Composition and method for treating neurological disease
The present disclosure is directed to methods of treating neurological disorders in a patient such as Parkinson's disease, drug-induced extrapyramidal reactions, and/or levodopa-induced dyskinesia comprising administering to the patient once daily in the morning a pharmaceutical composition comprising about 50 mg to about 400 mg of extended-release amantadine or a pharmaceutically acceptable salt thereof.
1. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising:
i) amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and
ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form,
wherein the composition comprises about 129 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 35% in about 30 minutes, about 35% in about 1 hour, about 40% in about 1.5 hours, and no more than about 45% in about 2 hours, as measured in 5% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., wherein the in vitro dissolution profile is such that the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
2. The method of claim 1 , wherein the composition comprises 129 mg of amantadine free base.
3. The method of claim 1 , wherein the pharmaceutical composition has an in vitro dissolution profile of about 35% in about 30 minutes, about 40% in about 1 hour, about 45% in about 1.5 hours, and no more than about 55% in about 2 hours as measured in 20% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
4. The method of claim 3 , wherein the composition comprises 129 mg of amantadine free base.
5. The method of claim 3 , wherein the pharmaceutical composition has an in vitro dissolution profile of about 35% in about 30 minutes, about 45% in about 1 hour, about 55% in about 1.5 hours, and no more than about 65% in about 2 hours as measured in 40% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
6. The method of claim 5 , wherein the pharmaceutical composition comprises 129 mg of amantadine free base.
7. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising 1) amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises about 193 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 25% in about 30 minutes, about 25% in about 1 hour, about 30% in about 1.5 hours, and no more than about 35% in about 2 hours as measured in 5% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., wherein the in vitro dissolution profile is such that the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
8. The method of claim 7 , wherein the pharmaceutical composition comprises 193 mg of amantadine free base.
9. The method of claim 7 , wherein the pharmaceutical composition has an in vitro dissolution profile of about 20% in about 30 minutes, about 25% in about 1 hour, about 35% in about 1.5 hours, and no more than about 45% in about 2 hours as measured in 20% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
10. The method of claim 9 , wherein the pharmaceutical composition comprises 193 mg of amantadine free base.
11. The method of claim 9 , wherein the pharmaceutical composition has an in vitro dissolution profile of about 20% in about 30 minutes, about 35% in about 1 hour, about 45% in about 1.5 hours, and no more than about 55% in about 2 hours as measured in 40% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
12. The method of claim 11 , wherein the pharmaceutical composition comprises 193 mg of amantadine free base.
13. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising 1) amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises about 258 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 20% in about 30 minutes, about 25% in about 1 hour, about 30% in about 1.5 hours, and no more than about 45% in about 2 hours as measured in 5% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., wherein the in vitro dissolution profile is such that the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
14. The method of claim 13 , wherein the pharmaceutical composition comprises 258 mg of amantadine free base.
15. The method of claim 13 , wherein the pharmaceutical has an in vitro dissolution profile of about 20% in about 30 minutes, about 25% in about 1 hour, about 40% in about 1.5 hours, and no more than about 50% in about 2 hours as measured in 20% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
16. The method of claim 15 , wherein the pharmaceutical composition comprises 258 mg of amantadine free base.
17. The method of claim 15 , wherein the pharmaceutical has an in vitro dissolution profile of about 20% in about 30 minutes, about 30% in about 1 hour, about 45% in about 1.5 hours, and no more than about 55% in about 2 hours as measured in 40% (v/v) ethanol in 0.1N HCl using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C.
18. The method of claim 17 , wherein the pharmaceutical composition comprises 258 mg of amantadine free base.