Chongqing Academy of Chinese Materia Medica, Chongqing, China.
School of Pharmacy, Chengdu University of TCM, Chegndu, China.
Drug Deliv. 2023 Dec;30(1):2168794. doi: 10.1080/10717544.2023.2168794.
The aim of this study is to demonstrate a method for improving the solubility and relative bioavailability of artemisinin using a self-emulsifying drug delivery system (SEDDS). The self-emulsifying drug load, solubility, and emulsifying time were used as the evaluation indices, based on a solubility test and a ternary phase diagram. Optimal Mixture Design in Design-Expert software was used to optimize the prescription of the artemisinin SEDDS. By determining the water distribution coefficient combined with the drug concentration-time curve , a comparison was made of the relative oral bioavailability of the artemisinin SEDDS and the crude drug. The optimal prescription ratio of oleic acid polyethylene glycol glyceride, polyoxyethylene hydrogenated castor oil, and diethylene glycol monoethyl ether in the artemisinin SEDDS was 0.5:0.2:0.3 (wt/wt/wt), with a drug loading capacity of 41.556 mg/g, a solubility of 1.997 mg/mL, and a self-emulsification time of 214 s. The optimal prescription was transparent, slightly yellow, and oil-like. The average loading capacity of artemisinin was 41.912 mg/g, the emulsification time was 231 s, the average particle size was 128.0 nm, the average Zeta potential was -4.29 mV, and the solubility of artemisinin SEDDS in water was 1.997 mg mL. It is 33.85 times of the solubility of artemisinin in water, which achieves the purpose of increasing the solubility of artemisinin. The comparison of the oil/water distribution coefficient of the artemisinin SEDDS with that of the crude drug showed that SEDDS could improve the permeability of artemisinin and promote the absorption , and the relative bioavailability of the SEDDS agent was at least 1.47 times higher than that of the crude drug. The artemisinin SEDDS could significantly improve the solubility and relative bioavailability of artemisinin.
本研究旨在展示一种使用自乳化药物传递系统（SEDDS）来提高青蒿素溶解度和相对生物利用度的方法。基于溶解度试验和三元相图，使用自乳化药物载药量、溶解度和乳化时间作为评价指标。利用 Design-Expert 软件中的最佳混合物设计优化青蒿素 SEDDS 的处方。通过确定油水分配系数 并结合药物浓度-时间曲线 ，比较了青蒿素 SEDDS 和原料药的相对口服生物利用度。青蒿素 SEDDS 中油酸聚乙二醇甘油酯、聚氧乙烯氢化蓖麻油和二乙二醇单乙基醚的最佳处方比例为 0.5:0.2:0.3（wt/wt/wt），载药量为 41.556 mg/g，溶解度为 1.997 mg/mL，自乳化时间为 214 s。最佳处方为透明、微黄色、油状。青蒿素的平均载药量为 41.912 mg/g，乳化时间为 231 s，平均粒径为 128.0 nm，平均 Zeta 电位为-4.29 mV，青蒿素 SEDDS 在水中的溶解度为 1.997 mg/mL，是青蒿素在水中溶解度的 33.85 倍，达到了提高青蒿素溶解度的目的。青蒿素 SEDDS 与原料药的油水分配系数比较表明，SEDDS 可以提高青蒿素的通透性，促进吸收 ，SEDDS 制剂的相对生物利用度至少是原料药的 1.47 倍。青蒿素 SEDDS 能显著提高青蒿素的溶解度和相对生物利用度。
