Study On The Silybin Lipid Emulsion

In recent years, as a novel drug delivery system, intravenous lipid emulsion(LE) could improve drug efficacy, reduce side effects, and has sustained releasing and targeting function. The poor water solubility and low-bioavailability of silybin has restricted its clinical applications. In this study, silybin was chosen as a model drug and LE as the carrier for developing the silybin intravenous lipid emulsions(SLE). The silybin phospholipid complex and its intravenous lipid emulsions preparation methods, physical and chemical properties, tissue distribution in mice and pharmacodynamics were studied in the subject.The HPLC methods were established for silybin determination, silybin achieved a good separation without interference, which provided analysis methods for subsequent experiments.The formation mechanism of silybin-phospholipid complex(SPC) and its physicochemical characteristics were studied on the basis of optimizing the preparations by using solvent-evaporation method. The complex rate was achieved no less than 99%. The liposolubility of silybin was increased significantly after forming the phospholipid complex by the apparent partition coefficients study.Then, the effects of the amount of oil phase, emulsifier and additional dosage, lecithin in the oil-water ratio, cutting technology and other factors on the stability and appearance of SLB primary emulsion were evaluated. The high-pressure homogenization machine parameters were studied by the PDI. Combined with orthogonal design, the best SLB emulsion formulation and process was screened out. Preliminary study of the SLE sterilization showed that the temperature should be avoided (> 40℃), and light, low temperature did not affect its stability. The size of SLE was 152.3±4.6nm, Zeta potential was-26.8±2.4mV and the encapsulation efficiency was 89.30%.Lastly,compared with the tissue distribution of silybin injection in mice, the AUC of SLE in liver was 21.54 times of injection. (TE)CSLE of liver was 2.34 times higher than injection, and the SLE RTEC of liver was 242.70. The silybin lipid emulsion changed the drug distribution in mice and showed good liver targeting property.