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

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.

Bioequivalence studies of celiprolol in healthy human volunteers.

Thus bioequivalence between the two products was established by undertaking this study. From table 1 it can be seen that the standard deviation at the various sampling points is high indicating varying absorption rates in individual volunteers, but this was observed in case of both the products. Also, since the study design was complete crossover, this high standard deviation was not due to any study design variable. As celiprolol shows non-linear1 dose related absorption kinetics this high value of standard deviation may be due to the intersubject variation during the absorption process. However all the pharmacokinetic parameters showed a comparable profile when statistically evaluated for any significant difference between the two products.