Oral pharmaceutical composition comprising zonisamide and process of preparation thereof

Abstract

The present invention relates to the pharmaceutical composition comprising Zonisamide and one or more pharmaceutically acceptable excipients and also relates to the process for the preparation of the pharmaceutical composition comprising Zonisamide.

1 . A liquid oral pharmaceutical suspension, comprising:
 zonisamide in an amount of about 20 mg/mL;   a suspending agent;   one or more vehicles; and   one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise one or more buffering agents;   wherein the liquid oral pharmaceutical suspension has a pH of 3.5 to 5.0, wherein the liquid oral pharmaceutical suspension is stable for at least 6 months when stored at 40° C. and 25% relative humidity.   
     
     
         2 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the suspending agent comprises sodium alginate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), microcrystalline cellulose, tragacanth, xanthan gum, bentonite, carageenan, guar gum, colloidal silicon dioxide, or any combination thereof. 
     
     
         3 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the suspending agent comprises sodium alginate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), microcrystalline cellulose, tragacanth, xanthan gum, or any combination thereof. 
     
     
         4 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the suspending agent comprises gelatin, crosslinked polyacrylic acid, polymethacrylic acid, polyhydroxyethyl methacrylic acid, hydroxypropyl methyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, hyaluronic acid, chitosan, polycarbophil, pectin, copolymers of dextran, polyacrylamide,  acacia , copolymer of caprolactone and ethylene oxide, carbopol 934, tragacanth, eudragit, polyvinyl pyrrolidone, polyacrylate and polyacrylate copolymer resins, hydroxyalkyl-celluloses, xanthan gum, polyvinyl resins, polyethylene glycol, sodium alginate, or any combination thereof. 
     
     
         5 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the suspending agent is present in the liquid oral pharmaceutical suspension at about 3 mg/mL to about 3.5 mg/mL. 
     
     
         6 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the one or more buffering agents are selected from the group consisting of sodium acetate, sodium citrate, ammonium sulfate, sodium phosphate, disodium hydrogen phosphate, potassium citrate, citric acid monohydrate, trisodium citrate dihydrate, and any combination thereof. 
     
     
         7 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the one or more buffering agents comprise citric acid monohydrate or tri-sodium citrate dihydrate. 
     
     
         8 . The liquid oral pharmaceutical suspension of  claim 1 , further comprising one or more sweetening agents, one or more flavoring agents, or any combination thereof. 
     
     
         9 . The liquid oral pharmaceutical suspension of  claim 8 , wherein the one or more sweetening agents are selected from the group consisting of sucralose, sucrose, glycerol, liquid glucose, sorbitol, maltitol, saccharin sodium, aspartame, and any combination thereof. 
     
     
         10 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the one or more vehicles are aqueous vehicles selected from the group consisting of purified water, hydro-alcoholic, a polyhydric alcohol, and any combination thereof. 
     
     
         11 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the one or more vehicles consist of water. 
     
     
         12 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the liquid oral pharmaceutical suspension has a single max impurity of 0.06% or less and total impurities of 0.10% or less. 
     
     
         13 . The liquid oral pharmaceutical suspension of  claim 1 , wherein the liquid oral pharmaceutical suspension exhibits less than 0.05% of impurity A and less than 0.25% of total impurity. 
     
     
         14 . A method of treating seizures in a subject in need thereof, comprising administering to the subject a liquid oral pharmaceutical suspension comprising:
 zonisamide in an amount of about 20 mg/mL;   a suspending agent;   one or more vehicles; and   one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise one or more buffering agents;   wherein the liquid oral pharmaceutical suspension has a pH of 3.5 to 5.0, wherein the liquid oral pharmaceutical suspension is stable for at least 6 months when stored at 40° C. and 25% relative humidity.   
     
     
         15 . The method of  claim 14 , wherein the subject has trouble swallowing a solid oral dosage form. 
     
     
         16 . The method of  claim 14 , wherein the liquid oral pharmaceutical suspension is used as an adjunctive therapy in the treatment of partial seizures in adults with epilepsy. 
     
     
         17 . The method of  claim 14 , wherein the suspending agent comprises sodium alginate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), microcrystalline cellulose, tragacanth, xanthan gum, or any combination thereof. 
     
     
         18 . The method of  claim 14 , wherein the suspending agent is present in the liquid oral pharmaceutical suspension at about 3 mg/mL to about 3.5 mg/mL. 
     
     
         19 . The method of  claim 14 , wherein the one or more buffering agents are selected from the group consisting of sodium acetate, sodium citrate, ammonium sulfate, sodium phosphate, disodium hydrogen phosphate, potassium citrate, citric acid monohydrate, trisodium citrate dihydrate, and any combination thereof. 
     
     
         20 . The method of  claim 14 , wherein the one or more buffering agents comprise citric acid monohydrate or tri-sodium citrate dihydrate. 
     
     
         21 . The method of  claim 14 , wherein the liquid oral pharmaceutical suspension further comprising one or more sweetening agents, one or more flavoring agents, or any combination thereof. 
     
     
         22 . The method of  claim 21 , wherein the one or more sweetening agents are selected from the group consisting of sucralose, sucrose, glycerol, liquid glucose, sorbitol, maltitol, saccharin sodium, aspartame, and any combination thereof 
     
     
         23 . The method of  claim 14 , wherein the one or more vehicles are aqueous vehicles selected from the group consisting of purified water, hydro-alcoholic, a polyhydric alcohol, and any combination thereof. 
     
     
         24 . The method of  claim 14 , wherein the one or more vehicles consist of water. 
     
     
         25 . The method of  claim 14 , wherein the liquid oral pharmaceutical suspension has a single max impurity of 0.06% or less and total impurities of 0.10% or less. 
     
     
         26 . The method of  claim 14 , wherein the liquid oral pharmaceutical suspension exhibits less than 0.05% of impurity A and less than 0.25% of total impurity.