Suspensions and diluents for metronidazole and baclofen

Abstract

Suspensions of metronidazole or baclofen and/or salts or ester derivative thereof, such as metronidazole benzoate, are disclosed. The suspension my include metronidazole or baclofen, and /or a salt or ester derivative thereof a hydrocolloid stabilizer, simethicone emulsion, a buffer, such as sodium citrate, (dihydrate), a preservative, a thickening agent, a sweetener, and water.

What is claimed is: 
     
         1 . A liquid oral pharmaceutical composition of baclofen or a salt thereof, comprising:
 a) 5 mg/ml of baclofen or a salt thereof;   b) a hydrocolloid stabilizer, a thickening agent, or both, wherein the hydrocolloid stabilizer or thickening agent is selected from a group consisting of hydroxyethyl cellulose, microcrystalline cellulose, carboxymethylcellulose sodium, propylene glycol, and xanthan gum;   c) simethicone emulsion;   d) a buffer, wherein the buffer is selected from a citrate buffer, a tartrate buffer, an acetate buffer, a carbonate buffer, a phosphate buffer, a metaphosphate buffer, a glycerophosphate buffer, a polyphosphate buffer, and a pyrophosphate buffer;   e) a preservative selected from benzyl alcohol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), citric acid, sodium benzoate, benzoic, sodium bisulfate, sodium metabisulfite, sodium sulfite, parabens, potassium sorbate, vanillin, or any pharmaceutically acceptable salts thereof;   f) a sweetener, wherein the sweetener is one or more of glucose, fructose, sucrose, xylitol, maltodextrin, polydextrose, glycerin, inulin, maltol, acesulfame, alitame, aspartame, neotame, cyclamate, saccharin, or pharmaceutically acceptable salts thereof; and   g) water, wherein the pH of the liquid oral pharmaceutical composition is no more than 6.5, and   wherein the liquid oral pharmaceutical composition retains less than +/−5% variation of baclofen concentration measured by a USP assay for at least 30 days when stored at room temperature.   
     
     
         2 . The liquid oral pharmaceutical composition of  claim 1 , comprising a hydrocolloid stabilizer selected from hydroxyethyl cellulose, microcrystalline cellulose and carboxymethylcellulose sodium. 
     
     
         3 . The liquid oral pharmaceutical composition of  claim 1 , comprising a thickening agent selected from propylene glycol and xanthan gum. 
     
     
         4 . The liquid oral pharmaceutical composition of  claim 3 , wherein the propylene glycol is present at 5% (w/v). 
     
     
         5 . The liquid oral pharmaceutical composition of  claim 1 , wherein the thickening agent is present at 0.005-0.2% (w/v). 
     
     
         6 . The liquid oral pharmaceutical composition of  claim 1 , wherein the hydrocolloid stabilizer is present at 0.5% (w/v). 
     
     
         7 . The liquid oral pharmaceutical composition of  claim 1 , wherein the simethicone is a 30% simethicone emulsion and is present at 0.15-0.25% (w/v). 
     
     
         8 . The liquid oral pharmaceutical composition of  claim 1 , wherein the buffer is a citrate salt, a carbonate salt or a phosphate salt. 
     
     
         9 . The liquid oral pharmaceutical composition of  claim 1 , wherein the buffer is present at 0.1-0.9% (w/v). 
     
     
         10 . The liquid oral pharmaceutical composition of  claim 1 , wherein the preservative is sodium benzoate. 
     
     
         11 . The liquid oral pharmaceutical composition of  claim 1 , wherein the preservative is parabens or a pharmaceutically acceptable salt thereof 
     
     
         12 . The liquid oral pharmaceutical composition of  claim 1 , wherein the preservative is present at 0.1-0.2% (w/v). 
     
     
         13 . The liquid oral pharmaceutical composition of  claim 1 , wherein the sweetener is one or more of ammonium glycyrrhizate, sucralose, and saccharin sodium. 
     
     
         14 . The liquid oral pharmaceutical composition of  claim 1 , wherein the sweetener is present at 0.05-0.2% (w/v) or 0.01-0.05% (w/v). 
     
     
         15 . The liquid oral pharmaceutical composition of  claim 1 , wherein the liquid oral pharmaceutical composition retains less than +/−5% variation of baclofen concentration measured by a USP assay for at least 30 days when stored at 38-42° C. 
     
     
         16 . The liquid oral pharmaceutical composition of  claim 1 , wherein the liquid oral pharmaceutical composition retains less than +/−5% variation of baclofen concentration measured by a USP assay for at least 30 days when stored at 15-30° C. 
     
     
         17 . The liquid oral pharmaceutical composition of  claim 1 , wherein the liquid oral pharmaceutical composition retains less than +/−2% variation of baclofen concentration measured by a USP assay for at least 30 days when stored at room temperature. 
     
     
         18 . The liquid oral pharmaceutical composition of  claim 1 , wherein the pH of the liquid oral pharmaceutical composition is between 3.0 and 6.0. 
     
     
         19 . The liquid oral pharmaceutical composition of  claim 1 , wherein the liquid oral pharmaceutical composition further comprises a coloring agent, a flavoring agent, or a combination thereof 
     
     
         20 . The liquid oral pharmaceutical composition of  claim 1 , wherein the baclofen or a salt thereof is baclofen.