Comparative Bioavailability of Diclofenac Sodium Enteric-Coated tablets commercially available in Thailand

Abstract

Eight brands of 25 mg. diclofenac socium enteric-coated tablet were evaluated. In vitro studies indicated that all brands except brand F, met the requirement of the USP XXII for disintegration of enteric-coated tablets. The dissolution rate constants of all brands in simulated intestinal fluid TS without enzyme (pH 7.5±0.1) ranged from 0.06 to 0.22 min.⁻¹. The value of brand A, which was the innovator’s product, showed statistically significant (p<0.05) higher than those of brands C, D, E and H. The comparative bioavailability of four brands of diclofenac sodium enteric-coated tablet with difference in dissolution properties were studied in 12 healthy Thai male subjects using a single dose of two 25 mg. tablets in a crossover design. Plasma diclofenac sodium concentrations were determined via HPLC technique. Individual plasma concentration-time profile was analyzed for relevant pharmacokinetic parameters. Data analysis revealed that there were no statistically significant differences (p>0.05) for the C[subscript max], t[subscript max] and AUC values. These implied that all four brands were bioequivalent with each other. The relative bioavailability or brands B, E and H with respect to brand A were 114.91, 112.26 and 98.80%, respectively. Correlative studies between the invitro and the in vivo data indicated that the disintegration time exhibited statistically significant correlation with the C[subscript max] meanwhile the dissolution rate constants were correlative with the t[subscript max]. This meant that the in-vitro data could be used to predict the bioavailability of diclofenac sodium enteric-coated tablet with respect to only the rate of drug absorption into systemic circulation. The pharmacokinetic of diclofenac sodium enteric-coated tablet was well described by one compartment open model. The absorption rate constants ranged from 0.9085 to 1.8850 hr. ⁻¹. The biological half-lives varied between 1.40 to 2.52 hr.