Development of a liquid formulation of poorly water-soluble isosteviol sodium using the co-solvent technology

Abstract

An intravenously injectable liquid formulation of the poorly water-soluble isosteviol sodium (ISVNa) that has a great clinical potential for cardiovascular diseases was developed using the co-solvent technology. The pH and composition of the co-solvent were optimized to obtain a stable liquid formulation (termed as STVNa) based on saline at pH 10.0 containing 25% (v/v) of ethanol and 20% (v/v) of propylene glycol. STVNa was physicochemically stable upon storage for more than 3 months under various conditions. In vitro studies showed that STVNa did not induce hemolytic effects up to 9.1% (v/v) after 3 h of incubation and it was cytocompatible up to 50 μg/mL in H2C9 cells. Furthermore, STVNa showed acceptable safety and pharmacokinetic parameters comparable with those of ISVNa in saline (dissolved at 60 °C) upon i.v. injection in Wistar rats. Overall, the results demonstrated that STVNa is a promising formulation of ISVNa for clinical translation.

Keywords:

• Isosteviol sodium
• liquid formulation
• intravenous injection
• poorly water soluble
• co-solvent

Acknowledgements

The authors thank Key-Pharma Biomedical Inc. for providing ISVNa and Jingu Packaging Material Co., Ltd. for donating the ampoules.

Disclosure statement

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