to 50% in 4 hours.
39 . The pharmaceutical composition of claim 33 , wherein said dissolution profile is characterized by release of drug from said composition that is 30% to 50% in 4 hours.
40 . The pharmaceutical composition of claim 29 , wherein said drug is 50 mg to 365 mg of said pharmaceutical composition.
41 . The pharmaceutical composition of claim 29 , wherein said drug is 50 mg to 215 mg of said pharmaceutical composition.
42 . The pharmaceutical composition of claim 29 , wherein said drug is 50 mg to 175 mg of said pharmaceutical composition.
43 . The pharmaceutical composition of claim 29 , wherein said drug is 50 mg to 95 mg of said pharmaceutical composition.
44 . The pharmaceutical composition of claim 29 , wherein said drug is 150 mg to 215 mg of said pharmaceutical composition.
45 . The pharmaceutical composition of claim 29 , wherein said drug is 150 mg to 195 mg of said pharmaceutical composition.
46 . The pharmaceutical composition of claim 29 , wherein said drug is 150 mg to 365 mg of said pharmaceutical composition.
47 . The pharmaceutical composition of claim 29 , wherein at least one of said one or more excipients in said pharmaceutical composition is beads, and said beads are coated.
48 . The pharmaceutical composition of claim 29 , wherein said pharmaceutical composition is encapsulated in one, two, or three capsules.
49 . The pharmaceutical composition of claim 47 , wherein said pharmaceutical composition is encapsulated in one, two, or three capsules.