目的 制备多潘立酮自乳化颗粒，考察其性质表征、在大鼠体内的药动学特征。方法 测定多潘立酮在不同辅料中的溶解度，结合配伍相容性实验和伪三元相图分析，确定多潘立酮自乳化释药系统的处方组成和比例，并以硅酸铝镁为惰性载体，将多潘立酮自乳化微乳转化为自乳化颗粒。评价了多潘立酮自乳化颗粒自乳化形成微乳的微观形态、粒径分布及其在模拟生理pH值介质中的稀释稳定性，比较了多潘立酮自乳化颗粒剂与多潘立酮颗粒剂的体外溶出率。采用大鼠在体肠灌注实验测定多潘立酮自乳化颗粒的肠吸收动力学参数，并考察了多潘立酮自乳化颗粒在大鼠体内的药动学特。结果 以Capmul MCM为油相、Tween 80为表面活性剂、Transcutol HP为助表面活性剂，按4∶3∶3的比例制备多潘立酮自乳化释药系统。多潘立酮自乳化颗粒所形成的微乳粒径分布较窄、均匀，且表面带较高负电荷，滴形态规整，多呈球形或类球形，分散性良好，在模拟生理pH值介质中稳定性良好；体外溶出结果显示，多潘立酮自乳化颗粒剂在模拟生理pH值介质中可实现药物的快速、完全释放；在大鼠体肠吸收实验证实，多潘立酮自乳化颗粒剂对肠道上皮屏障的穿透能力增强，进而有效促进了药物的跨膜转运。大鼠药动学结果表明，多潘立酮自乳化颗粒能够显著提高药物口服生物利用度。结论 多潘立酮自乳化颗粒可有效促进药物溶出，提高肠道吸收，增加口服生物利用度。

Objective To prepare domperidone self-emulsifying granules, and investigate its physicochemical characteristics and pharmacokinetic properties in rats. Methods The solubility of domperidone in various excipients was determined, and the formulation composition and proportions of the domperidone self-emulsifying drug delivery system were established by combining compatibility tests and pseudo-ternary phase diagram analysis. Using magnesium aluminum silicate as an inert carrier, domperidone self-emulsifying granules microemulsion was transformed into self-emulsifying particles. The microscopic morphology, particle size distribution, and dilution stability of the domperidone self-emulsifying particles in simulated physiological pH media were evaluated. The in vitro dissolution rates of the domperidone self-emulsifying particles and domperidone particles were compared. Rats were used in vivo intestinal perfusion tests to determine the intestinal absorption kinetic parameters of the domperidone self-emulsifying particles, and the pharmacokinetic characteristics of the domperidone self-emulsifying particles in rats were investigated. Results Domperidone self-emulsifying drug release system was prepared in a ratio of 4:3:3 using Capmul MCM as the oil phase, Tween 80 as the surfactant, and Transcutal HP as the co-surfactant. The microemulsion formed by domperidone self-emulsifying granules has a narrow and uniform particle size distribution, with a high negative charge on the surface, regular droplet morphology, mostly spherical or quasi spherical, good dispersibility, and good stability in simulated physiological pH media. The in vitro dissolution results showed that domperidone self-emulsifying granules can achieve rapid and complete drug release in a simulated physiological pH medium. In the rat intestinal absorption test, it was confirmed that domperidone self-emulsifying granules enhance the penetration ability of the intestinal epithelial barrier, thereby effectively promoting the transmembrane transport of the drug. The pharmacokinetic results of rats showed that domperidone self-emulsifying granules can significantly improve the oral bioavailability of the drug. Conclusion Domperidone self-emulsifying granules could effectively promote drug dissolution, enhance intestinal absorption, and increase oral bioavailability.

R975

湖北省卫生健康科研基金资助(WJ2021M218)