布南色林自乳化制剂的研究  

Study of the self-emulsifying drug delivery system of blonanserin

作　　者：崔健 刘红兵 张宇[1] CUI Jian;LIU Hongbing;ZHANG Yu(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Beijing Yimin Pharmaceutical Co.,Ltd.,Beijing 101300,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]北京益民药业有限公司,北京顺义101300

出　　处：《沈阳药科大学学报》2020年第7期577-584,610,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的通过处方筛选确定布南色林自乳化制剂的组成,以期提高口服生物利用度。方法通过初步考察布南色林在不同辅料中的溶解度和各辅料混合后形成自乳化制剂的能力,绘制伪三元相图确定辅料。运用星点设计-效应面优化法,通过考察乳化时间、载药量和形成乳液滴的粒径等,对自乳化制剂进行评价,并通过总评"OD"值确定处方组成及辅料用量。通过对SD大鼠灌胃试验考察自乳化制剂对药物动力学的影响。结果布南色林自乳化制剂最终处方组成为油酸乙酯-Tween 80-Transcutol?P(质量比为1.00∶1.95∶0.85),所制备处方可以在1 min内自动形成具有淡蓝色乳光的微乳液,形成的微乳液的平均粒径为44.3 nm,载药量为35.3 g·L-1,Zeta电位为-20.21 mV。布南色林原料药在pH6.8的磷酸盐缓冲溶液中在60 min内的溶出度小于30%,而本文作者所制备的自乳化制剂可在5 min内基本全部溶出。大鼠口服布南色林自乳化制剂后在各时间点的血药浓度高于口服布南色林原料药,口服生物利用度提高7.29倍。结论该方法能成功的将布南色林制成自乳化制剂,并显著提高布南色林的口服生物利用度。Objective To determine the composition of the self-emulsifying drug delivery system of blonanserin by screening different excipients in order to improve the oral bioavailability of blonanserin.Methods The solubility and emulsifying ability of BNS in different excipients were initially investigated,and then the excipients used for SEDDS of BNS were selected based on the maximum of Pseudo-ternary diagram.The self-emulsifying system was optimized by central composite design(CCD)response surface in which the emulsifying time,drug loading and the size of the emulsion droplets were determined.The final composition of the SEDDS of BNS was confirmed by evaluating of the overall desirability(OD).The bioavailability of SEDDS was investigated by gavage in SD rats.Results Ethyl oleate,Tween 80 and Transcutol?P(mass ratio of 1.00∶1.95∶0.85)was used to prepare the optimized preparation,and which could automatically form a microemulsion with light blue opalescence within 1 min.The microemulsion had an average particle size of 44.3 nm.The drug loading was 35.3 g·L-1,and the Zeta potential was-20.21 mV.The dissolution of the raw material of BNS was less than 30%in pH 6.8 PBS within 60 min.In contrast,the dissolution of BNS in SEDDS was almost complete within 5 min.The plasma concentration of BNS in each sampling point following oral administration of the SEDDS was superior to that of BNS raw material,and the oral bioavailability was increased by 7.29 times.Conclusion SEDDS of BNS is successfully prepared in the study,which significantly improves the bioavailability of blonanserin.

关 键 词：布南色林 自乳化制剂 星点设计-效应面优化 生物利用度 

分 类 号：R943[医药卫生—药剂学]