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Arzneimittelforschung 2011; 61(10): 566-570
DOI: 10.1055/s-0031-1300554
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Comparative in vitro dissolution and in vivo bioequivalence of two diclofenac enteric coated formulations

Saeed Basmenji
1   Daana Pharmaceutical Company, Tabriz, Iran
,
Hadi Valizadeh
2   Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
3   Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Parvin Zakeri-Milani
3   Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4   Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
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Publication History

Publication Date:
01 February 2012 (online)

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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 °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 AUCt 0 and AUC0 ∞ were 5726.1 (ng. h/ml) and 5917.8 (ng · h/ml) for the test and 5689.9 (ng · h/ml) and (ng · 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 t 0 (96.3–109.1%) and AUC ∞ 0 (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.

Key words

Bioavailability - Bioequivalence - Diclofenac - Dissolution
 

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