Extended-release topiramate capsules

Abstract

An extended-release topiramate capsule that includes a capsule shell containing a single population of coated particles; wherein each coated particle includes a core and a coating thereon; wherein each particle core includes a homogeneous mixture comprising topiramate throughout its core; and wherein the coating includes one or more release controlling agent(s).

1 - 30 . (canceled) 
     
     
         31 . An extended-release topiramate capsule comprising:
 a capsule shell comprising a single population of coated particles;
 wherein each coated particle comprises a core and a coating thereon; 
 wherein each particle core comprises a homogeneous mixture comprising topiramate throughout its core; and 
   wherein the coating comprises one or more release controlling agent(s).   
     
     
         32 . The capsule of  claim 31  wherein:
 each particle core comprises a homogeneous mixture comprising:
 topiramate; 
 one or more filler(s); and 
 one or more binder(s); and 
 
 the coating comprises:
 one or more release controlling agent(s); 
 one or more pore former(s); and 
 one or more plasticizer(s). 
 
 
     
     
         33 . The extended-release topiramate capsule of  claim 31  wherein the particles are coated in an amount sufficient to provide a weight gain of 10% to 12%. 
     
     
         34 . The extended-release topiramate capsule of  claim 31  wherein the one or more filler(s) is selected from the group of microcrystalline cellulose, dibasic calcium phosphate, lactose, tribasic calcium phosphate, mannitol, and combinations thereof. 
     
     
         35 . The extended-release topiramate capsule of  claim 31  wherein the one or more binder(s) is selected from the group of hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxyethylcellulose, polyvinyl pyrrolidine, starch, natural gum, and combinations thereof. 
     
     
         36 . The extended-release topiramate capsule of  claim 31  wherein the one or more release controlling agent(s) is selected from the group of ethylcellulose, polyvinyl acetate, polyacrylate and polymethacrylate, copolymers thereof, and combinations thereof. 
     
     
         37 . The extended-release topiramate capsule of  claim 31  wherein the one or more pore former(s) is selected from the group of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyethylene glycol, guar gum, xanthan gum, sodium alginate, polyvinylpyrrolidone, crospovidone, sodium starch glycolate, croscarmellose sodium, starch, mannitol, glucose, sucrose, fructose, mannose, galactose, sorbitol, dextran, sodium chloride, potassium chloride, calcium chloride, and combinations thereof. 
     
     
         38 . The extended-release topiramate capsule of  claim 31  wherein the one or more plasticizer(s) is selected from the group of diethyl phthalate, triethyl citrate, dibutyl sebacate, polyethylene glycol, triacetin, tributyl citrate, glycerol, propylene glycol, and combinations thereof. 
     
     
         39 . The extended-release topiramate capsule of  claim 31  wherein each particle core further comprises one or more stabilizer(s). 
     
     
         40 . The extended-release topiramate capsule of  claim 39  wherein the one or more stabilizer(s) is selected from the group of calcium hydroxide, calcium carbonate, sodium bicarbonate, magnesium carbonate, and combinations thereof. 
     
     
         41 . The extended-release topiramate capsule of  claim 31  which, when dosed to a healthy human subject once daily (e.g., in the morning or evening), achieves at steady-state, an AUC 0-24h , C max  and C min  in the subject's plasma that are within the 80% to 125% bioequivalence criteria compared to immediate-release topiramate dosed twice per day. 
     
     
         42 . The extended-release topiramate capsule of  claim 31  which, when dosed to a healthy human subject once daily in the morning, achieves at steady-state, a reduction of fluctuation index of at least 15% compared to immediate-release topiramate dosed twice per day. 
     
     
         43 . The extended-release topiramate capsule of  claim 31  which, when dosed to a healthy human subject once daily in the morning, achieves at steady-state, a C min  in the subject's plasma that is higher than the C min  compared to immediate-release topiramate dosed twice per day. 
     
     
         44 . The extended-release topiramate capsule of  claim 31  which, when given as a single-dose to a healthy human subject, achieves an AUC 0-inf  of 170 to 210 h·μg/mL within a 95% confidence interval, and a C min  of 2 to 4 μg/mL within a 95% confidence interval. 
     
     
         45 . The extended-release topiramate capsule of  claim 31  which, when dosed once daily to a population of human patients suffering from epilepsy, achieves a reduction in incidence of at least one side effect compared to immediate-release topiramate dosed at the same total daily dose divided twice per day. 
     
     
         46 . The extended-release topiramate capsule of  claim 31  which is chemically stable for at least 12 months. 
     
     
         47 . The extended-release topiramate capsule of  claim 46  which is chemically stable for at least 24 months when stored in a sealed container with desiccant. 
     
     
         48 . The extended-release topiramate capsule of  claim 31  which is free of an immediate release component. 
     
     
         49 . The extended-release topiramate capsule of  claim 31  wherein the coated particles have a sphericity of at least 0.7. 
     
     
         50 . The extended-release topiramate capsule of  claim 31  wherein the coated particles have a particle size of at least 500 μm. 
     
     
         51 . The extended-release topiramate capsule of  claim 31  wherein the coated particles have a particle size of up to 1300 μm. 
     
     
         52 . The extended-release topiramate capsule of  claim 31  wherein the capsule shell comprises hydroxypropyl methylcellulose or gelatin. 
     
     
         53 . A container comprising an extended-release topiramate capsule of  claim 31  and desiccant. 
     
     
         54 . The container of  claim 53  wherein the ratio of weight of desiccant to weight of filled capsules is at least 0.01. 
     
     
         55 . The container of  claim 53  wherein the ratio of weight of desiccant to weight of filled capsules is up to 0.9. 
     
     
         56 . The container of  claim 53  wherein the desiccant is selected from silica gel, bentonite clay, molecular sieve, and combinations thereof. 
     
     
         57 . A method of dosing a subject in need thereof, the method comprising administering an extended-release topiramate capsule of  claim 31  once daily to the subject. 
     
     
         58 . The method of  claim 57  wherein the administering occurs once daily in the morning. 
     
     
         59 . The method of  claim 57  wherein the administering occurs once daily in the evening. 
     
     
         60 . The method of  claim 57  wherein the dosing is for the treatment of convulsions. 
     
     
         61 . The method of  claim 57  wherein the dosing is for the prophylactic treatment of a migraine.