Pak. J. Pharm. Sci., Vol.29, No.5, September 2016, pp.1671-1679 1671 Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers Huma Ali 1,2 *, Muhammad Harris Shoaib 1 , Farya Zafar 2 , Muhammad Hanif 1 , Rabia Bushra 1 , Asia Naz 1 and Raheela Khursheed 2 1 Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan 2 Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan 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 µg.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 (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using Kinetica TM 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-∞ , 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-∞ (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. Keywords: Pharmacokinetics, Bioequivalence, Diclofenac Potassium, HPLC, validation, Compartmental and Non- Compartmental, Log and Non log transformed, INTRODUCTION Diclofenac potassium belongs to the category of non- steroidal anti-inflammatory drug (NSAID), it inhibits iso- forms of cyclo-oxygenase and decreases the synthesis of prostaglandins in the body which is responsible to produces pain and inflammation. It is used for the treatment of mild to severe pain (Mcneely and Goa, 1999), used as an antipyretic agent, particularly useful in the treatment of osteoarthritis and rheumatoid arthritis (Shah et al., 2012), migraine (Diener et al., 2006) and primary dysmenorrhea (Chang et al., 2002). Process of formulation development become challenging day by day and it is prerequisite to substantiate the formulation change with in vivo study to prove the validity of new formulation with respect to pharmacokinetics and its effectiveness. Today there has been significant application of pharmacokinetic investigations to explain various parameters in specific conditions and individualize the dose of the product (Abbas et al., 2013). Pharmacokinetic parameters are influenced by various factors particularly gastric residence time, volume and composition of gastrointestinal fluids, critical destructive forces during peristalsis and variations in absorption along the gastrointestinal tract (Kimura and Higaki, 2002; Fadda et al., 2010; Coupe et al., 1991). In case of any change in the composition of formulation, various pharmacokinetics investigations in healthy human volunteers are involved to develop bioequivalence with the reference formulation. Bioequivalence is the comparative evaluation between reference and test products to certify the relative bioavailability with exact criteria and particular defined objectives (Chen et al., 2009). The magnitude of bioequivalence studies is well growing over the couple of years due to the high volume of generic products in local markets and their extensive prescribing utilizations (Vetchy et al., 2007). Manufacturers required to conduct the bioequivalence studies to provide assurance for similar drug profiles of the generic version with original drug in bloodstream over time. Metabolic profiles can significantly modifies the pharmacokinetic parameters of the products, so bioequivalence assessment assist in the comparison of the metabolism of different drugs in various populations (Srinivas et al., 2009). Previously several methods were studied and reported for the assessment of diclofenac potassium in plasma by using LC-MS, HPTLC, spectroscopy, HPLC techniques, *Corresponding author: e-mail: humaali80@live.com