Bioequivalence study of Naproxen sodium tablet 220 mg (test) vs reference tablet containing Naproxen sodium 220 mg in healthy adult human volunteer under fasting condition

Abstract

ABSTRACT Aim & Objective: Naproxen is non steroidal anti inflammatory drugs (NSAIDS) which is used for its antipyretic and analgesic activity. Naproxen is given for multiple actions orally. It is used in pain, fever, and inflammation. This study was performed to compare the bioequivalence of a locally made oral tablet (test product) of naproxen with innovators product (reference) by using data from plasma naproxen concentration. Materials and methods: Twenty four healthy volunteers were selected, after screening, in the study. The study was a randomized, open label, balanced, two treatment, two periods, two sequence, single dose, crossover, design bioequivalence study, with a one week wash-out period. A single 220 mg naproxen sodium tablet of either the reference product or the test product was orally administered to each subject. A venous blood sample of five ml was drawn prior to dosing and at different time points intervals up to 72 hours after dosing. LC-MS/MS was used to analyze the plasma sample for total naproxen concentration. Result: The results showed that naproxen concentration (Cmax) of all subjects was found to be 51.07 ± 10.00 and 58.7 0 ± 7.89 ng/ml in test and reference product, respectively. Area under the plasma concentration time profile curve from time zero to last time (AUC0-72) was 646.27 ± 132.91and 658.38 ± 19.63 (ng.h/ml) in test and reference product, respectively. Mean time to reach maximum plasma concentration Tmax was 72.00 ± 15.13 and 3.00 ± 0.81 hrs in test and reference product respectively. The results for C max values for Naproxen Test A (mean 39.83 ng/ml, SD 10.0 % CV 25.10), and for Reference – B (mean 41.83 SD 7.89 %CV 18.86) showed that the time to reach the peak concentration was not similar for test product as well as the reference product. The half-life (T1/2) value for naproxen sodium Test – A (mean 23.90, SD 7.69, %CV 18.44) and for Reference – B (mean 18.54, SD 4.78, %CV 25.76) were not same for Test and Reference drugs formulations. The 90% confidence interval for the log transformed ratio (Test/Reference) for the mean Cmax of the Naproxen sodium was 65.92% to 114.55% (Range: 80% to 125%) and that for the mean AUC(0-t) was 67.71% to 108.68% (Range: 80% to 125%). The mean Cmax, AUC (0-t), and Tmax between the two products were statistically different.