Sustained release aminopyridine composition

Abstract

A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at least 12 hours, preferably 24 hours or more and the use of the composition to treat various neurological diseases.

1 . A process for preparing a sustained release 4-aminpyridine composition comprises the steps of:
 (a) milling 4-aminopyrdine to produce a particle size distribution such that 90% of the 4-aminopyridine particles are smaller than 300 μm, 50% of the 4-aminopyridine particles are smaller than 150 μm, and 10% of the 4-aminopyridine particles are smaller than 50 μm.   (b) dispersing the 4-aminpyridine from step (a) in a rate-controlling polymer by dry blending said 4-aminopyridine and said rate-controlling polymer for about from 10 to about 55 minutes, to form a blend and   (c) compressing the blend formed in step (b) to form one or more tablets.   
     
     
         2 . The process of  claim 1  further comprising adding a diluent, a glidant and/or a lubricant during the blending step (b). 
     
     
         3 . The process of  claim 2  wherein the blend is formed using 4-aminopyridine in an amount from about 0.5 to about 6.25% w/w; hydroxypropyl methylcellulose as the rate-controlling polymer in an amount from about 20 to about 96% w/w; and microcrystalline cellulose as the diluent in an amount from about 10 to about 80% w/w of the sustained release composition. 
     
     
         4 . The process of  claim 3  wherein each tablet comprises from about 5 mg to about 50 mg of 4-aminopyridine. 
     
     
         5 . The process of  claim 4  wherein each tablet comprises about 5 mg of 4-aminopyridine.