In vitro disintegration and dissolution and in vivo bioequivalence of two alendronate once-weekly formulations

Abstract

Bioequivalence of two tablet formulations of 70 mg alendronate (CAS 121268-17-5) was assessed in a single-dose, open-label, randomised, fasted state crossover trial, with a washout period of 21 days, in 80 healthy subjects. Urine samples were collected up to +36 h post dosing and the concentrations of alendronic acid were assessed using a high-performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The 90 % confidence intervals (90 % CI) obtained for Ae0-36 (cumulative urinary excretion) and Rmax (maximum rate of urinary excretion) were 98.67-118.99 % and 102.22-122.46 %, respectively. The intra-subject coefficient of variation was between 32-35 % for both parameters. No relevant tolerability problems were detected. Both formulations can be considered bioequivalent. In vitro testing was performed to confirm the adequacy of the quality control conditions and no significant differences were detected neither in the disintegration test nor in the dissolution tests conducted in HCl 0.1 N and H2O and thus in these conditions the lack of statistically significant differences in vitro was accompanied by in vivo bioequivalence.