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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 atorvastatin calcium self-microemulsifying drug delivery system to improve the dissolution of atorvastatin calcium. Methods: The types and dosage ranges of oily phase, surfactant and cosurfactant were determined by the experiment of solubility and pseudo-ternary phase diagram. The optimal self-microemulsifying drug release of atorvastatin was optimized by D-optimal mixing experiment System, we evaluated the appearance, microstructure, particle size distribution and Zeta potential of the microemulsion formed after diluted with water. The comparison of the available atorvastatin calcium tablets and the self-made atorvastatin calcium Emulsion release system in vitro dissolution. RESULTS: The formulation of atorvastatin calcium self-microemulsifying drug delivery system consisted of Capmul MCM as the oil phase, Labrasol as the surfactant and Transcutol P as the co-surfactant with the optimal ratio of 13.0:43.5:43.5. Microemulsified drug release system formed after dilution by water appearance of micro-pan-blue light clear transparent liquid; transmission electron microscopy showed a round, regular spherical distribution; average particle size (34.2 ± 13.6) nm, PdI (0.169 ± 0.04), and Zeta potential was (-21.1 ± 1.3) mV. Atorvastatin calcium self-microemulsifying drug delivery system completely dissolved within 45 min. CONCLUSION: Atomvastatin calcium self-microemulsifying drug delivery system was successfully developed by D-optimal mixing experimental design, which can effectively improve the dissolution rate of drug.