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为提高水飞蓟宾的口服生物利用度,以水飞蓟宾纳米晶为固体微粒,采用高压匀质法制备水飞蓟宾纳米晶自稳定Pickering乳液(silybin nanocrystalline self-stabilizing Pickering emulsion,SN-SSPE)。考察匀质压力、药物加入量对SN-SSPE形成的影响,以激光共聚焦显微镜、扫描电镜和原子力显微镜等研究表征SN-SSPE的乳滴粒径与形态结构。从乳液的稳定性、体外药物释放和体内药物吸收等方面对SN-SSPE进行评价。结果发现,匀质压力越大,纳米晶粒径越小,压力大于100 MPa时粒径变化较小;水飞蓟宾加入量达到300 mg及其以上时,纳米晶能够完全覆盖油滴表面,形成稳定的SN-SSPE。优化的SN-SSPE乳滴粒径为27.3±3.1μm,具有明显的核壳状结构。SN-SSPE的稳定性比SN纳米晶混悬液高,至少可稳定40天以上。SN-SSPE的体外释放速率与纳米晶混悬液相似,比原料药显著加快。大鼠灌胃后,SN-SSPE的血药峰浓度相对于纳米晶混悬液和原料药分别提高了2.5倍和2.3倍,AUC分别提高了1.4倍和3.8倍。研究结果表明,难溶性药物纳米晶可以稳定Pickering乳液;药物纳米晶自稳定Pickering乳液对于提高难溶性药物的口服生物利用度有着广阔的应用前景。
In order to improve the oral bioavailability of silibinin, silybin nanocrystalline self-stabilizing Pickering emulsion (SN-CSF) was prepared by high pressure homogenization using silybin nanocrystals as solid particles. SSPE). The effect of homogenization pressure and drug loading on the formation of SN-SSPE was investigated. The particle size and morphology of SN-SSPE were characterized by laser confocal microscopy, scanning electron microscopy and atomic force microscopy. SN-SSPE was evaluated from the aspects of emulsion stability, in vitro drug release and in vivo drug absorption. The results show that the bigger the homogenization pressure is, the smaller the nanocrystalline grain size is and the smaller the change of particle size is when the pressure is more than 100 MPa. When the content of silybin reaches 300 mg and above, Form a stable SN-SSPE. Optimized SN-SSPE emulsion droplets size of 27.3 ± 3.1μm, with a clear core-shell structure. The stability of SN-SSPE is higher than that of SN nanocrystal suspension, which can be stable for at least 40 days. The release rate of SN-SSPE in vitro is similar to that of nanocrystalline suspension, which is significantly faster than that of bulk drug. After gavage, the peak plasma concentration of SN-SSPE was increased 2.5-fold and 2.3-fold, respectively, relative to that of nanocrystal suspension and drug substance. The AUC was increased by 1.4-fold and 3.8-fold, respectively. The results show that the insoluble drug nanocrystal can stabilize Pickering emulsion. The drug nanocrystal self-stabilized Pickering emulsion has broad application prospects for improving the oral bioavailability of the insoluble drug.