Comparative in vitro Dissolution and in vivo Bioavailability of Diflunisal/Naproxen Fixed-Dose Combination Tablets and Concomitant Administration of Diflunisal and Naproxen in Healthy Adult Subjects

S. A. Helmy; H. M. El Bedaiwy

doi:10.1055/s-0033-1333768

Drug Research, Table of Contents

Drug Res (Stuttg) 2013; 63(03): 150-158
DOI: 10.1055/s-0033-1333768

Original Article

Comparative in vitro Dissolution and in vivo Bioavailability of Diflunisal/Naproxen Fixed-Dose Combination Tablets and Concomitant Administration of Diflunisal and Naproxen in Healthy Adult Subjects

Authors

S. A. Helmy

¹Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
H. M. El Bedaiwy

²Department of Industrial Pharmacy, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

Abstract

A simple validated high-performance liquid chromatography (HPLC) assay was developed for determination of diflunisal and naproxen in human plasma samples. This is to compare the bioavailability of diflunisal-naproxen fixed-dose combination (FDC) with their separate dosage forms. The in vitro dissolution study was adopted to compare the dissolution behavior of FDC with respect to separate marketed tablets. In vivo study was conducted according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 10 days. Under fasting conditions, 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either one FDC tablet or co-administration of two separate diflunisal and naproxen marketed tablets. Plasma samples were obtained over a 72-h interval and analyzed for diflunisal and naproxen by reversed phase liquid chromatography with UV detection. The pharmacokinetic parameters C_max, AUC_0-t, AUC_0-∞, t_max, and t_1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of C_max, AUC_0-t, and AUC_t-∞ of the 2 treatments were within the acceptable range (0.8–1.25) for bioequivalence. From pharmacokinetic and in vitro studies perspectives, 1 FDC tablet demonstrated similar relative bioavailability with the 2 individual reference tablets.

Key words

diflunisal - naproxen - dissolution - pharmacokinetics - bioavailability - HPLC

Full Text

References

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