摘要
目的制备并评价马来酸桂哌齐特脂质体(CM-Lip)。方法采用逆向蒸发法制备CM-Lip,以包封率为考察指标,结合鱼骨图分析法和Plackett-Burman(PBD)设计,筛选影响包封率的关键因素;采用Box-Behnken响应面法,对影响CM-Lip包封率的关键因素药物与磷脂比、水合时间、油相(乙醚:乙醇)与水相用量比例进行优化,在二次多项式回归模型的基础上建立CM-Lip制备工艺设计空间,并加以验证,确定CM-Lip最佳处方及制备工艺参数;通过差示热量扫描法(DSC)、红外光谱法验证CM-Lip的形成;采用透射电镜、粒径测定、Zeta电位等对CM-Lip进行表征。结果确定CM-Lip的最佳处方为:药物与磷脂比为1:10,水合时间为1.5 h,油相(乙醚:乙醇)与水相比为3:1;透射电镜证明CM-Lip为球形或椭球形,DSC实验和红外光谱法验证了CM-Lip。CM-Lip的粒径为(114.5±10.3)nm,分散系数(PDI)为0.208,Zeta电位为-17.85 mV,包封率为83.12%,平均载药量为30.17 mg·g^-1。结论CM-Lip制备工艺简单,包封率较高,具有缓释作用,其质量符合2015年版《中华人民共和国药典》要求,为后续新药的开发提供依据。
Objective Preparation and evaluation of cinepazide maleate liposomes(CM-Lip).Methods The CM-Lip was prepared by reverse evaporation method.The encapsulation efficiency was measured.The fishbone diagram analysis method and Plackett-Burman(PBD)design were used to screen the key factors affecting the encapsulation efficiency.The Box-Behnken response surface method was used.The key factors affecting the encapsulation efficiency of CM-Lip were optimized by the ratio of drug to phospholipid,hydration time,oil phase(ether:ethanol)and water phase.Based on the regression model,the design space of CM-Lip preparation process was established and verified to determine the best formulation and process parameters of CM lip;the formation of CM-Lip was verified by differential scanning calorimetry(DSC)and infrared spectroscopy.The CM-Lip was characterized by transmission electron microscopy,particle size measurement and zeta potential.Results The best prescription for determining CM-Lip was as follows:drug to phospholipid ratio was 1:110;hydration time was 1.5 hours;oil phase(ether:ethanol)was 3:1 compared with water.Transmission electron microscopy proves that CM-Lip was spherical or ellipsoid,and DSC test and infrared spectroscopy verified the CM-Lip.The particle size of CM-Lip was(114.5±10.3)nm,and the PDI was 0.208,and the Zeta potential was-17.85 mV.The encapsulation efficiency was 83.12%,and the average drug loading was 30.17 mg·g^-1.Conclusion CM-Lip has a simple preparation process,high encapsulation efficiency,and sustained release effect.Its quality is in line with the requirements of the 2015 edition of the Chinese Pharmacopoeia,which provides a basis for the development of new drugs.
作者
张小雯
孙敬蒙
汪卓明
宁劲涛
王丹
张炜煜
ZHANG Xiaowen;SUN Jingmeng;WANG Zhuoming;NING Jintao;WANG Dan;ZHANG Weiyu(College of Pharmacy,Changchun University of Traditional Chinese Medicine,Changchun 130117,China;Department of Pharmacy,Bethune First Hospital,Jilin University,Changchun 130021,China)
出处
《医药导报》
CAS
北大核心
2021年第2期240-247,共8页
Herald of Medicine
基金
吉林省省级医药健康产业发展专项资金项目(20180311131YY)。
