Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets

Abstract

The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi-Fickian diffusion-based release mechanism. The C_max, t_max, mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower C_max, similar t_max, and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern.

Keywords::

• In vitro release
• pharmacokinetics
• beagle dogs
• nimesulide
• bilayer tablet
• fast release
• sustained release

Acknowledgments

The valuable technical assistance and discussion of F.H. Meng is gratefully acknowledged.

Declaration of interest

This work was supported by the National Key Technologies R&D Program for New Drugs (Grant no. 2009ZX09301-002, 2008ZXJ09010-001).