吉非替尼脂质体的处方工艺优化  

Optimization of the formulation and process of gefitinib liposomes

作　　者：王宇[1] 何琳[2] 李哲[2] 邓意辉[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]中国医科大学附属第四医院药学部,辽宁沈阳110032

出　　处：《沈阳药科大学学报》2013年第7期495-500,527,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的优化吉非替尼脂质体(gefitinib liposome,GFB-L)的处方组成及工艺条件。方法采用逆相蒸发、改良乙醇注入、薄膜分散3种被动载药法和6种不同梯度的主动载药法制备GFB-L,分别以阳离子交换树脂分离-紫外分光光度法和激光粒度仪测定GFB-L的包封率和粒径,采用单因素考察脂质体膜材组成对包封率及粒径的影响,并进一步通过正交设计法优化GFB-L的处方工艺。结果确定最优处方工艺为∶m(氢化大豆卵磷脂):m(胆固醇)∶m[聚乙二醇单甲醚(2000)-胆固醇琥珀酸酯]=3∶1∶1,m(药)∶m(脂)=1∶8,水化介质:150 mmol.L-1硫酸铵溶液,除盐时间:10 min,载药温度:50℃,载药时间:10 min。结论通过处方工艺优化,GFB-L的平均包封率达97.38%,平均粒径为132.2 nm。Objective To optimize the formulation and process of gefitinib liposomes.Methods Gefitinib liposomes were prepared with three passive loading methods including reverse-phase evaporation,improved ethanol injection,thin-film dispersion and six active loading methods of different gradients.Cation exchange resin separation-ultraviolet spectrophotometry and laser particle analyzer were applied to determine the entrapment efficiency and the size of gefitinib liposomes separately.Single factor experiment was applied to investigate the effect of the composition of liposome membrane on the entrapment efficiency and the size of gefitinib liposomes,and further the orthogonal design was employed to optimize its formulation and process.Results Optimized formulations and processing parameters were as follows：the mass ratio of HSPC：CH：mPEG2000-CHEMS was 3∶ 1∶ 1,drug：lipid was 1∶ 8,150 mmol · L-1 ammonium sulfate solution was chosen as hydration medium,the desalination time was 10 min,the incubation was at 50 ℃ for 10 min.Conclusions Through optimizing the formulations and preparation conditions,gefitinib liposomes are with high entrapment efficiency to 97.38% and the mean diameter to 132.2 nm.

关 键 词：吉非替尼 硫酸铵梯度法 脂质体 正交设计 包封率 粒径 

分 类 号：R94[医药卫生—药剂学]