星点设计效应面法优化非洛地平自微乳给药系统

Optimization of Felodipine Self-microemulsifying Drug Delivery System by Central Composite Design-response Surface Methodology

目的设计非洛地平自微乳给药系统,并进行体外评价。方法测定非洛地平的溶解度,考察油相与乳化剂的相容性,绘制伪三元相图,初步设计自微乳处方;运用星点设计效应面法优化自微乳处方;评价自乳化性能和体外溶出行为。结果非洛地平自微乳处方:油相LABRAFIL M 1944CS为4.4 g,乳化剂Cremophor EL35为5.5 g,助乳化剂PEG400为1.1 g,非洛地平1.0 g;自乳化效率高,乳液澄明稳定,平均粒径为30.4 nm,PDI为0.16;水中溶出很快,5 min内平均溶出度>85%,30 min达99%,24 h后乳滴依然稳定。结论星点设计-效应面法优化的非洛地平自微乳,自乳化性能高,乳液稳定,显著提高非洛地平的体外溶出度。

OBJECTIVE To optimize and assess the formulation of self-microemulsifying drug delivery system mixture for felodipine.METHODS By the means of solubility,compatibility,ternary phase diagram and central composite design-response surface methodology,the preliminary formulation was settled.The self-microemulsifying efficiency,stability and dissolution were studied.RESULTS The optimized formulation was composed of LABRAFIL M 1944CS 4.4 g,Cremophor EL35 as a emulsifier 5.5 g,PEG4001.1 g,and felodipine 1.0 g.The average particle size after the emulsification was 30.4 nm,and PDI was 0.16.The self-emulsifying efficiency and stability was excellent,and accumulative dissolution reached 85%in 5 min,and 99%in 30 min.After 24 h,the felodipine self-microemulsifying particles was still stable.CONCLUSION By the means of central composite design-response surface methodology,a felodipine self-microemulsifying mixture was obtained,which showed a high self-emusifying efficiency,stability and a good in vitro dissolution performance.