多西他赛白蛋白纳米粒的制备及处方工艺优化  

Preparation and optimization of formulation and manufacturing process for Docetaxel albumin nanoparticles

作　　者：陈东健 肖健阳[2] 罗美岭 田柳 乔明曦 张晓君[3] CHEN Dongjian;XIAO Jianyang;LUO Meiing;TIAN Liu;QIAO Mingxi;ZHANG Xiaojun(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.Ltd.,Shijiazhuang 050011,China;Beijing Kangchuanglian Biopharmaceutical Technology Research Co.Ltd.,Beijing 102600,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]石药集团中奇制药技术(石家庄)有限公司,河北石家庄050011 [3]北京抗创联生物制药技术研究有限公司,北京102600

出　　处：《中国药剂学杂志（网络版）》2024年第2期40-50,共11页Chinese Journal of Pharmaceutics：Online Edition

摘　　要：目的优化多西他赛白蛋白纳米粒(DTX-HSANps)的处方和制备工艺,并对其进行初步的质量评价。方法采用NabTM技术制备DTX-HSANps,通过Plackett-Burman实验设计,对DTX在油相中的浓度、人血白蛋白(Humanserumalbumin,HSA)在水相中的浓度、水相溶液的pH、油水相体积比、乳化器的转速和均质压力共6个因素进行考察,以粒径、稳定性及过药量作为指标,筛选影响产品质量的关键因素。采用Box-Behnken效应面法筛选最优的处方工艺,对样品的粒径、包封率、载药量、微观形态进行表征。结果确定HSA在水相中的浓度、水相溶液的pH和均质压力为影响产品质量的关键因素。根据最佳处方工艺制备三批样品,冻干复溶后,DTX-HSA Nps的粒径为(107.3±1.3)nm,PDI为(0.123±0.012),载药量为(3.9±0.2)%,包封率为(92.0±0.6)%。结论所制备的DTX-HSANps粒径分布均匀,理化性质稳定,具有较高的产品开发价值以及较好的临床应用潜力。Objective To optimize the formulation and process of docetaxel albumin nanoparticles(DTX-HSA Nps),and to conduct preliminary quality evaluation.Methods DTX-HSA Nps were prepared by NabTM technology.Plackett-Burman experiment design was used to investigate the effects of DTX concentration in oil phase,the concentration of human serum albumin in water phase,the pH of aqueous solution,the volume ratio of oil to water phase,the speeds of the emulsifier and the homogenization pressure on particle size,stability and drug content after filtration.The key factors influencing product quality were screened by Plackett-Burman experiment.Box-Behnken design-response surface method was used to screen the optimal formulation process.Finally,the particle size,encapsulation efficiency,drug loading and micromorphology of DTX-HSA Nps were characterized.Results The key factors that affect the quality of the product were HSA concentration in water phase,the pH of the aqueous solution and homogeneous pressure.Three batches of DTX-HSA Nps were prepared according to the optimum formulation and process.After lyophilization and redissolving,the particle size of DTX-HSA Nps was(107.3±1.3)nm,the PDI was(0.123±0.012),the drug loading was(3.9±0.2)%,and the encapsulation efficiency was(92.0±0.6)%.Conclusion The prepared DTX-HSA Nps have uniform particle size distribution and stable physicochemical properties,which have high product development value and good clinical application potential.

关 键 词：药剂学 白蛋白纳米粒 NabTM 多西他赛 PLACKETT-BURMAN Box-Behnken 

分 类 号：R94[医药卫生—药剂学]