目的 制备去氢骆驼蓬碱包合物脂质体（harmine drug-in-cyclodextrin-in-liposome，Har-DCL），并评价该制剂的理化性质和体外特性。方法 以包合物溶解度、包合率、体外释放考察为指标考察去氢骆驼蓬碱包合物（harmine inclusion complex，Har-CD）的最佳工艺。采用傅里叶红外光谱仪、扫描电子显微镜、X射线衍射分析等确定Har-CD的包合程度，以证实制备方法的可行性。采用pH梯度主动载药法考察磷脂与胆固醇质量比，Har与脂质体质量比对Har-DCL粒径分布、载药量及包封率的影响，以得到粒径分布均匀，载药量高且稳定的Har-DCL。结果 饱和水溶液法制备的包合物溶解度为42.81μg/mL，包合率为95.50%，为最佳制备方法。羟丙基-β-环糊精与Har的质量比为8∶1时，制成的包合物溶解度最好，载药量为（107.0±0.4）mg/g，包合率为（96.33±0.39）%。使用pH梯度法以磷脂与胆固醇质量比为3∶1，药脂比为1∶10制备的脂质体平均粒径为（85.24±0.60）nm，ζ电位为（-3.57±0.28）mV，载药量和包封率分别达到（1.740±0.001）mg/mL和（95.650±0.003）%。加入20.0mg/mL乳糖得到的脂质体冻干粉外观饱满，复溶性能良好。结论 使用饱和水溶液法让Har进入环糊精的空腔结构，可以有效增强Har水溶性。Har以Har-CD的形式从脂质体双分子层之间，转移至内水相而得到的Har-DCL均匀稳定，对Har新剂型的开发提供参考。

Objective To prepare harmine drug-in-cyclodextrin-in-liposome (Har-DCL) and evaluate the physicochemical properties and in vitro characteristics of this formulation. Methods The solubility, inclusion rate and in vitro release of the inclusion complex were used as the evaluation to obtain optimal formulation of harmine inclusion complex (Har-CD). The degree of inclusion of Har-CD was determined using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction analysis, etc. to confirm the feasibility of the preparation method. The pH gradient active drug loading method was used to investigate the mass ratio of phospholipid and cholesterol, and the effect of the mass ratio of liposome and Har on the particle size distribution, drug loading and encapsulation efficiency of Har-DCL. Influence of drug dosage and to obtain Har-DCL with uniform particle size distribution, high drug loading and stable Har-DCL. Results The optimum preparation method was confirmed for Har-CD preparation: the solubility of the inclusion compound prepared by the saturated aqueous solution method was 42.81 μg/mL, and the inclusion rate was 95.50%. The inclusion compound with the mass ratio of hydroxypropyl-β-cyclodextrin and Har of 8:1 had the best solubility, the drug loading capacity and the inclusion rate of Har-CD was (107.0 ±0.4) mg/g and (96.33 ±0.39)%, respectively. The mean particle size of liposomes prepared with phospholipid: cholesterol ratio of 3:1 and drug-lipid ratio of 1:10 using the pH gradient method was (85.24 ±0.60) nm, and the ζ potential was (-3.57 ±0.28) mV. The drug loading capacity and encapsulation efficiency reached (1.740 ±0.001) mg/mL and (95.650 ±0.003)%, respectively. The liposome freeze-dried powder obtained by adding 20.0 mg/mL lactose had a plump appearance and good reconstitution performance. Conclusion The use of saturated aqueous solution method to make Har into the cavity structure of cyclodextrin can effectively enhance the water solubility of Har. The Har-DCL obtained by transferring Har in the form of Har-CD from the liposome bilayer to the inner aqueous phase is uniform and stable, which provides a reference for the development of new formulation for Har.

R283.6

江西省自然科学基金资助项目(20202BAB216038);江西中医药大学博士启动基金(2018WBZR001);国家自然科学基金地区项目(82260816);江西中医药大学中药制剂技术与制药装备创新团队(CXTD22006);江西中医药大学大学生创新创业训练计划项目(202210412363)