Novel parenteral carbamazepine formulation

Abstract

The present invention is directed to a carbamazepine-cyclodextrin inclusion complex useful for the parenteral administration of carbamazepine. The carbamazepine-cyclodextrin inclusion complex is prepared by the admixture of a modified cyclodextrin and carbamazepine in a physiologically acceptable fluid. Modified cyclodextrins include 2-hydroxypropyl-beta-cyclodextrin and sulfoalkyl cyclodextrins. More particularly, the sulfoalkyl cyclodextrins are those described and disclosed in U.S. Pat. Nos. 5,134,127 and 5,376,645. A physiologically acceptable fluid includes sterile isotonic water, Ringer's lactate, D5W (5% dextrose in water), physiological saline, and similar fluids suitable for parenteral administration.

We claim: 
     
         1 . An injectable pharmaceutical composition comprising
 i. about 10 mg/mL of carbamazepine,   ii. about 25% weight/volume of a sulfoalkyl-cyclodextrin, and   iii. a physiologically acceptable fluid,   wherein said composition is administered parenterally, and   wherein said composition contains carbamazepine in a dose of about 30% to about 100% of a patient's oral maintenance dose.   
     
     
         2 . The composition of  claim 1 , wherein the sulfoalkyl-cyclodextrin is sulfobutylether-7-β-cyclodextrin. 
     
     
         3 . The composition of  claim 1 , wherein administration is intravenous, intraarterial, intramuscular, subcutaneous or intraperitoneal. 
     
     
         4 . The composition of  claim 1 , wherein administration is intravenous. 
     
     
         5 . The composition of  claim 1 , wherein said composition contains carbamazepine in a dose of about 65% to about 75% of a patient's oral maintenance dose. 
     
     
         6 . The composition of  claim 1 , wherein said composition provides an AUC for carbamazepine from about 70% to about 130% of the AUC for carbamazepine in the oral maintenance dose. 
     
     
         7 . The composition of  claim 1 , wherein said composition provides a minimum plasma concentration of about 70% to about 130% of the minimum carbamazepine plasma concentration of the oral maintenance dose. 
     
     
         8 . The composition of  claim 1 , wherein said composition provides a minimum plasma concentration of about 80% to about 125% of the minimum carbamazepine plasma concentration of the oral maintenance dose. 
     
     
         9 . The composition of  claim 1 , wherein said composition provides trough carbamazepine concentrations within the therapeutic range. 
     
     
         10 . The composition of  claim 1 , wherein said composition provides a carbamazepine half-life of about 8 to about 65 hours. 
     
     
         11 . The composition of  claim 1 , wherein said composition provides a carbamazepine half-life of about 24 hours. 
     
     
         12 . The composition of  claim 1 , wherein said composition has a dosing interval of every 6 hours. 
     
     
         13 . An injectable pharmaceutical composition comprising
 i. about 10 mg/mL of carbamazepine,   ii. about 25% weight/volume sulfobutylether-7-β-cyclodextrin, and   iii. a physiologically acceptable fluid,   wherein said composition is administered intravenously, and   wherein said composition contains carbamazepine in a dose of about 30% to about 100% of a patient's oral maintenance dose.   
     
     
         14 . The composition of  claim 13 , wherein said composition contains carbamazepine in a dose of about 65% to about 75% of a patient's oral maintenance dose. 
     
     
         15 . The composition of  claim 13 , wherein said composition provides an AUC for carbamazepine from about 70% to about 130% of the AUC for carbamazepine in the oral maintenance dose. 
     
     
         16 . The composition of  claim 13 , wherein said composition provides a minimum plasma concentration of about 70% to about 130% of the minimum carbamazepine plasma concentration of the oral maintenance dose. 
     
     
         17 . The composition of  claim 13 , wherein said composition provides a minimum plasma concentration of about 80% to about 125% of the minimum carbamazepine plasma concentration of the oral maintenance dose. 
     
     
         18 . The composition of  claim 13 , wherein said composition provides trough carbamazepine concentrations within the therapeutic range. 
     
     
         19 . The composition of  claim 13 , wherein said composition provides a carbamazepine half-life of about 8 to about 65 hours. 
     
     
         20 . The composition of  claim 13 , wherein said composition provides a carbamazepine half-life of about 24 hours. 
     
     
         21 . The composition of  claim 13 , wherein said composition has a dosing interval of every 6 hours. 
     
     
         22 . An injectable pharmaceutical composition comprising
 i. about 10 mg/mL of carbamazepine,   ii. about 25% weight/volume sulfobutylether-7-β-cyclodextrin, and   iii. a physiologically acceptable fluid,   wherein said composition is administered intravenously,   wherein said composition contains carbamazepine in a dose of about 65% to about 75% of a patient's oral maintenance dose, and   wherein said composition provides a minimum plasma concentration of about 70% to about 130% of the minimum carbamazepine plasma concentration of the oral maintenance dose.   
     
     
         23 . The composition of  claim 22 , wherein said composition provides an AUC for carbamazepine from about 70% to about 130% of the AUC for carbamazepine in the oral maintenance dose. 
     
     
         24 . The composition of  claim 22 , wherein said composition provides an AUC for carbamazepine from about 80% to about 125% of the AUC for carbamazepine in the oral maintenance dose. 
     
     
         25 . The composition of  claim 22 , wherein said composition provides a minimum plasma concentration of about 80% to about 125% of the minimum carbamazepine plasma concentration of the oral maintenance dose. 
     
     
         26 . The composition of  claim 22 , wherein said composition provides trough carbamazepine concentrations within the therapeutic range. 
     
     
         27 . The composition of  claim 22 , wherein said composition provides a carbamazepine half-life of about 8 to about 65 hours. 
     
     
         28 . The composition of  claim 22 , wherein said composition provides a carbamazepine half-life of about 24 hours. 
     
     
         29 . The composition of  claim 22 , wherein said composition has a dosing interval of every 6 hours. 
     
     
         30 . An injectable pharmaceutical composition comprising
 i. about 10 mg/mL of carbamazepine,   ii. about 25% weight/volume sulfobutylether-7-β-cyclodextrin, and   iii. a physiologically acceptable fluid,   wherein said composition is administered intravenously,   wherein said composition contains carbamazepine in a dose of about 65% to about 75% of a patient's oral maintenance dose,   wherein said composition provides a minimum plasma concentration of about 70% to about 130% of the minimum carbamazepine plasma concentration of the oral maintenance dose,   wherein said composition provides an AUC for carbamazepine from about 70% to about 130% of the AUC for carbamazepine in the oral maintenance dose, and   wherein said composition provides trough carbamazepine concentrations within the therapeutic range.