Comparative bioavailability study of a conventional and two controlled release oral formulations of Tegretol (carbamazepine)--200 mg

Abstract

Objectives: To assess the bioquivalence of carbamazepine (CBZ) controlled release formulation A (Tegretol CR, local) vs formulation B (Tegretol CR, Basel) and confirm their controlled release characteristics by comparing with conventional formulation (Tegretol).

Methods: A three-way randomized cross-over bioavailability study was carried out using CBZ 200 mg tablets of conventional and two controlled release formulations in twelve healthy volunteers. Coded plasma samples were analysed for levels of CBZ by HPLC method.

Results: The mean Cmax, Tmax, t1/2 and AUC for formulation A were: 1.67 +/- 0.26 mcg/mL, 24 +/- 0 hr, 47.8 +/- 9.7 hr and 136.7 +/- 25.4 mcg/ml. h; for formulation B were 1.41 +/- 0.31 mcg/mL, 25 +/- 8 hr, 46.9 +/- 7.9 and 119 +/- 32.3 mcg/ml.h and for conventional formulation were 2.43 +/- 3.6 mcg/mL, 9.5 +/- 7.4 hr, 44.6 +/- 9.8 hr and 178.8 +/- 41.9 mcg/ml.h respectively. The fluctuation in plasma concentration within 24 h (peak:trough) were 11.7 +/- 8.14% with conventional formulation as compared to 0% and 1.2 +/- 3.98% with formulation A and B respectively. The mean Tmax for both the controlled release formulations was not statistically significant. On the basis of 90% confidence interval, mean AUC and Cmax values obtained after controlled release formulation A, though statistically significant (P < 0.05) lie well within the prescribed limits of 80-120% as compared to formulation B. Thus both the controlled release formulations were bioequivalent. In comparison to conventional formulation, both controlled release formulations gave lower Cmax, lower AUCs, higher Tmax values, less fluctuation in CBZ plasma concentrations, reduction in ratio of Cmax/AUC values, thus demonstrating controlled release characteristics of the formulation.

Conclusions: Based on the above mentioned parameters both controlled release formulations are bioequivalent and demonstrate controlled release characteristics.