硫酸长春新碱热敏脂质体的制备和质量评价  

Preperation and Quality Evaluation of Vincristine Sulfate Thermosensitive Liposomes

作　　者：李明媛[1] 张慧[1] 杨臻博[1] 李晗[1] 梅乐[1] 梅兴国[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药学杂志》2014年第18期1615-1619,共5页Chinese Pharmaceutical Journal

基　　金：重大新药创制--"十二五"综合性新药开发大平台;药物新制剂技术平台(2012ZX09301003-001-009)

摘　　要：目的制备硫酸长春新碱(vincristine,VCR)热敏脂质体,测定其粒径及体外释药热敏特性,建立脂质体含量、包封率及有关物质的测定方法。方法 pH梯度主动载药法制备长春新碱热敏脂质体,激光粒度分析仪测定脂质体粒径;以水为释放介质,分别考察脂质体在37和42℃的释放特性;超滤离心法测定脂质体包封率;HPLC测定脂质体中长春新碱的含量及有关物质。结果长春新碱热敏脂质体的平均粒径为(86±6)nm,37℃几乎不释放,42℃30 min内释放约90%;3批样品包封率均高于95%;含量为1.92 mg·mL-1,有关物质符合药典要求。结论长春新碱长循环热敏脂质体的制备工艺简单稳定,所制备的脂质体粒径均一,具有明显的热敏特性,包封率高,适于-20℃长期储存。脂质体含量、包封率及有关物质测定方法简便、快速、准确。OBJECTIVE To prepare vincristine sulfate （VCR） thermosensitive liposomes, and evaluate its particle size and reease characteristics in vitro and establish the methods for determination of content, entrapment efficiency and related substances. METHODS pH gradient active drug-loading was used to prepare VCR liposomes;photon correlation spectroscopy was used to determine the particle size ; the in vitro release properties of VCR liposomes in 37 and 42℃ water were compared ; the entrapment efficiency of the liposomes was determined by using centrifugal uhrafihration; HPLC was applied for the determination of content and related substances. RESULTS The average particle size of VCR liposomes was （86 ± 6） nm, and the liposomes hardly released at 37 ℃ and released about 90% within 30 min at 42 ℃, showing obvious thermosensitive property; the entrapment efficiencies for 3 batches were higher than 95% ; the content was 1.92 mg · mL^-1, with the related substance in line with the pharmacopoeia requirements. CONCLUSION The preparation process for VCR liposome is simple and stable. The liposomes have narrow particle size distribution as well as obvious thermosensitire property, and it also has high drug encapsulation efficiency and is stable at -20 ℃in long-term storage. The determination methods for the content, encapsulation efficiency and related substances of VCR liposomes are simple, rapid and accurate.

关 键 词：硫酸长春新碱 热敏脂质体 粒径 热敏特性 包封率 超滤离心 含量 有关物质 

分 类 号：R944[医药卫生—药剂学]