水飞蓟宾纳米晶自稳定Pickering乳液的制备及评价  

Preparation and evaluation of silybin nanocrystallines self-stabilizing Pickering emulsion

作　　者：张继芬[1] 刘川 张焦[1] 易涛[3] 

机构地区：[1]西南大学药学院,重庆400716 [2]广安市食品药品检验检测中心,四川广安638500 [3]澳门理工学院高等卫生学校,澳门00853

出　　处：《药学学报》2016年第5期813-820,共8页Acta Pharmaceutica Sinica

基　　金：西南大学基本科研业务费专项资金项目(XDJK2014C089);澳门理工学院资助研究项目(RP/ESS-06/2014)

摘　　要：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。A new silybin nanocrystallines self-stabilizing Pickering emulsion（SN-SSPE） was developed using the high pressure homogenization method to improve the oral bioavailability of silybin.The influences of homogenization pressure from 50 to 120 MPa and drug content from 100 mg to 1000 mg on the formation of SN-SSPE were studied.The morphology,structure and size of emulsion droplet in SN-SSPE were characterized using scanning electron micrograph and confocal laser scanning microscope.SN-SSPE was evaluated,including stability,in vitro release and in vivo oral bioavailability.The particle size of silybin nanocrystallines（SN-NC） was decreased as the pressure increased until 100 MPa.When the drug content reached 300 mg or above,stable SN-SSPE was formed from sufficient SN-NC covering surfaces of oil droplets completely.The emulsion droplet of SN-SSPE with the size of 27.3 ± 3.1 μm showed a core-shell structure consisting of oil droplet as core and SN-NC as shell.SN-SSPE showed a high stability over 40 days.In vitro release rate of SN-SSPE was faster than silybin coarse powder and similar to silybin nanocrystallines suspension（SN-NCS）.After intragastric administration in rats,the peak concentration of SN-SSPE was increased by 2.5-fold and 2.3-fold compared with SN-NCS and silybin coarse powder,respectively.The AUC of SN-SSPE was increased by 1.4-fold and 3.8-fold compared with SN-NCS and silybin coarse powder,respectively.All these results showed that nanocrystallines of the poorly soluble drug could stabilize Pickering emulsions,which provides a promising application to the improvement of the oral bioavailability of poorly soluble drugs.

关 键 词：Pickering乳液 水飞蓟宾 纳米晶 

分 类 号：R943[医药卫生—药剂学]