Pharmaceutical composition of topiramate

Abstract

The invention is directed to a pharmaceutical composition of topiramate, an anticonvulsant which is useful for treating epilepsy. More specifically, the present invention provides a solid dosage formulation of topiramate intended primarily for use by pediatric patients, or for patients who have difficulty swallowing tablets. Processes for preparing the pharmaceutical composition are also described.

1 . A process for forming a pharmaceutical composition comprising: 
 (a) preparing core particles comprising an active agent of topiramate, a binder and a diluent wherein the diluent is sugar spheres, and;    (b) drying the core particles from step (a) to form dried core particles;    (c) coating the dried core particles from step (b) with a taste masking mixture to form coated particles; and    (d) drying the coated particles from step (c) to form the pharmaceutical composition wherein the amount of taste masking mixture ranges from about 9% by weight to about 13% by weight of the pharmaceutical composition.    
   
   
       2 - 4 . (canceled)  
   
   
       5 . The process of  claim 1 , wherein the dried core particles of step (b) are sized to between about 0.710 mm and about 1.18 mm prior to coating with the taste masking mixture.  
   
   
       6 . The process of  claim 5 , wherein the coated particles from step (d) are sized to between about 0.850 mm and about 1.18 mm.  
   
   
       7 . The process of  claim 6 , wherein the core particles are prepared by spraying a suspension of topiramate and the binder in a solvent onto the sugar spheres.  
   
   
       8 . The process of  claim 7 , wherein the binder is selected from povidone, HPMC, acacia gum, sugar, molasses, sodium alginate, panwar gum, starch, pregelatinized starch, carboxymethylcellulose, ethylcellulose or methylcellulose.  
   
   
       9 . The process of  claim 8 , wherein the binder is povidone.  
   
   
       10 . The process of  claim 8 , wherein the taste masking mixture comprises a taste masking agent selected from cellulose acetate, cellulose acetate buytrate, methylcellulose, ethylcellulose or a Eudragit; and a disintegrant selected from povidone, methylcellulose, starch, sodium starch glycolate, pregelatinized starch, cellulose, carboxymethylcellulose, croscarmellose sodium, magnesium aluminate silicate, alginic acid or guar gum.  
   
   
       11 . The process of  claim 10 , wherein the taste masking mixture comprises cellulose acetate and povidone.  
   
   
       12 . The process of  claim 11 , further comprising encapsulating the dried coated particles from step (d).  
   
   
       13 . A pharmaceutical composition made by the process of  claim 1 .  
   
   
       14 . A pharmaceutical composition comprising 
 (a) core particles containing an active agent of topiramate, a binder and a diluent wherein the diluent is sugar spheres, and wherein the core particles have an initial particle size between about 0.710 and about 1.18 mm; and    (b) a taste mask coating, wherein the taste mask coating comprises between about 9% by weight and about 13% by weight of the pharmaceutical composition and wherein the coated particles of the pharmaceutical composition have a final particle size between about 0.850 and about 1.18 mm.    
   
   
       15 - 17 . (canceled)  
   
   
       18 . The pharmaceutical composition of  claim 14 , wherein the taste mask coating comprises about 11% by weight of the pharmaceutical composition.  
   
   
       19 - 20 . (canceled)  
   
   
       21 . The pharmaceutical composition of  claim 14 , wherein the binder is selected from povidone, HPMC, sodium alginate, panwar gum, acacia gum, gelatin, sugar, molasses, starch, pregelatinized starch, methycellulose, ethylcellulose or caroboxymethylcellulose; and the taste mask coating comprises a taste masking agent and a disintegrant, wherein the taste masking agent is selected from cellulose acetate, methylcellulose, ethylcellulose, a Eudragit or cellulose acetate butyrate; and the disintegrant is selected from povidone, cellulose, carboxymethylcellulose, croscarmellose sodium, magnesium aluminate silicate, starch, sodium starch glycolate, pregelatinized starch, alginic acid or guar gum.  
   
   
       22 . The pharmaceutical composition of  claim 21 , wherein the binder is povidone, the taste masking agent is cellulose acetate and the disintegrant is povidone.  
   
   
       23 . The pharmaceutical composition of  claim 22 , wherein the coated particles of the pharmaceutical composition are encapsulated.  
   
   
       24 . A pharmaceutical composition comprising about 85 to about 93% by weight core beads, and about 7 to about 15% by weight of a coating; wherein the core beads comprise about 18 to about 21% by weight of topiramate, about 8 to about 11% by weight of povidone, and about 58 to about 61% by weight of sugar spheres; and the coating comprises about 6 to about 9% by weight of cellulose acetate, and about 2 to about 5% by weight of povidone.  
   
   
       25 . The pharmaceutical composition of  claim 24 , comprising about 89% by weight of core beads and about 11% by weight coating, wherein the core beads comprise about 19.8% by weight topiramate, about 9.9% by weight povidone, and about 59.3% by weight sugar spheres; and the coating comprises about 7.2% by weight cellulose acetate and about 3.8% by weight povidone.  
   
   
       26 . A method of treating convulsions which comprises administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 22 .  
   
   
       27 . A method of treating epilepsy which comprises administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 14 .  
   
   
       28 . A method of treating epilepsy which comprises administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 22 .  
   
   
       29 . A method of treating epilepsy which comprises administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 24 .  
   
   
       30 . A method of treating convulsions which comprises administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 24.