Comparative studies of bioavailability of naproxen tablets commercially available in Thailand

Abstract

Naproxen tablets commercially available in Thailand were investigated in order to assess the bioequivalence of the local manufactured brands relatively to the original brand, Naprosyn. These tablets were evaluated both in vitro and in vivo. The in vitro studies included the content of active ingredient, hardness, disintegration time and dissolution rates in both simulated gastric fluid and simulated intestinal fluid. The content of active ingredient of all brands were within the range of limitation as specified by the United Stated Pharmacopoeia XXI monograph. The hardness of tablet ranged from 4.52 ± 0.39 to more than 20 kp., and statistically significant differences among all brands were observed (p < 0.05) . All nine brands of naproxen tablets met the United State Pharmacopoeia XXI specification for disintegration time, within 30 minutes, however they were statistically significant differences (p < 0.05) . The dissolution rate constants of these nine brands in simulated gastric fluid and simulated intestinal fluid ranged from 0.55 ± 0.09 to 2.03 ± 0.35 hour and 0.76 ± 0.20 to 6.22 ± 1.96 hour , respectively. Statistical results of dissolution rate constants showed significant differences (p < 0.05) between brand A and B, D, E, H, I in simulated gastric fluid and between brand A and brands B, D, H, I in simulated intestinal fluid. The bioavailability of five brands of naproxen tablets with differences using a crossover experiment. A single dose of 250 mg. naproxen tablet was orally administered to individual overnight fasted subjects. Plasma naproxen levels were determined by a specifically high performance liquid chromatographic method. Individual plasma-time profile was analyzed according to noncompartmental method. Results showed that no statistically significant differences (p < 0.05) in both the rate and the extent of naproxen absorption among the five brands studied were observed. These indicated that the four local manufactured brands of naproxen tablets were bioequivalent to the original brand. There were no statistically significant linear correlation between hardness, and disintegration time of dissolution rates in both dissolution media of all brands studied (p < 0.05) . The disintegration time and the in vivo parametters (AUC∞₀, Ka, Cpₘₐₓ Tₘₐₓ) Were not correlated (p < 0.05) . The dissolution rate constants in both dissolution media and the in vivo parameters (AUC∞₀, Ka, Cpₘₐₓ Tₘₐₓ) were not significantly correlative as well (p < 0.05) .