Controlled release formulations of levodopa and uses thereof

摘要

The current invention provides a controlled release oral solid formulation of levodopa comprising levodopa, a decarboxylase inhibitor, and a carboxylic acid. Also provided by this invention is multiparticulate, controlled release oral solid formulations of levodopa comprising: i) a controlled release component comprising a mixture of levodopa, a decarboxylase inhibitor and a rate controlling excipient; ii) a carboxylic acid component; and iii) an immediate release component comprising a mixture of levodopa and a decarboxylase inhibitor.

主权项

1. A method for treating Parkinson's disease comprising orally administering to a human patient in need of such treatment a multiparticulate formulation comprising about 10 mg to about 300 mg of carbidopa and about 25 mg to about 1200 mg of levodopa wherein the multiparticulate formulation comprises:
a. an immediate release component comprising a mixture of carbidopa and levodopa in a ratio of about 1 to about 4; and b. a controlled release component comprising at least one controlled release excipient that provides for the controlled release of carbidopa, levodopa and a carboxylic acid that is not carbidopa or levodopa,wherein the molar ratio of carboxylic acid to levodopa in the controlled release component is greater than 1:4 and less than 4:1 and following oral administration of the multiparticulate formulation the carbidopa, levodopa and carboxylic acid are released over a period of time of about 6 hours, andwherein following a single dose administration of the multiparticulate formulation the patient's levodopa plasma concentration profile comprises:
(i) a time of administration; (ii) a first concentration that occurs at a first time and within one hour of the time of administration; (iii) a second concentration that occurs at a second time after said first time; and (iv) a third concentration that occurs after said second concentration and at a third time that is at least four hours after said second concentration, and the second concentration is the maximum concentration of levodopa in the profile; the first concentration is greater than or equal to about fifty percent of the second concentration; said third concentration is about fifty percent to about sixty percent of the second concentration and the levodopa plasma concentration decreases after the third concentration, andwherein the administration of the multiparticulate formulation is effective in alleviating at least one symptom of Parkinson's disease.