The preparation and relative bioavailability of an artemisin in self-emulsifying drug delivery system

Abstract

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 in vitro, combined with the drug concentration–time curve in vivo, 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^–1. 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 in vitro showed that SEDDS could improve the permeability of artemisinin and promote the absorption in vivo, 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.

Keywords:

• Artemisinin
• self-emulsifying drug delivery systems (SEDDS)
• ternary phase diagram
• central composite design-response surface methodology
• bioavailability

Ethics approval

This study was conducted with approval from the Ethics Committee of Chongqing Academy of Chinese Materia Medica (no. 20060801). This study was conducted in accordance with the declaration of Helsinki. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All methods are reported in accordance with ARRIVE guidelines

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Acknowledgment

We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

Availability of data and materials

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Author contributions

Conception and design of the research: Wang YH, Gao SJ, Zhang XM; Acquisition of data: Chen JC, Peng WQ; Analysis and interpretation of the data: Wang YH, Chen JC, Gao SJ; Statistical analysis: Wang YH, Chen JC, Hua L; Obtaining financing: Yang Yang, Yang Yong, Hua L, Guo YL; Writing of the manuscript: Wang YH, Chen JC, Gao SJ, Zhang XM; Critical revision of the manuscript for intellectual content: Wang YH, Zhang XM; All authors read and approved the final draft.

Additional information

Funding

Science and technology project of Chongqing Science and Technology Commission (cstc2019jxjl-jbky10002); the National Major New Drug Creation Major Science and Technology Projects (2017ZX09101002-002-004)