阿托伐他汀钙自微乳化释药系统的制备与评价  

Preparation and Evaluation of Atorvastatin Calcium Self-microemulsifying Drug Delivery System

作　　者：何瑶[1] 郭晓华[1] 张淼[1] 

机构地区：[1]咸阳职业技术学院医学院,陕西咸阳712000

出　　处：《中国药师》2017年第7期1205-1209,共5页China Pharmacist

摘　　要：目的:开发并优化阿托伐他汀钙自微乳化释药系统,改善阿托伐他汀钙的溶出度。方法:通过溶解度和伪三元相图实验确定油相,表面活性剂和助表面活性剂的种类和用量范围,并通过D-最优混料实验设计优化阿托伐他汀钙自微乳化释药系统的处方,评价了自微乳化释药系统经水稀释后形成微乳的外观,微观形态,粒径分布,Zeta电位;比较市售阿托伐他汀钙片与自制阿托伐他汀钙自微乳化释药系统的体外溶出情况。结果:阿托伐他汀钙自微乳化释药系统的处方组成为:Capmul MCM作为油相,Labrasol作为表面活性剂,Transcutol P作为助表面活性剂,最佳配比为:13.0∶43.5∶43.5。自微乳化释药系统经水稀释后形成的微乳外观呈微泛蓝光的澄清透明状液体;透射电镜下显示其呈圆整,规则球状分布;平均粒径为(34.2±13.6)nm,PdI为(0.169±0.04),Zeta电位为(-21.1±1.3)mV;阿托伐他汀钙自微乳化释药系统在45 min内药物可完全溶出。结论:运用D-最优混料实验设计方法成功开发了阿托伐他汀钙自微乳化释药系统,可以有效提高药物的溶出速度。Objective ： To develop and optimize a self-microemulsifying drug delivery system （SMEDDS） formula for improving the dissolution of atorvastatin calcium. Methods： Solubility and pseudo-ternary phase diagram were used to select the suitable type and a- mount range of oil phase, surfactant and co-surfactant. D-optimal mixture design was used to optimize the formula of atorvastatin calcium SMEDDS. The morphology, particle size distribution and zeta potential of the microemulsion were determined by a dilution method. The in vitro drug release profiles of the marketed atorvastatin calcium tablets and the self-made SMEDDS were compared. Results： The formula of atorvastatin calcium SMEDDS was as follows ： Capmul MCM as the oil phase, Labrasol as the surfactant and Transcutol P as the co-surfactant with the optimal weight ratio of 13.0 ： 43.5 ： 43.5. The self-made SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope. The particle size, PdI and zeta potential of the self-made SMEDDS was （34.2±13.6） nm, （0. 169±0.04） and （ -21.1±1.3） mV, respectively. The in vitro release profile indicated that the accumulated release of the self-made SNEDDS reached up to nearly 100% in 45 min. Conclusion： The optimal formula of atorvastatin calcium SMEDDS optimized by D-optimal mixture design can improve the drug dissolution rate effectively.

关 键 词：阿托伐他汀钙 自微乳化释药系统 D-最优混料实验设计 溶出度 

分 类 号：R944.9[医药卫生—药剂学]