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目的:优化银杏内酯B(GB)自微乳药物传递系统(SMEDDS)的处方,并初步评价其质量和安全性。方法:以微乳粒径、Zeta电位、药物平衡溶解度为指标,油相质量分数、混合表面活性剂比例、表面活性剂和助表面活性剂的比例为考察因素,采用伪三元相图结合星点设计-效应面法优选GB-SMEDDS的处方工艺。采用HPLC测定GB含量,并对自微乳的pH、形态学、粒径分布、Zeta电位、稳定性及部分安全性等进行评价。结果:最优处方为辛酸/癸酸三甘油脂、聚氧乙烯35蓖麻油、卵磷脂、乙醇质量比25.99∶39.47∶9.87∶24.67,载药量(24±1.4)g.L-1,粒径30～60 nm,GB-SMEDDS于1周内在常温、高温及低温状态下稳定性良好,通过溶血试验、血管刺激、急性毒性评价给药安全性良好。结论:星点设计-效应面法适用于GB-SMEDDS的处方优化,所建模型预测性良好,且GB自微乳制备工艺简单、性质稳定、质量易控。
OBJECTIVE: To optimize the prescription of Ginkgolide B (GB) self-microemulsion drug delivery system (SMEDDS) and evaluate its quality and safety. Methods: Taking the microemulsion diameter, Zeta potential and drug balance solubility as indexes, the mass fraction of oil phase, the ratio of mixed surfactant, the ratio of surfactant and cosurfactant were investigated. The pseudo-ternary phase diagram Point Design - Response Surface Methodology GB-SMEDDS preferential treatment process. The content of GB was determined by HPLC, and the pH, morphology, particle size distribution, Zeta potential, stability and partial safety of self-microemulsion were evaluated. Results: The optimal prescription was caprylic / capric triglyceride, polyoxyethylene 35 castor oil, lecithin and ethanol mass ratio of 25.99:39.47:9.87:24.67, drug loading (24 ± 1.4) gL-1, particle size of 30 ~ 60 nm. GB-SMEDDS has good stability at room temperature, high temperature and low temperature in 1 week. It has good safety through hemolysis test, blood vessel stimulation and acute toxicity evaluation. Conclusion: The star-point design-response surface method is suitable for the formulation optimization of GB-SMEDDS. The predictive model is good, and the GB self-microemulsion preparation technology is simple, stable in nature and easy to control in quality.