目的 制备鞣花酸自胶束化固体分散体（ellagic acid-loaded self-micelle solid dispersion，EA-SMSD），考察体外释药情况及口服药动学行为。方法 以EA-SMSD自组装形成胶束的包封率、载药量和沉降率为指标，Box-Behnken设计-效应面法优化EA-SMSD处方工艺。透射电子显微镜（TEM）观察自组装胶束的微观形貌，X射线粉末衍射法（XRPD）分析鞣花酸在EA-SMSD粉末中的晶型，透析袋法考察EA-SMSD在水及模拟胃、肠液中释药情况。以鞣花酸原料药为参考，比较EA-SMSD口服药动学行为。结果 EA-SMSD最佳处方：Soluplus与鞣花酸用量比为7.8∶1，制备温度为50 ℃，制备时间为1.6 h。自组装形成胶束的包封率为（94.62±1.12）%，载药量为（10.57±0.24）%，沉降率为（2.19±0.09）%，粒径为（68.90±6.87）nm，ζ电位为（−13.11±1.02）mV。鞣花酸以无定型形式存在于EA-SMSD粉末中，EA-SMSD在水及模拟胃、肠液中释药行为符合Weibull模型，且储存稳定性高。药动学结果显示，EA-SMSD达峰时间（t_max）延后至（5.15±0.98）h，达峰浓度（C_max）提高至4.03倍，相对口服吸收生物利用度提高至6.03倍。结论 EA-SMSD制备工艺简单，可显著增加鞣花酸相对口服吸收生物利用度。

Objective To prepare ellagic acid-loaded self-micelle solid dispersion (EA-SMSD), and study drug release in vitro and oral pharmacokinetic behaviors in vivo. Methods Encapsulation efficiency, drug loading and sedimentation rate of self-assembled micelles acted as evaluation indexes, formulation of EA-SMSD was optimized by Box-Behnken design-response surface method. Morphology of self-assembled micelles was observed by transmission electron microscopy (TEM), and crystal form of ellagic acid in EA-SMSD powder was analyzed by X-ray powder diffraction (XRPD). Drug release behaviors of ellagic acid from EA-SMSD in water and simulated gastrointestinal fluid were also investigated. Using ellagic acid as control, oral pharmacokinetic behavior of EA-SMSD was also compared. Results Optimal preparation of EA-SMSD: Soluplus to ellagic acid ratio was 7.8:1, preparation temperature was 50 ℃ and preparation time was 1.6 h. Encapsulation efficiency, drug loading, sedimentation rate, particle size and ζ potential of the self-assembled micelles were (94.62 ± 1.12)%, (10.57 ± 0.24)%, (2.19 ± 0.09)%, (68.90 ± 6.87) nm and (−13.11 ± 1.02) mV, respectively. Ellagic acid existed as an amorphous form in EA-SMSD powder. Drug release behaviors of EA-SMSD in water and simulated gastrointestinal fluid were conformed to Weibull model, and the storage stability was high. Pharmacokinetic results showed that t_max of EA-SMSD was delayed to (5.15 ± 0.98) h, C_max was increased to 4.03 times, and its relative bioavailability was increased to 6.03 times. Conclusion The preparation process of EA-SMSD was simple, and EA-SMSD could significantly increase the relative oral bioavailability of ellagic acid.

R283.6

国家教育部产学合作协同育人项目（2206005410900332）；亳州市重点研发计划（bzzc2021044）；普通高等学校学科专业建设资助项目（2020162001），河南省一流本科专业（药学）（202007387）