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目的:采用星点设计法,以平均粒径、稳定性常数及包封率为考察指标,优化丹参酮ⅡA脂微球处方。方法:以平均粒径、稳定性常数及包封率为评价指标,考察了蛋黄卵磷脂用量(A)、泊洛沙姆用量(B)、大豆油占油相总量的百分比(C)对丹参酮ⅡA脂微球制剂性质的影响。用二项式拟合建立指标与因素之间的数学关系,根据评价指标的最佳数学模型描绘效应面,经效应面法预测最佳处方,并进行预测分析。按照优化的处方制备丹参酮ⅡA脂微球,并对其进行常规的质量评价研究。结果:各指标的二项式方程拟合较好,平均粒径、稳定性常数和包封率的相关系数分别为0.97,0.92,0.84,可信度较高。优化后的处方为:蛋黄卵磷脂1.38 g,F68 0.19 g,LCT 2 g,MCT 18 g,优化处方各指标和目标值接近。按优化处方制备的丹参酮ⅡA脂微球的平均粒径为203 nm,粒径分布为0.1,ζ电位为36,包封率为93%,载药量为0.8 mg·m L-1;室温条件下避光放置7个月,其粒径、ζ电位、载药量、包封率、p H未见明显变化。结论:星点设计-效应面法适用于脂微球乳剂的处方优化,所建立的数学模型预测性良好;优化后的丹参酮ⅡA脂微球符合药剂学要求。
OBJECTIVE: To optimize the formulation of tanshinone ⅡA lipid microspheres by the method of star point design with average particle size, stability constant and entrapment efficiency as indexes. Methods: The average particle size, the stability constant and the entrapment efficiency were used as indexes to evaluate the effects of egg yolk lecithin dosage (A), poloxamer dosage (B), soybean oil percentage of total oil phase (C) Influence of Tanshinone ⅡA Liposome Preparation Properties. The binomial fitting is used to establish the mathematical relationship between the index and the factor. The effect surface is drawn according to the best mathematical model of the evaluation index, the best prescription is predicted by the effect surface method, and the prediction is analyzed. Tanshinone Ⅱ A lipid microspheres were prepared according to the optimized prescription and routine quality evaluation was conducted. Results: The binomial equation of each index fits well, and the correlation coefficient of average particle size, stability constant and entrapment efficiency are 0.97, 0.92 and 0.84, respectively, with high credibility. Optimized prescription: egg yolk lecithin 1.38 g, F68 0.19 g, LCT 2 g, MCT 18 g, the optimal formulation of the indicators and the target value close. The average particle size of tanshinone ⅡA lipid microspheres was 203 nm, the particle size distribution was 0.1, the zeta potential was 36, the entrapment efficiency was 93% and the drug loading was 0.8 mg · m L-1. The room temperature Under the dark place for 7 months, its particle size, zeta potential, drug loading, encapsulation efficiency, p H no significant change. Conclusion: The star-point design-response surface method is suitable for the formulation optimization of lipid microsphere emulsions. The mathematical model established has good predictability. The optimized tanshinone Ⅱ A lipid microspheres meet the requirements of pharmacy.