The delivery of arbidol by salt engineering: synthesis, physicochemical properties and pharmacokinetics

Abstract

The aim of the present study was to evaluate the feasibility of using the methanesulfonic salt of arbidol in order to improve its aqueous solubility and thus oral bioavailability. Arbidol mesylate (AM) was synthesized and then characterized using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), and its apparent solubility and octanol–water partition coefficient were also studied. The results of NMR, IR, PXRD, SEM and DSC tests confirmed the salt formation. The apparent solubility of AM in water was 32-fold higher than that of the commercial product. A superior pH-dependent profile and an improved dissolution rate of AM were obtained in a variety of solutions with different pH values. In addition, AM exhibited a relatively higher peak plasma concentration (1460 versus 1297 ng/mL) and an increased AUC_0–t (2475 versus 1277 ng/mL × h) when comparing with the commercial product, indicating the improved bioavailability of the drug. This study suggests that AM may be able to improve the therapeutic efficacy of arbidol, which rendering it to be a promising candidate for further development.

Keywords:

• Arbidol mesylate
• arbidol hydrochloride monohydrate
• salt engineering
• physicochemical properties
• dissolution
• pharmacokinetics

Acknowledgements

The authors are very grateful to the Analytical Department of Shenyang Pharmaceutical University and the Institute of Metal Research of Chinese Academy Science for providing access to advanced techniques.

Disclosure statement

The authors report no declarations of interest. The authors alone are responsible for the content and writing of this article.