Modified release formulation and methods of use

Abstract

A modified release pharmaceutical formulation includes about 30-70% N-(2-amino-4-(fluorobenzylamino)-phenyl)carbamic acid ethyl ester (retigabine), or a pharmaceutically acceptable salt, solvate or hydrate thereof, about 5-30% of a drug delivery matrix including hydroxypropylmethylcellulose (HPMC), about 1.0-10% of an anionic surfactant, and an enteric polymer. The pharmaceutical formulation produces a sustained plasma concentration of retigabine following administration to a subject for 4-20 hours longer than the time required for in vitro release of 80% of retigabine. A formulation includes about 30-70% N-(2-amino-4-(fluorobenzylamino)-phenyl)carbamic acid ethyl ester (retigabine), or a pharmaceutically acceptable salt, solvate or hydrate thereof, about 5-30% of a drug delivery matrix, and an agent for retarding release in the gastric environment. The plasma concentration vs. time profile of this formulation is substantially flat over an extended period lasting for about 4 hours to about 36 hours. A method of treating a disorder characterized by nervous system hyperexcitability includes administering to a subject an effective amount of these pharmaceutical formulations.

Description

Background of the invention

[0001] This application claims priority to US Provisional Application No. 61 / 082,162, filed July 18, 2008, which is hereby incorporated by reference in its entirety.

[0002] The present invention relates to a pharmaceutical composition, more particularly to a pharmaceutical preparation for effectively treating nervous system hyperexcitability.

[0003] Many solid oral pharmaceuticals such as tablets or capsules are formulated to release the active ingredient immediately after ingestion. Generally, this immediate release (IR) dosage form results in very high initial plasma levels followed by a rapid decline. A possible consequence of an immediate-release dosage form is that patients experience fluctuations in different blood levels, which may result in a brief therapeutic overload followed by a period of therapeutic underdosing. These fluctuations or peaks and valleys in blood levels are difficult to regulate, reducing the overall therapeutic effe...

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