Comparison of different methods for preparation of a stable riccardin D formulation via nano-technology

Abstract

Riccardin D is a new compound extracted from liverwort Marchantia polymorpha L. It has been proved to be useful in antifungal therapy and reversing the resistance of Candida albicans against fluconazole. However, the poor solubility leads to the poor bioavailability and limits its development. In this study, nanocrystals were prepared in the evaporative precipitation into aqueous solution (EPAS) and the microfluidisation process. The characterizations of nanocrystals were compared by transmission electron microscope, size distribution, and zeta potential. In the EPAS method, the drug was dissolved in the organic phase and F68, HPMC, PVP K30 were dissolved in water with the mass ratio of 2:1:2:1. In the microfluidisation process, two key factors - pressure and number of cycles were screened and 8 cycles at 2000 bar was the most efficient parameter. The nanocrystals made in EPAS process were smaller, more uniform and had a narrower distribution than the microfluidisation nanocrystals. Differential scanning calorimetry (DSC) and X-ray diffraction confirmed the crystalline states that were both reserved. The solubility was greatly improved by the two methods and the EPAS nanocrystals were more soluble due to the smaller size. An enhanced dissolution was obvious in vitro. And the stable nanocrystals were successfully achieved by the two methods.