Comparative bioavailability of glibenclamide tablets

Abstract

Seven brands of 5 mg. glibenclamide tablets were evaluated. The in vitro studies indicated that all brands met the requirements of the British Pharmacopoeia 1988. The dissolution rate constants of all brands in simulated intestinal fluid TS without enzyme (pH 7.5 ± 0.1) ranged from 0.68 to 1.14 hr-1. The value of dissolution rate constant of brand A, which was the innovator's product, showed statistically significance (p < 0.05) higher than those from brand B, C, E, F and G, but showed no statistically significance to brand D. The bioavailability of four brands of glibenclamide tablet with difference in dissolution rate constants were studied in Thai healthy male subjects using, a single dose of 5 mg. in a crossover design. Plasma glibenclamide concentrations were determined via HPLC technique. Data analysis by CSTRIP computer program revealed that there were no statistically significant difference (p > 0.05) for the tmax values among the four brands except for the Cmax and AUC values. The results imply the bioequivalency between brand A and brand D. The relative bioavailability with respect to brand A for brands C, D and F were 67.16, 104.09 and 82.95% respectively. Pharmacokinetics of glibenclamide tablet was well described by one-compartment open model with lag time. The absorption rate constants ranged from 0.75 to 0.92 hr-1. The elimination rate constants ranged from 0.24 to 0.29 hr-1. The biological half-life varied between 2.46 to 3.18 hr. Correlation studies between the in vitro and the in vivo data indicated that the disintegration time exhibited statistically significant correlation with only the Cmax meanwhile the dissolution rate constants were highly correlative with both the Cmax and the AUC.