Stabilization Of Moisture-Sensitive Drugs

Abstract

Described are stability-enhancing formulations of drugs that are sensitive to moisture. The formulations comprise co-granulates containing a moisture-sensitive drug and an excipient selected from fructose, xylitol, maltitol, and mixtures thereof. Also described are methods of producing a pharmaceutical tablet. The method comprises forming a blend of a moisture-sensitive drug and a first excipient selected from fructose, xylitol, maltitol, and mixtures thereof; spraying the blend with water to produce granules; drying and milling the granules; mixing a second excipient with the granules; and compressing into tablets.

What is claimed is: 
     
         1 . A pharmaceutical formulation comprising a co-granulate comprising a moisture-sensitive drug and an excipient comprising fructose. 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein the moisture-sensitive drug and fructose are present in a weight ratio of about 1:9. 
     
     
         3 . The pharmaceutical formulation of  claim 1 , wherein the moisture-sensitive drug comprises amlodipine, felodipine, fesoterodine, isradipine, nifedipine, nimodipine, or nisoldipine. 
     
     
         4 . The pharmaceutical formulation of  claim 1 , wherein the moisture-sensitive drug comprises fesoterodine fumarate. 
     
     
         5 . The pharmaceutical formulation of  claim 1 , further comprising a diluent, a binder, a drug stabilizer, a disintegrant, a glidant, a lubricant, a release rate modifier, a preservative, an antioxidant, a coating, a colorant, a flavoring agent, or combinations thereof. 
     
     
         6 . The pharmaceutical formulation of  claim 1 , wherein the moisture-sensitive drug comprises a drug compound that is susceptible to degradation by formation of one or more impurities. 
     
     
         7 . The pharmaceutical formulation of  claim 1 , wherein moisture-sensitive drug comprises a drug compound that is susceptible to degradation by deacylation and formation of an impurity comprising a deacylated drug compound. 
     
     
         8 . A method of producing a pharmaceutical tablet, the method comprising:
 forming a blend of a moisture-sensitive drug and a first excipient comprising fructose;   spraying the blend with water to produce granules;   drying and milling the granules;   mixing a second excipient with the granules; and   compressing into tablets.   
     
     
         9 . The method of  claim 8 , wherein a second excipient is selected from the group consisting of diluent, binder, drug stabilizer, disintegrant, glidant, lubricant, release rate modifier, preservative, antioxidant, coating, colorant, flavoring agent, or combinations thereof. 
     
     
         10 . The method of  claim 8 , wherein the moisture-sensitive drug comprises amlodipine, felodipine, fesoterodine, isradipine, nifedipine, nimodipine, or nisoldipine. 
     
     
         11 . The method of  claim 8 , wherein the moisture-sensitive drug comprises fesoterodine fumarate. 
     
     
         12 . The method of  claim 8 , wherein the granules are dried and milled to an average particle size of less than 1200 μm. 
     
     
         13 . The method of  claim 8 , further comprising coating the tablets with a coating suspension. 
     
     
         14 . A tablet for oral administration comprising a co-granulate consisting of fesoterodine fumarate and fructose in a ratio of about 1:9, and one or more additional pharmaceutically acceptable excipients.