Solvent effects, solvation behavior, and thermodynamics of artesunate in alcohol-water mixtures

Abstract

The solubility of Artesunate (ART) in three different alcohol-water solvent mixtures was investigated using the KAT-LSER model. These mixtures were methanol (MeOH) + water, ethanol (EtOH) + water, and 2-propanol (2-PrOH) + water.  Hydrogen bond acidity (α), hydrogen bond basicity (β), the cavity term, and solvent polarity were the primary factors influencing solubility.  The parameter  was obtained by applying the inverse Kirkwood-Buff integrals (IKBI) approach to analyze the preferential ART solvation. The findings of this study demonstrate that artesunate (ART) is preferentially solvated by water in binary mixtures of alcohol and water, indicating a stronger local interaction between ART molecules and water than with alcohol. To better understand the dissolution behavior of ART, important thermodynamic characteristics, including dissolution and transfer enthalpy, Gibbs free energy, and entropy, were carefully investigated for a range of solvent compositions. The evaluation of these parameters and an enthalpy–entropy compensation analysis revealed that changes in ART solubility within the alcohol (1) + water (2) mixtures are mainly controlled by enthalpy, highlighting the energetic contributions of solute–solvent interactions. Such knowledge is essential for guiding solvent selection and formulation strategies, ultimately enhancing ART’s bioavailability, therapeutic performance, and stability in pharmaceutical and personal care product development.

KEY WORDS: Artesunate, Mixed solvents, Solvent effect, IKBI method, Preferential solvation

Bull. Chem. Soc. Ethiop. 2026, 40(1), 253-269.                                                          

DOI: https://dx.doi.org/10.4314/bcse.v40i1.20