Optimization and bioavailability evaluation of self-microemulsifying drug delivery system of the daidzein–nicotinamide complex

Abstract

Daidzein (DDZ) is effective in the treatment of a variety of cardiovascular diseases, hypertension and atherosclerosis. However, its extremely low oral bioavailability that is mainly caused by the poor solubility either in the aqueous or oil phase restricts its oral applications. To improve the solubility, a daidzein–nicotinamide (DDZ–NCT) complex was prepared by a solvent evaporation method with DDZ and nicotinamide (NCT). Then self-microemulsifying drug delivery system (SMEDDS) formulation of the DDZ–NCT complex was optimized using central composite design-response surface methodology. The results of powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and Simultaneous DSC-TGA (SDT) indicated that we successfully prepared the DDZ–NCT complex. The saturated solubility of the DDZ–NCT complex was improved 3.49-fold compared to that of DDZ in distilled water. The optimized SMEDDS (DDZ–NCT complex) formulation consisted of 15% Castol oil, 60.7% Cremophor RH40, 24.3% PEG400 and 5% DDZ–NCT complex. The in vitro intestinal absorption in 2 h and the oral bioavailability of SMEDDS (DDZ–NCT complex) were 4.41-fold and 5.69-fold higher than that of pure DDZ, respectively. The data showed that SMEDDS (DDZ–NCT complex) significantly enhanced the solubility and bioavailability of DDZ. Therefore, SMEDDS (DDZ–NCT complex) might be a promising system for the oral administration of DDZ and would be a potential system to deliver poorly water-soluble drugs.