Process for preparing non-hygroscopic sodium valproate composition

Abstract

The invention provides a process for preparing a non-hygroscopic, highly stable, oral pharmaceutical composition of a salt of valproic acid. The pharmaceutical composition is prepared by blending ingredients including a hygroscopic salt of valproic acid, carbomer, and a non-hygroscopic additive such as dibasic calcium phosphate. Such a composition forms non-hygroscopic, highly moisture stable solid dosage form.

What is claimed is:  
     
         1 . A process for preparing a non-hygroscopic highly stable oral pharmaceutical composition of a salt of valproic acid, said process comprising the single step of blending ingredients including a hygroscopic salt of valproic acid, carbomer, and a non-hygroscopic additive.  
     
     
         2 . The process of  claim 1 , wherein said hygroscopic salt of valproic acid is sodium valproate.  
     
     
         3 . The process of  claim 1 , further comprising the step of adding at list one excipient.  
     
     
         4 . The process of  claim 1 , further comprising the step of compressing said ingredients into a solid dosage form after said step of blending.  
     
     
         5 . The process of  claim 4 , wherein a single dose of said solid dosage form contains from about 50 to about 1200 mg of sodium valproate.  
     
     
         6 . The process of  claim 2 , wherein said sodium valproate is present in an amount of from about 5% to about 99% of the weight of the final composition.  
     
     
         7 . The process of  claim 4 , wherein a single dose of said solid dosage form contains from about 0.2 mg to about 500 mg of carbomer.  
     
     
         8 . The process of  claim 1 , wherein said carbomer is present in an amount of from about 0.2% to about 30% of the weight of the final composition.  
     
     
         9 . The process of  claim 1 , wherein said carbomer is present in an amount such that the weight ratio of carbomer to sodium valproate is in the range of from about 0.3:99.7 to about 35:65.  
     
     
         10 . The process of  claim 1 , wherein said non-hygroscopic additive is selected from the group consisting of dibasic calcium phosphate anhydrous, calcium silicate, microcrystalline cellulose and mixtures thereof.  
     
     
         11 . The process of  claim 10 , wherein said dibasic calcium phosphate anhydrous is present in an amount of from about 10% to about 40% of the weight of the final composition.  
     
     
         12 . The process of  claim 10 , wherein said dibasic calcium phosphate anhydrous is present in an amount such that the weight ratio of dibasic calcium phosphate anhydrous to carbomer is in the range of from about 99.95:0.05 to about 40:60.  
     
     
         13 . The process of  claim 3 , wherein said excipient is selected from the group consisting of lubricants, disintegrators, glidents, adsorbents, and mixtures thereof.  
     
     
         14 . The process of  claim 13 , wherein said lubricant is selected from the group consisting of stearic acid, a salt of stearic acid, talc, sodium lauryl sulfate, sodium stearyl fumarate and mixtures thereof.  
     
     
         15 . The process of  claim 13 , wherein said lubricant is present in an amount of from about 0.25% to about 5% of the weight of the final composition.  
     
     
         16 . The process of  claim 13 , wherein said disintegrator is selected from the group consisting of crosscarmelose sodium, sodium starch glycolate, starch, magnesium aluminum silicate, colloidal silicon dioxide, carboxymethyl cellulose, microcrystalline cellulose, and mixtures thereof.  
     
     
         17 . The process of  claim 13 , wherein said disintegrator is present in an amount of from about 0.5% to about 25% of the weight of the final composition.  
     
     
         18 . The process of  claim 13 , wherein said glident is selected from the group consisting of colloidal silicon dioxide, talc and mixtures thereof.  
     
     
         19 . The process of  claim 13 , wherein said glident is present in an amount of from about 0.1% to about 10% of the weight of the final composition.  
     
     
         20 . The process of  claim 13 , wherein said adsorbent is selected from the group consisting of colloidal silicon dioxide, microcrystalline cellulose, calcium silicate and mixtures thereof.  
     
     
         21 . The process of  claim 13 , wherein said adsorbent is present in an amount of from about 0.05% to about 42% of the weight of the final composition.  
     
     
         22 . The process of  claim 4 , wherein said solid dosage form is selected from the group consisting of a tablet, a caplet, a pellet, a capsule, a tablet which disintegrates into granules, and a pill.  
     
     
         23 . The process of  claim 1 , wherein said pharmaceutical composition exists in a form selected from the group consisting of a capsule, a sachet, a powder and a granule.  
     
     
         24 . The process of  claim 1 , comprising the additional step of maintaining relative humidity in the range of about 30% to about 75% during said step of blending of said ingredients.  
     
     
         25 . A non-hygroscopic highly stable orally deliverable pharmaceutical composition for release of a salt of valproic acid into the bloodstream at a physiologically effective level, said composition comprising a pharmaceutically effective amount of a hygroscopic salt of valproic acid, a carrier, a non-hygroscopic additive, and at least one excipient.  
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein said hygroscopic salt of valproic acid is sodium valproate.  
     
     
         27 . The pharmaceutical composition of  claim 25 , wherein said carrier is selected from the group consisting of a polymeric carrier, a non-polymeric carrier and mixtures thereof.  
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein said polymeric carrier is carbomer.  
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein said carbomer is present in an amount of from about 0.2% to about 30% of the weight of the final composition.  
     
     
         30 . The pharmaceutical composition of  claim 27 , wherein said non-polymeric carrier is selected from the group consisting of a sugar, a protein, a biologically inert material, elemental carbon and mixtures thereof.  
     
     
         31 . The pharmaceutical composition of  claim 25 , wherein said pharmaceutically effective amount is selected from the group consisting of: 
 (a) less than 10% by weight of the total formulation; and    (b) more than 80% by weight of the total formulation.    
     
     
         32 . A method of treating a medical condition in a human patient, the method comprising the step of orally administering a non-hygroscopic highly stable pharmaceutical composition for release of a salt of valproic acid into the bloodstream at a physiologically effective level; 
 wherein said composition comprises a pharmaceutically effective amount of a hygroscopic salt of valproic acid, a carrier, a non-hygroscopic additive, and at least one excipient.    
     
     
         33 . The method of  claim 32 , wherein said medical condition is selected from the group consisting of epilepsy, a psychotic disorder and a migraine headache.