羟基喜树碱自乳化传递系统的处方筛选和体外评价

Design and in vitro evaluation of self-emulsifying drug delivery system for HCPT

筛选和制备羟基喜树碱自乳化传递系统的处方并进行体外评价.以平衡质量浓度方法考察了羟基喜树碱在不同的油相、乳化剂和助乳化剂中的质量浓度,通过三元相图辅助筛选处方的组成,采用星点设计-效应面法优化处方中各组分的比例,筛选和制备了羟基喜树碱自乳化传递系统.考察自乳化制剂的粒径、累积溶出度、自乳化速率、微乳形态及其初步稳定性等.筛选出由m(氢化玉米油)∶m(辛酸癸酸甘油酯)=1∶1为混合油相,m(聚氧乙烯蓖麻油)∶m(辛酸葵酸聚乙二醇甘油酯)=2∶1为混合乳化剂,二乙烯基乙二醇单乙醚为助乳化剂和羟基喜树碱组成的自乳化传递系统.所得的优化处方可自发形成均匀球状液滴,微乳平均粒径在30nm左右且分布窄,自乳化速率在5min以内,溶出度在60min内达到90%以上,而且制剂稳定性良好.通过处方研究确定了最优处方,研制了羟基喜树碱自乳化传递系统.

The self-emulsifying drug delivery system （SEDDS） of HCPT was developed and the properties in vitro were assessed. The solubility of HCPT in several oils and emulsifiers and assistant emulsifiers was determined by balance solubility method. Ternary phase diagram was used to select formulation composition and a central composite design-response surface methodology was used to optimize formulation. The droplet size, accumulative dissolving, self- emulsifying rate, microemulsion form and preliminary stability of the preparation were determined to prove that the dosage form is a useful deliverlity system for HCPT. In the optmiaed HCPT-SEDDS, the mixture of m （Maisine 35-1） ： m （GTCC） = 1 ＂ 1, m （CremophorEL）：m （Labrasol）= 2 ： 1, Transcutol P used as oil, emulsifier and assistant emulsifier respectively. This HCPT-SEDDS could be self-emulsified to form uniform globular droplets, the average particle size of microemulsion was about 30 nm and had narrow distribution, the selfemulsifying rate was about 5 min, the accumulative dissolving could reach more than 90% in 1 h, and its stability is fine. The optimized SEDDS for HCPT was obtained.