Studies On The Intestinal Absorption And Self-Microemulsifying Drug Delivery System Of Daidzein

Self-microemulsifying drug delivery system （SMEDDS） of daidzein was developed on the basis of the studies on the intestinal absorption of daidzein and the factors that affect the absorption of daidzein after oral administration. The resultant SMEDDS helps to improve the oral bioavailability of daidzein. The main studies were as follows.The HPLC analysis of daidzein in vitro was set up and evaluated. A reversed-phase C₁₈ column was used with the mobile phase of methanol-water （55:45, v/v）. The detection wavelength was set at 260 nm. The calibration curve was linear in the range of 0.1-10μg/mL （r=0.9998）. The method was simple, accurate, precise and suitable for the determination of daidzein in the intestinal absorption, solubility, dissolution and stability test.We investigate the absorption characteristics of daidzein across the intestinal membranes by diffusion chamber method. The absorption of daidzin was pH dependent and the absorption was enhanced at weakly alkaline pH. No concentration saturation was observed for the absorption of daidzein, the absorption of daidzein was passive diffusion. The absorption of daidzein has no significantly difference in the presence of verapamil, a typical P-gp inhibitor. Borneol /menthol eutectic mixture was found to enhance the intestinal absorption of daidzein. In the study of formulations, the equilibrium solubility of daidzein in different oils, surfactants and cosurfactants was investigated; pseudo-ternary phase diagrams and self-microemulsification efficiency were assessed. By comparing the size of phase diagrams, the particle size/distribution of resultant microemulsions and the efficiency of self-microemulsification processes, an optimized formulation consisting of Daidzein （3%）, Ethyl oleate （10%）, Cremophor RH40 （58%） and PEG400 （29%） was selected.Basis on the appearance, the Particle size/distribution and microphotograph after self-microemulsification, we evaluated the quality of SMEDDS. In the light test, temperature cycling test and accelerated test, the appearance, content of daidzein and mean particle size of daidzein SMEDDS were studied and the results proved that daidzein SMEDDS was very stable thermodynamically. The release of daidzein from SMEDDS was significantly higher than that of the conventional tablet in simulated gastric and intestinal fluid. The intestinal absorptive of daidzein was significantly increased by SMEDDS.The HPLC analysis of daidzein in rat plasma was set up and evaluated. Daidzein was extracted by protein precipitation; the extracts were injected into a reversed-phase C₁₈ column with the mobile phase of methanol-water （50:50, v/v）. The wavelength was set at 260nm. The blank plasma did not interfere with the determination of daidzein. A good linear relationship for daidzein was found in the range of 15-600ng/mL. The method is simple, accurate and precise for the assay of daidzein in rat plasma. The pharmacokinetics of daidzein SMEDDS and daidzein suspension as a control group in rats was investigated. A series of pharmacokinetic parameters were got, we evaluated these parameters by t-test, finding the distinct difference about C_max and AUC between the SMEDDS and the control group; the relative bioavailability was 250.49%. It can evidently indicate that SMEDDS indeed improves the bioavailability of daidzein.