The aim of this study was the comparison of in vitro dissolution and in vivo bioavailability of two different brands of diclofenac sodium (CAS 15307-86-5) enteric coated tablets in healthy male Iranian volunteers in a single-dose, randomized, open-label, single blind study, which was conducted according to a crossover design in healthy volunteers. A washout interval of two weeks was selected between administrations to each subject in this study. Serial venous blood samples over 10 h after each administration to measure diclofenac sodium concentration in serum were obtained, and placed into tubes containing sodium heparin. Then the plasma was separated and kept frozen at -20 degrees C for subsequent analysis with a modified HPLC method with UV detection. In addition, the in vitro dissolution study was performed on the brands. For the test and reference formulation, mean Cmax values were 2257.3 (ng/ml) and 2156 (ng/ml), respectively. The mean AUC(0)tau and AUC(0)infinity were 5726.1 (ng x h/ml) and 5917.8 (ng x h/ml) for the test and 5689.9 (ng x h/ml) and 5967.4 (ng x h/ml) for the reference formulation, respectively. Results show that the 90% confidence intervals for the ratio of test and reference products in Cmax (101.4-114.9%), AUC(0)tau (96.3-109.1%) and AUC(0)infinity (94.7-107.3%) were all within the 80-125% interval proposed by the FDA and EMA. Both formulations released > 80% of drug within 30 min in buffer pH = 6.8 medium. Therefore the diclofenac sodium enteric coated tablets of the test and reference formulations are bioequivalent in terms of rate and extent of absorption.

Based on the 90% CIs of Cmax, AUC0-t and AUC0-∞ in these healthy Iranian male subjects, the test and reference formulations of betamethasone injectable suspension met the regulatory requirements for bioequivalence.