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 method comprising:
orally administering to a human subject with Parkinson's disease once-daily a composition consisting of
(i) 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, and
wherein the daily dose of drug administered to the human subject is 200 to 500 mg.
2. A method comprising:
orally administering to a human subject with Parkinson's disease once-daily a composition consisting of
(i) 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, and
wherein the daily dose of drug administered to the human subject is 200 to 500 mg.
3. A method comprising:
orally administering to a human subject with Parkinson's disease once-daily a composition consisting of
(i) 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, and
wherein the daily dose of drug administered to the human subject is 200 to 500 mg.
4. The method of any one of claims 1 to 3 , wherein the daily dose of drug administered is 300 to 500 mg.
5. The method of any one of claims 1 to 3 , wherein at least 75% of the drug in the composition is in an extended release form.
6. The method of any one of claims 1 to 3 , wherein at least 90% of the drug in the composition is in an extended release form.
7. The method of any one of claims 1 to 3 , wherein at least some of the drug is in an immediate release form.
8. The method of any one of claims 1 to 3 , wherein the dose administered is therapeutically effective for the treatment of Parkinson's disease.
9. The method of any one of claims 1 to 3 , wherein the human subject with Parkinson's disease suffers from dyskinesia.
10. The method of claim 9 , wherein the method reduces the frequency or severity of dyskinesia.
11. The method of claim 9 , wherein the dyskinesia is levodopa-induced dyskinesia.
12. The method of any one of claims 1 to 3 , additionally comprising administering to the subject a pharmaceutically effective amount of levodopa/carbidopa.
13. The method 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.
14. The method 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 the drug.
15. The method of any one of claims 1 to 3 , wherein the extent of drug bioavailability is maintained.
16. The method of any one of claims 1 to 3 , wherein the once-daily administration of the composition is at a therapeutically-effective dose from the onset of therapy.