Parenteral carbamazepine formulation
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.
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 human'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 the human'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 human'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 the human'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 human'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 human'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.