In Vitro-In Vivo Correlation for Solid Dispersion of a Poorly Water-Soluble Drug Efonidipine Hydrochloride.

Abstract

The aim of this present study was to investigate the ability of different dissolution methods to predict the in vivo performance of efonidipine hydrochloride (EFH). The solid dispersions of EFH were prepared by solvent evaporation method with HPMC-AS as matrix and urea as a pH adjusting agent. The paddle method, the open-loop, and the closed-loop flow-through cell methods were studied. In the study, Weibull's model was the best fit to explain release profiles. The pharmacokinetics behaviors of two kinds of solid dispersions with different release rate were investigated in comparison to the EFH after oral administration in rats. In vivo absorption was calculated by a numerical deconvolution method. In the study, the level A in vivo and in vitro correlation (IVIVC) was utilized. The correlation coefficient was calculated and interpreted by means of linear regression analysis (Origin.Pro.8.5 software). As a result, excellent IVIVC for solid dispersions and crude drug (r2 = 0.9352-0.9916) was obtained for the dissolution rate determined with flow-through cell open-loop system in phosphate buffer solution with 0.1% (w/v) polysorbate 80 at pH 6.5, the flow-rate of 4mL/min. In addition, the self-assembled flow cell system had good repeatability and accuracy. The dissolution rate of the solid dispersion could be slowed down by the flow-through method, and the difference caused by preparation was significantly distinguished. The study demonstrated that flow-through cell method of the open-loop, compared with paddle method, was suitable for predicting in vivo performance of EFH solid dispersions.