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 - 23 . (canceled) 
     
     
         24 . A sustained release oral composition comprising a therapeutically effective amount of 4-aminopyridine dispersed in a matrix that provides a release profile of 4-aminopyridine in the blood plasma of a patient extending over a period of at least six hours, wherein the matrix in which said 4-aminopyridine is dispersed comprises a hydrophobic polymer. 
     
     
         25 . The sustained release oral composition of  claim 24 , wherein the hydrophobic polymer is selected from the group consisting of a hydrophobic cellulose derivative, a fat, a wax, a hydrophobic polyacrylamide derivative, a hydrophobic methacrylic acid derivative, and mixtures thereof. 
     
     
         26 . The sustained release oral composition of  claim 25 , wherein the hydrophobic polymer is a cellulose derivative. 
     
     
         27 . The sustained release oral composition of  claim 26 , wherein the cellulose derivative is ethyl cellulose. 
     
     
         28 . The sustained release oral composition of  claim 25 , wherein the hydrophobic polymer is a fat. 
     
     
         29 . The sustained release oral composition of  claim 28 , wherein the fat is glycerol palmitostearate. 
     
     
         30 . The sustained release oral composition of  claim 25 , wherein the hydrophobic polymer is a wax. 
     
     
         31 . The sustained release oral composition of  claim 30 , wherein the wax is bees wax, glycowax, castor wax, carnauba wax, glycerol monostearate, or stearyl alcohol. 
     
     
         32 . The sustained release oral composition of  claim 25 , wherein the hydrophobic polymer is selected from the group consisting of ethyl cellulose, glycerol palmitostearate, bees wax, glycowax, castor wax, carnauba wax, glycerol monostearate, stearyl alcohol, and mixtures thereof. 
     
     
         33 . The sustained release oral composition of  claim 24  or  25 , wherein the hydrophobic polymer comprises from about 20 to about 96% w/w of the composition. 
     
     
         34 . The sustained release oral composition of  claim 24  or  25 , wherein the 4-aminopyridine is present in an amount of from about 0.1 to about 13% w/w of the composition. 
     
     
         35 . The sustained release oral composition of  claim 24  or  25 , wherein the matrix further comprises a hydrophilic polymer. 
     
     
         36 . The sustained release oral composition of  claim 24  further comprising one or more of the following excipients:
 a) a diluent selected from the group consisting of microcrystalline cellulose, lactose, sucrose, fructose, glucose, dextrose, a sugar, dibasic calcium phosphate, calcium phosphate, calcium sulfate, cellulose, ethylcellulose, a cellulose derivative, kaolin, mannitol, lactitol, maltitol, xylitol, sorbitol, a sugar alcohol, dry starch, saccharides, dextrin, maltodextrin, a polysaccharide, inositol, and mixtures thereof; 
 b) a glidant, wherein the glidant is colloidal silicon dioxide; 
 c) a disintegrant selected from the group consisting of starch, sodium starch glycollate, crospovidone, croscarmellose, microcrystalline cellulose, a low substituted hydroxypropyl cellulose, pectin, potassium methacrylate-divinylbenzene copolymer, poly(vinyl alcohol), thylamide, sodium bicarbonate, sodium carbonate, a starch derivative, dextrin, beta cyclodextrin, a dextrin derivative, magnesium oxide, clay, bentonite, and mixtures thereof; and 
 d) a lubricant selected from the group consisting of silicon dioxide, talc, stearic acid, magnesium stearate, calcium stearate, hydrogenated vegetable oil, sodium benzoate, sodium chloride, leucine carbowax, magnesium lauryl sulfate, and glyceryl monostearate, and mixtures thereof. 
 
     
     
         37 . The sustained release oral composition of  claim 24  or  25 , wherein the release profile of 4-aminopyridine in the blood plasma of a patient extends over a period of at least about twelve hours. 
     
     
         38 . The sustained release oral composition of  claim 24  or  25 , wherein the release profile of 4-aminopyridine in the blood plasma of a patient extends over a period of at least about twenty four hours.