Development of aqueous parenteral formulations for carbamazepine through the use of modified cyclodextrins.
The poor aqueous solubility of carbamazepine was dramatically increased via complexation with various chemically modified beta-cyclodextrins and gamma-cyclodextrins. A preparation of carbamazepine and 2-hydroxypropyl-beta-cyclodextrin was found to be stable to steam sterilization and to storage under a variety of conditions. Carbamazepine, when solubilized in this manner, was found to exert potent anticonvulsant effects in various seizure models and the formulation was tolerated in animals at high doses (100 mg/kg carbamazepine and 1200 mg/kg of the cyclodextrin excipient). The onset of anticonvulsant action was rapid and consistent with almost instantaneous in vivo complex dissociation. The low toxicity of 2-hydroxypropyl-beta-cyclodextrin, when administered via the parenteral route, and its ability to enhance the aqueous solubility of carbamazipine highly favor the use of this excipient.
Brewster
M E
ME
Pharmatec, Inc., Alachua, FL 32615.
Anderson
W R
WR
Estes
K S
KS
Bodor
N
N
D000818:Animals; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D008297:Male; D051379:Mice; D010592:Pharmaceutic Aids; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014867:Water / Q000737:chemistry
D003505:Cyclodextrins; D010592:Pharmaceutic Aids; D014867:Water; D002220:Carbamazepine