Bioequivalence of Two Prolonged-Release Diclofenac Sodium Formulations in Healthy Volunteers: A Randomized, Crossover, Double-Blind Study

Background: The implementation of generic drug development programs constitutes a basic component of the global health policy. The aim of this work is to determine the existence of bioequivalence between two prolonged release diclofenac sodium formulations in healthy volunteers. Methods: A phase I, randomized, crossover, double-blind clinical trial was conducted where pharmacokinetics in plasma and biological safety of Voltaren Retard® (reference formulation) and a generic prolonged-release Cuban diclofenac sodium formulation were compared. The sampling period was 24 hours, with a washout time of 15 days between each one. All subjects received, orally, a single dose of 100 mg (one tablet) of the corresponding formulation in each period. Results: Thirty-six volunteers, the half women, with a mean age of 33 years were included. White skin subjects were 56%. The quantification of diclofenac sodium in plasma by HPLC demonstrated a high similitude between formulations. The mean values of the pharmacokinetic parameters were: AUC24 (4924 vs. 4928 ng.h/mL), AUCinf (5046 vs. 5054 ng.h/mL), Cmax (1047 vs. 1042 μg/mL), t1/2 2.25 vs. 2.25 h), Median Tmax was 2 hours for both formulations. The preparations could be considered as bioequivalent according to ANOVA and 90% CI analysis. No formulation, period, sequential and residual effects were detected. The adverse events were mild, well tolerated, with a low frequency of onset. The most frequent events were hypertension, headache and increase in transaminases and urea values, registered in less than 10% of the subjects. Conclusion: Cuban prolonged-release diclofenac sodium formulation was bioequivalent with the commercial reference formulation Voltaren Retard®.