Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets [50mg] in healthy volunteers

ABSTRACT

This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test [F4] tablet formulation with reference product [Caflam]. Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 [micro]g.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points [0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test [F4] and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples [20[micro]L] were injected using the validated HPLC method. Various pharmacokinetic parameters [compartmental and noncompartmental] were estimated using KineticaTM 4.4.1 [Thermo Electron Corp. USA]. Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for C[maxcalc], T[maxcalc], AUC[0-[infinity]], AUC[tot] and AUC[last] using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC[0-[infinity]] [0.997-1.024], AUC[tot] [1.004-1.031], AUC[last] [0.997 - 1.024], C[maxcalc] [0.994-1.007] and T[maxcalc] [0.996-1.013] for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated