目的 优化和厚朴酚自微乳给药系统（HN-SMEDDS）制备工艺，并对其质量进行评价。方法 采用拟三元相图法筛选HN-SMEDDS的辅料。在此基础上，以微乳粒径大小为评价指标，应用星点设计-响应面法优化HN-SMEDDS处方。然后采用电导率法对最优处方的HN-SMEDDS进行结构表征，并对其质量进行体外评价。结果 优化后HN-SMEDDS配方为聚山梨酯80 71.54%，PEG200 14.62%，花生油10.56%，蓖麻油3.28%；在该配方下，和厚朴酚载药质量浓度为60 mg/mL，用纯水将其稀释3倍以上可形成水包油（O/W）微乳液，其平均粒径为（16.83±0.35）nm，多分散系数（PDI）为0.189±0.021，Zeta电位为（−15.530±0.205）mV。HN-SMEDDS在5~400倍稀释形成的微乳液稳定性良好，分散介质类型对其粒径无显著性影响，在−20℃或在室温条件下贮存15 d仍可稀释形成稳定微乳液。该自微乳可显著延长和厚朴酚在人工胃液中的释放时间和提高其在人工小肠液中的释放度。结论 优化的HN-SMEDDS制备工艺简单、微乳粒径小、PDI小、稳定性好、制备成本低、能有效提高和厚朴酚在水中的溶解度和在人工小肠液中的释放度。

Objective To prepare and optimize honokiol self-microemulsion drug delivery system (HN-SMEDDS) and evaluate its quality. Methods Pseudo-ternary phase diagrams were applied to screen the excipients of HN-SMEDDS. And then, using the particle size of microemulsion as the evaluation index, the formulation of HN-SMEDDS was optimized by central design-response surface methodology. The structure of the HN-SMEDDS prepared under the optimized formulation was characterized by the electrical conductivity method, and the quality of HN-SMEDDS were evaluated in vitro. Results The optimum formulation of HN-SMEDDS was as following:Polysorbate-80 71.54%, PEG200 14.62%, peanut oil 10.56%, castor oil 3.28%. The drug loading capacity of this HN-SMEDDS was 60 mg/mL. HN-SMEDDS could be transformed into O/W microemulsions after being diluted above three-fold using deionized water. The average particle size, PDI and Zeta potential of the microemulsion were (16.83 ±0.35) nm, 0.189 ±0.021, and (−15.530 ±0.205) mV. HN-SMEDDS had good stability between 5 and 400 times dilutions, and the types of dispersion media used for HN-SMEDDS dilution had no significant effect on the particle size of the microemulsion. And HN-SMEDDS was able to form a stable self-microemulsion after being stored for 15 d at −20℃ or room temperature. HN-SMEDDS prolonged the release time of honokiol in artificial gastric fluid and improved its release in artificial intestinal fluid. Conclusion The optimized HN-SMEDDS possesses have the advantages of easy preparation process, small particle size and good stability with low cost and can effectively improve the solubility of honokiol in water and the release of honokiol in artificial intestinal fluid.

R283.6

国家重点研发计划资助（2019YFD0900105）；国家自然科学基金项目（31960739）；海南临高县海洋与渔业局小瓜虫病防控技术研究服务项目（ZLHX2018-124R）