目的 制备粒径均一、复水性良好的甘草次酸拼合物TOGA-X4微粒，得到稳定可靠的制剂工艺，评价其体外释药特性。方法 以平均粒径、多分散指数和复水性为指标，通过单因素分析法对不锈钢膜乳化法制备抗肿瘤活性物质TOGA-X4微粒的工艺进行考察及优化，同时通过扫描电子显微镜观察微粒外观形态；采用直接释药法测定TOGA-X4微粒和原粉的累积释放率，并采用不同释放模型拟合体外释药曲线，对比评价其体外释药特性。结果 优选的最佳制剂工艺为油相含TOGA-X4质量浓度5 mg/mL，水相PVA质量浓度30 mg/mL，油水比1：1，过膜压力0.4 MPa，冻干保护剂为质量浓度50 mg/mL蔗糖水溶液，固化温度为70℃。TOGA-X4微粒中TOGA-X4的释放曲线符合Logistic动力学方程，TOGA-X4原粉的释放曲线符合零级动力学方程。结论 不锈钢膜乳化法制备微粒工艺简单、稳定、可靠，提高了难溶性药物的溶出速率，在难溶性药物微粒的制备中具有优越性。

Objective To prepare TOGA-X4 microparticles with uniform size and good rehydration property and to obtain the stable and reliable preparation process, and evaluate the in vitro release characteristics. Methods With the average particle size, polydispersity index and rehydration as indexes, optimizing the process of antitumor active substance TOGA-X4 microparticles by stainless steel rapid film emulsification method through single factor investigation to investigate the factors influencing the size and dispersion of the drug microparticles and observe the morphology of the particles by scanning electron microscopy. With the cumulative release degree of TOGA-X4 as index, direct drug release method was adopted to determine the cumulative release rate of TOGA-X4 and the size of TOGA-X4 microparticles. The curve of in vitro drug release was fitted with different release model to estimate the in vitro release characteristics of TOGA-X4 raw powders and TOGA-X4 microparticles. Results The optimized preparation technology contained TOGA-X4 mass concentration of 5 mg/mL in oil phase, PVA mass concentration of 30 mg/mL in for aqueous phase, the ratio of oil to water was 1:1, transmembrane pressure at 0.4 MPa, sucrose aqueous solution of 50 mg/mL as freeze-drying protective agent, curing temperature at 70℃; Compared with other in vitro release models, the logistic equation was the fittest model to TOGA-X4 microparticles, zero order equation was the fittest model to TOGA-X4. Conclusion The preparation of microparticles by stainless steel rapid film emulsification is simple, stable and reliable, which can improve the dissolution rate of insoluble drugs and has advantages in the preparation of microparticles of poorly water-soluble drugs.

国家自然科学基金面上项目（81173562）