Composition and method for treating neurological disease
View Patent ↗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. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:
a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,
b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,
c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and
d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between 0 and 4 hours after administration.
2. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:
a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,
b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,
c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and
d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.
3. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:
a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,
b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,
c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and
d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT of the osmotic device is measured in a single dose human pharmacokinetic study over the time period between 2 hours and 4 hours after administration and the dC/dT provided by the same quantity of the drug in an immediate release form is measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.
4. The osmotic device of any of claims 1 to 3 , wherein the osmotic device comprises a total of 100 mg to 500 mg of the drug.
5. The osmotic device of any of claims 1 to 3 , wherein the osmotic device comprises a total of 200 mg to 500 mg of the drug.
6. The osmotic device of any of claims 1 to 3 , wherein at least 75% of the drug is provided in the core.
7. The osmotic device of any of claims 1 to 3 , wherein at least 90% of the drug is provided in the core.
8. The osmotic device of any of claims 1 to 3 , wherein the osmotic device provides a dC/dT that is less than 50% of the dC/dT provided by the same quantity of the drug in an immediate release form.
9. The osmotic device of any of claims 1 to 3 , wherein the osmotic device provides a dC/dT that is less than 40% of the dC/dT provided by the same quantity of the drug in an immediate release form.
10. The osmotic device of any of claims 1 to 3 , wherein the extent of drug bioavailability is maintained.
11. The osmotic device of any of claims 1 to 3 , wherein the osmotic device 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.