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 or a thickening agent;   c) simethicone emulsion;   d) a buffer;   e) a preservative;   f) a sweetener; 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 , wherein the hydrocolloid stabilizer or the thickening agent is selected from propylene glycol, xanthan gum, hydroxyethyl cellulose, microcrystalline cellulose and carboxymethylcellulose sodium. 
     
     
         8 . The method of  claim 1 , wherein the thickening agent is present at 0.005-0.2% (w/v). 
     
     
         9 . The method of  claim 7 , wherein the propylene glycol is present at 5% (w/v). 
     
     
         10 . The method of  claim 1 , wherein the simethicone is a 30% simethicone emulsion and is present at 0.15-0.25% (w/v). 
     
     
         11 . The method of  claim 1 , wherein the buffer is selected from citrate, tartrates, acetates, carbonates, phosphates, metaphosphates, glycerophosphates, polyphosphates, pyrophosphates, and any pharmaceutically acceptable combination of anions and cation salts thereof. 
     
     
         12 . The method of  claim 11 , wherein the buffer is carbonate salt or phosphate salt. 
     
     
         13 . The method of  claim 1 , wherein the buffer is a pharmacologically acceptable combination of: cations selected from sodium, potassium, magnesium, calcium, and aluminum; and anions selected from bicarbonate, hydroxide, gluconate, glycinate, and amino acid salts. 
     
     
         14 . The method of  claim 1 , wherein the buffer comprises a citrate. 
     
     
         15 . The method of  claim 1 , wherein the buffer is present at 0.1-0.9% (w/v). 
     
     
         16 . The method of  claim 1 , wherein the preservative is selected from benzyl alcohol, ascorbic acid, ascrobyl 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. 
     
     
         17 . The method of  claim 16 , wherein the preservative is parabens or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 1 , wherein the preservative is present at 0.1-0.2% (w/v). 
     
     
         19 . The method of  claim 1 , 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. 
     
     
         20 . The method of  claim 1 , wherein the sweetener is one or more of ammonium glycyrrhizate, sucralose, and saccharin sodium. 
     
     
         21 . The method of  claim 1 , wherein the sweetener is present at 0.05-0.2% (w/v) or 0.01-0.05% (w/v). 
     
     
         22 . 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. 
     
     
         23 . 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. 
     
     
         24 . 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. 
     
     
         25 . The method of  claim 1 , wherein the pH of the liquid oral pharmaceutical composition is between 3.0 and 6.0. 
     
     
         26 . The method of  claim 1 , wherein the liquid oral pharmaceutical composition further comprises a coloring agent, a flavoring agent, or a combination thereof. 
     
     
         27 . The method of  claim 1 , wherein the baclofen or a salt thereof is baclofen.