Stabilized pediatric suspension of carisbamate

Abstract

The present invention provides a stabilized pharmaceutical suspension of carisbamate for pediatric and adult use. More particularly, the suspension is stabilized with hypromellose (HPMC) to prevent crystal growth of the suspended particles and to prevent re-crystallization of the drug product with change in polymorphic form.

1 - 6 . (canceled) 
     
     
         7 . A method of treating a disorder selected from the group consisting of epilepsy, neuropathic pain, tremor, epileptogenesis, neuroprotection, schizophrenia, non-schizophrenic psychoses, dementia, behavioral disturbances in mental retardation and autism, bipolar mania, depression, and anxiety, in a mammal in need thereof, which comprises
 administering to the mammal a therapeutically-effective amount of a pharmaceutical composition in the form of a stabilized aqueous suspension,   wherein the stabilized aqueous suspension comprises a) from about 10 to about 30 mg/ml carisbamate; b) from about 5.0 to about 15.0 mg/ml of hypromellose; and c) water, and   wherein the therapeutically-effective amount of carisbamate is administered in a total daily dose ranging from 50 mg to 1,200 mg.   
     
     
         8 . The method of  claim 7 , wherein said disorder is epilepsy. 
     
     
         9 . The method of  claim 8 , wherein the method comprises administering to a pediatric patient. 
     
     
         10 . The method of  claim 7 , wherein said disorder is neuropathic pain. 
     
     
         11 . The method of  claim 7 , wherein the pharmaceutical composition further comprises one or more agents selected from the group consisting of a suspending agent, a wetting agent, a preservative agent, a buffering agent, a sweetening agent, and a flavoring substance. 
     
     
         12 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a suspending agent. 
     
     
         13 . The method of  claim 12 , wherein the suspending agent is selected from the group consisting of methyl cellulose, sodium carmellose, hypromellose, polyvinylpyrrolidone, alginate, chitosan, dextran, gelatin, polyethylene glycol, polyoxyethylene ether and polyoxypropylene ether. 
     
     
         14 . The method of  claim 12 , wherein the suspending agent includes microcrystalline cellulose and sodium carmellose. 
     
     
         15 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a wetting agent. 
     
     
         16 . The method of  claim 15 , wherein the wetting agent is selected from the group consisting of polysorbate 20, polysorbate 80, lecithin, polyoxyethylene ethers, polyoxypropylene ether, and sodium deoxycholate. 
     
     
         17 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a preservative agent. 
     
     
         18 . The method of  claim 17 , wherein the preservative agent is selected from the group consisting of benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorbutol, gallate, hydroxybenzoate and EDTA. 
     
     
         19 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a buffering agent. 
     
     
         20 . The method of  claim 19 , wherein the buffering agent is citric acid monohydrate. 
     
     
         21 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a sweetening agent. 
     
     
         22 . The method of  claim 21 , wherein the sweetening agent is selected from the group consisting of sucralose, saccharin, sodium saccharin, potassium saccharin, calcium saccharin, acesulfame potassium, sodium cyclamate, mannitol, fructose, sucrose, and maltose. 
     
     
         23 . The method of  claim 7 , wherein the pharmaceutical composition further comprises a flavoring substance. 
     
     
         24 . The method of  claim 23 , wherein the pharmaceutical composition further comprises sodium benzoate, citric acid monohydrate, microcrystalline cellulose and sodium carmellose. 
     
     
         25 . The method of  claim 7 , wherein the pharmaceutical composition comprises about 20 mg/ml carisbamate, about 1.18 mg/ml sodium benzoate, about 1.3 mg/ml citric acid monohydrate, about 13 mg/ml microcrystalline cellulose and sodium carmellose, and about 10 mg/ml hypromellose. 
     
     
         26 . The method of  claim 25 , wherein the pharmaceutical composition further comprises about 4 mg/ml sucralose. 
     
     
         27 . The method of  claim 7 , wherein the hypromellose stabilizes the crystal structure and/or maintains polymorphic form of carisbamate. 
     
     
         28 . The method of  claim 7 , wherein the pharmaceutical composition is administered to a pediatric patient. 
     
     
         29 . A pharmaceutical composition in the form of aqueous suspension comprising:
 a) from about 10 to about 30 mg/ml carisbamate;   b) from about 5.0 to about 15.0 mg/ml of hypromellose; and   c) water.