雷帕霉素自乳化缓释微丸的研究

Study on Rapamycin Self-emulsifying Sustained Release Pellets

以溶解度结合伪三元相图法,筛选与优化雷帕霉素液体自乳化处方。以羟丙甲基纤维素钠为主要骨架型缓释材料,采用挤出滚圆法制备一种新型的固体自乳化给药系统——雷帕霉素自乳化缓释微丸,并对其重分散性和体外释药进行了研究。结果表明:液体自乳化给药系统的处方是:Capmul MCM(油相)∶辛酸癸酸聚乙二醇甘油酯(表面活性剂)∶聚氧乙烯醚-35蓖麻油(表面活性剂)∶二乙醇单乙基醚(助表面活性剂)=30∶28∶28∶14。制备成的缓释微丸的目标收率为(92.8±2.51)%,遇到重分散后的粒径是35.5±0.5 nm,在体外释药中表明微丸具有良好的缓释性能。以上表明:采用该方法为雷帕霉素的临床应用提供一种良好的应用方法。

The rapamycin liquid self-emulsifying drug delivery system was screened out and optimized by solubility test and pseudo-ternary phase diagram. Sodium hydroxypropyl methylcellulose was used as the main framework for sustained release material. A novel solid self-emulsifying drug delivery system,rapamycin self-emulsifying sustained release pellet was prepared by extrusion-spheronization method, its dispersibility and release in vitro were also studied. The result indicated that, the liquid formulation of self-emulsifying drug delivery system was as follows： Capmul MCM（oil phase）： labrasol（surfactant）： castor oil polyoxyethylene ether-35（surfactant）： diethylene monoethyl ether（cosurfactant） = 30：28：28：14. The target yield of prepared sustained-release pellet was（92.8±2.51）%, and the particle size after re-dispersion was（35.5±0.5）nm. The release test of pellet in vitro showed that the pellet had good sustained-release properties. The results above indicated that this method can provide a good way for clinical application of rapamycin.