The favorable efficacy, toxicity and adverse side-effect profiles of carbamazepine (CBZ) contribute to its widespread and increasing use to control seizure in the epileptic patient. However, in cases when oral drug treatment is not feasible, no parenteral formulation is available for CBZ. Currently epileptic patients who are unable to maintain oral CBZ must be treated with other anticonvulsants formulated for parenteral administration. This multiple drug approach often leads to unpredictable seizure control and increased drug toxicity in chronically CBZ treated patients. Our preliminary studies showed first that aqueous solutions of CBZ can be given intravenously (i.v.). Second, anticonvulsant activity of CBZ is unaltered in the mouse MES (maximal electroconvulsant shock) model when given in the aqueous formulation. Third, the i.v. total daily dose of CBZ projected to maintain seizure control can be formulated in a reasonable volume. This approach to parenteral formulation of CBZ is based on using a water soluble excipient which is known to form an inclusion complex with lipophilic drugs. The excipient has a favorable toxicity profile for i.v. dosing and the solutions are stable to heat sterilization. The proposed studies examine the feasibility of developing a parenteral formulation of CBZ based on this patented inclusion complex technology. Studies will explore: formulation stability, compatibility with other i.v. fluids, venous irritation, toxicity profiles and manufacturing reproducability. Successful development of a CBZ formulation for i.v. administration would benefit the epileptic patient who is unable to maintain oral CBZ therapy.
