紫杉醇衍生物(TAH)脂质体的处方工艺优化及初步质量评价研究  

Optimization of the formulation technology and preliminary quality evaluation of paclitaxel derivative(TAH)liposomes

作　　者：张辛宁 刘杨佳 吴悦 叶田田[2] 牟良玉 刘东春[1] 王淑君[2] ZHANG Xinning;LIU Yangjia;WU Yue;YE Tiantian;MU Liangyu;LIU Dongchun;WANG Shujun(School of Chinese Medicine,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学中药学院,辽宁沈阳110016 [2]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国药剂学杂志》2021年第4期110-122,135,共14页Chinese Journal of Pharmaceutics

摘　　要：目的考察紫杉醇衍生物(TAH)脂质体制备方法,优化其处方组成及工艺条件,并进行初步质量评价。方法采用薄膜分散法制备TAH脂质体,采用单因素考察脂质体膜材组成、药脂比、抗氧剂种类及用量、成膜温度、水化温度、转速及时间、均质压力和次数,确定最优处方及工艺,同时对制备的脂质体进行初步质量评价。结果确定最优处方及工艺的质量比为m(药):m(大豆卵磷脂):m(胆固醇)=1:20:2,抗氧剂BHT的质量浓度为1 g·L^(-1),成膜温度:40℃,水化温度:40℃,水化时间:30 min,均质次数:10次,均质压力:800 bar。其平均粒径为78.24 nm,Zeta电位为-0.150 mV,包封率为(92.89±1.32)%,载药量为(4.03±1.00)%,均符合制剂要求。结论最优处方制备的脂质体粒径较小,包封率较高,抗氧剂二丁基羟基甲苯(butylated hydroxytoluene,BHT)的加入提高了制剂稳定性,且不影响含量和有关检测结果,质量可靠,工艺稳定,适用于工业化大生产。Objective To investigate the preparation method of paclitaxel derivative(TAH)liposomes,optimize its prescription composition and process conditions,and conduct preliminary quality evaluation.Methods TAH liposomes were prepared by thin-film dispersion method,and single factor method was used to investigate the composition of liposome membrane material,drug-lipid ratio,types and dosage of antioxidants,film-forming temperature,hydration temperature,rotation speed and time,homogeneous pressure and frequency.The optimal prescription and process were determined,and a preliminary quality evaluation of the prepared liposomes was conducted.Results The optimal prescription and process are determined as follows:m(medicine):m(soy lecithin):m(cholesterol)=1:20:2,antioxidant BHT concentration was 1g/L,film forming temperature was at 40℃;hydration temperature was at 40℃;hydration time was 30 min;homogenization times were 10 times;homogenization pressure was 800 bar.The average particle size was 78.24 nm;the Zeta potential was-0.150 mV;the encapsulation rate was(92.89±1.32)%;and the drug loading efficiency was(4.03±1.00)%,which meet the preparation requirements.Conclusions The liposomes prepared by the best prescription have a small particle size and a high encapsulation rate.The addition of antioxidant butylated hydroxytoluene(BHT)improves the stability of the preparation without affecting the content and related test r esults.The quality is reliable and the process is stable.It is suitable for large-scale industrial production.

关 键 词：紫杉醇衍生物 脂质体 包封率 粒径 

分 类 号：R94[医药卫生—药剂学]