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 . A method of dosing a subject for the prophylactic treatment of a migraine, the method comprising:
 administering an extended-release topiramate capsule once daily to the subject, wherein the extended-release topiramate capsule comprises:
 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); 
 
   wherein the extended-release topiramate capsule, 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 max  of 2 to 4 μg/mL within a 95% confidence interval.   
     
     
         32 . The method of  claim 31  wherein the extended-release topiramate capsule, when dosed to a healthy human subject once daily, 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. 
     
     
         33 . The method of  claim 31  wherein the extended-release topiramate capsule, 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. 
     
     
         34 . The method of  claim 31  wherein the extended-release topiramate capsule, 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. 
     
     
         35 . The method of  claim 31  wherein the administering occurs once daily in the morning. 
     
     
         36 . The method of  claim 31  wherein the administering occurs once daily in the evening. 
     
     
         37 . The method of  claim 31  wherein the extended-release topiramate capsule is free of an immediate release component. 
     
     
         38 . The method 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). 
 
 
     
     
         39 . The method of  claim 38  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. 
     
     
         40 . The method of  claim 38  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. 
     
     
         41 . The method of  claim 38  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. 
     
     
         42 . The method of  claim 38  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. 
     
     
         43 . The method of  claim 38  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. 
     
     
         44 . The method of  claim 38  wherein each particle core further comprises one or more stabilizer(s). 
     
     
         45 . The method of  claim 44  wherein the one or more stabilizer(s) is selected from the group of calcium hydroxide, calcium carbonate, sodium bicarbonate, magnesium carbonate, and combinations thereof. 
     
     
         46 . The method of  claim 38  wherein the extended-release topiramate capsule comprises 40 wt-% to 50 wt-% of topiramate, based on the total weight of an uncoated particle core. 
     
     
         47 . The method of  claim 38  wherein the extended-release topiramate capsule comprises 3 wt-% to 7 wt-% of one or more binder(s), based on the total weight of an uncoated particle core. 
     
     
         48 . The method of  claim 38  wherein the extended-release topiramate capsule comprises 55 wt-% to 65 wt-% of one or more release controlling agent(s), based on the total weight of the coating. 
     
     
         49 . The method of  claim 38  wherein the extended-release topiramate capsule comprises 20 wt-% to 25 wt-% of one or more pore former(s), based on the total weight of the coating. 
     
     
         50 . The method of  claim 38  wherein the extended-release topiramate capsule comprises 10 wt-% to 20 wt-% of one or more plasticizer(s), based on the total weight of the coating.