尼莫地平自微乳化释药系统的研制

Study on Nimodipine Self-microemulsifying Drug Delivery System

目的:研制尼莫地平(nimodipine,NM)自微乳化释药系统(SMEDDS)。方法:以溶解度,相容性试验、自乳化效率及伪三元相图法筛选最佳油相、表面活性剂及助表面活性剂;以星点设计-效应面法优化处方;对NM-SMEDDS分散后粒径、体外溶出度及初步稳定性进行考察。结果:经处方筛选和星点效应面法优化得出最佳处方为:Captex200P,Cremophor EL,Labrosol分别为油相,乳化剂和助乳化剂,比例为30∶47∶23;NM-SMEDDS的粒径分别为33.8±3.42 nm,1 h累积溶出百分率为98.83%,约为市售片剂的3.84倍;经高温(60℃)、低温(4℃)、强光(4 500±500)Lx考察10 d,除强光可引起NM含量降低外,其他各项指标均无明显变化。结论:该处方及工艺筛选、优化法简便可行,容易控制,制备得到的NM-SMEDDS体外溶出度显著增加,稳定性较好,为进一步研发尼莫地平新制剂提供了理论和试验基础。

Objective： To prepare nimodipine self-microemulsifying drug delivery system （NM-SMEDDS）. Method： The optimal oil phase, surfactant and cosurfactant of NM-SMEDDS were screened using solubility, compatibility, self-microemulsifying efficiency and pseudo-ternary phase diagram as the evaluation indices and method. The formula was optimized by central composite design-re- sponse surface methodology. The microemulsion particle size after dispersion, dissolution and preliminary stability of NM-SMEDDS were determined. Result： The optimal formula consisted of Captex200P, Cremophor EL and Labrasol as the oil phase, surfactant and cosurfactant, respectively with the ratio of 30： 47： 23. The particle diameter of NM-SMEDDS was（33.8 ± 3.42） nm. The accumulative dissolution of NM-SMEDDS was 98.83% , which was about 3.84 times as much as that of the marketed tablets. There was no obvious change under the conditions of high temperature （60℃）, low temperature （4℃） and strong light （4 500 ± 500 Lx） in 10 days except the content decrease in strong light. Conclusion： The optimal preparation method is simple, feasible and easy to control. The dissolu-tion of NM is significantly imoroved by NM-SMEDDS with better stability. It can orovide the foundation for the new dosaze form of NM.