title: Comparative in vitro dissolution and in vivo bioequivalence of two diclofenac enteric coated formulations.
abstract: 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.
authors.affiliation: Daana Pharmaceutical Company, Tabriz, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Basmenji
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
mesh_terms: D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D016037:Single-Blind Method; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013608:Tablets, Enteric-Coated; D004008:Diclofenac