Pharmacokinetic Parameters Determination and In Vitro-In Vivo Correlation of Ileocolonic-Targeted pH-Responsive Coated Mini-Tablets of Naproxen

Abstract

This research work aims to determine the pharmacokinetic parameters and in vitro-in vivo correlation of the selected ileocolonic-targeted coated mini-tablet filled capsule formulation of naproxen. The pure suspension and coated mini-tablet filled capsule formulation of naproxen were administered to adult albino rabbits through the oral route. The samples were analyzed for naproxen by an HPLC method. For the pure drug suspension, the peak plasma concentration was found as 8.499±0.029 μg/ml at 1.139±0.010 hours and the half-life was found to be 9.459±0.387 hours, whereas for the formulation the peak plasma concentration was found as 6.814±0.037 μg/ml at 8.042±0.069 hours and the half-life was found to be 19.657±0.359 hours. This decreased the peak plasma concentration at a delayed time and increased the half-life of the capsule formulation in comparison with the pure drug suspension which showed that naproxen was only targeted to the ileocolonic region. A significant in vitro-in vivo correlation (i.e. R(2)=0.9901) was also obtained. Thus, the results of these findings suggest that naproxen formulated as coated mini-tablets can be suitable for targeted ileocolonic drug delivery.

Keywords: Coated-mini-tablets; Eudragit L100; Eudragit S100; Naproxen; Rabbits.

Fig. 1

In vitro dissolution profile of the optimized coated mini-tablet filled capsule formulation of naproxen (mean ± SD; n=3)

Fig. 2

Mean plasma concentrations level versus time profile curve of naproxen after administration of 16.666 mg of the oral dose for both the treatments (mean ± SD; p < 0.05; n=3)

Fig. 3

In vitro percent of naproxen released versus in vivo percent naproxen absorbed