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 method for treating spasticity in a subject comprising administering a liquid oral pharmaceutical composition to the subject, wherein the liquid oral pharmaceutical composition comprises:
 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 method of  claim 1 , wherein treating spasticity comprises alleviating one or more symptoms selected from spasms, pain, stiffness, tightness, and cramping. 
     
     
         3 . The method of  claim 2 , wherein the one or more symptoms are caused by multiple sclerosis. 
     
     
         4 . The method of  claim 1 , wherein the subject is a child. 
     
     
         5 . The method of  claim 1 , wherein the subject is an adult or elderly. 
     
     
         6 . The method of  claim 1 , wherein the subject has multiple sclerosis. 
     
     
         7 . The method of  claim 1 , comprising a hydrocolloid stabilizer selected from hydroxyethyl cellulose, microcrystalline cellulose and carboxymethylcellulose sodium. 
     
     
         8 . The method of  claim 1 , comprising a thickening agent selected from propylene glycol and xanthan gum. 
     
     
         9 . The method of  claim 8 , wherein the propylene glycol is present at 5% (w/v). 
     
     
         10 . The method of  claim 1 , wherein the thickening agent is present at 0.005-0.2% (w/v). 
     
     
         11 . The method of  claim 1 , wherein the simethicone is a 30% simethicone emulsion and is present at 0.15-0.25% (w/v). 
     
     
         12 . The method of  claim 1 , wherein the buffer is a citrate salt, a carbonate salt, or a phosphate salt. 
     
     
         13 . The method of  claim 1 , wherein the buffer is present at 0.1-0.9% (w/v). 
     
     
         14 . The method of  claim 1 , wherein the preservative is parabens or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 1 , wherein the preservative is present at 0.1-0.2% (w/v). 
     
     
         16 . The method of  claim 1 , wherein the sweetener is one or more of ammonium glycyrrhizate, sucralose, and saccharin sodium. 
     
     
         17 . The method of  claim 1 , wherein the sweetener is present at 0.05-0.2% (w/v) or 0.01-0.05% (w/v). 
     
     
         18 . The method 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. 
     
     
         19 . The method 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. 
     
     
         20 . The method 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. 
     
     
         21 . The method of  claim 1 , wherein the pH of the liquid oral pharmaceutical composition is between 3.0 and 6.0. 
     
     
         22 . The method of  claim 1 , wherein the liquid oral pharmaceutical composition further comprises a coloring agent, a flavoring agent, or a combination thereof. 
     
     
         23 . The method of  claim 1 , wherein the baclofen or a salt thereof is baclofen.