Preparation and In Vitro/In Vivo Evaluation of Puerarin Solid Self-Microemulsifying Drug Delivery System by Spherical Crystallization Technique.

Abstract

The aim of this work was to establish a method for preparing stable and controllable solid self-microemulsifying drug delivery system (S-SMEDDS) by spherical crystallization technique, which was explored for promoting the dissolution, oral bioavailability, and process efficiency. Solubility test, preparation of liquid self-microemulsifying drug delivery system (L-SMEDDS), and the obtained ternary phase diagrams test have been performed to screen and optimize the composition of LSMEDDS. The optimized formulation was used to prepare puerarin solid self-microemulsifying drug delivery system (Pue-SSMEDDS) by spherical crystallization technique. Droplet size and morphological analysis of the optimal Pue-SSMEDDS were determined to evaluate the final formulation. And the Pue-SSMEDDS was also assessed by flowability study, angle of repose, Carr's index, and flow velocity. Furthermore, the vitro dissolution and pharmacokinetic profile in vivo were analyzed. The study in vitro showed the Pue-SSMEDDS could disperse in the dispersion medium within 60s and was spherical with the particle size of 19.66nm and zeta potential of -28.3mV. It could keep stable at low temperature and seal condition for 3months. In vivo pharmacokinetic experiments of rats, the mean plasma concentration of self-microemulsion group was much higher than that of conventional tablets and could play a long-lasting efficacy, while there was no significant difference between the LSMEDDS and S-SMEDDS. The results suggested the potential of S-SMEDDS could improve the oral bioavailability of poorly water-soluble drug, such as puerarin.