Stabilization Of Moisture-Sensitive Drugs
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.
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.