Co-solvence phenomenon and thermodynamic properties of edaravone in pure and mixed solvents

Abstract

The dissolution behavior of drugs in cosolvent mixtures is very important, especially in systems with co-solvence phenomenon. The solubility of edaravone in pure and mixed solvents was determined experimentally by using the isothermal dissolution equilibrium method within the temperature range from (273.15 to 313.15) K under atmosphere pressure (101.3 kPa). The maximum solubility was (4.72 × 10−2 in mole fraction) obtained at 313.15 K in n-propanol, and the minimum data was found at 273.15 K in acetonitrile. However, in mixed solvents, the solubility of edaravone increased with the increasing temperature, while increased with increasing co-solvent mass fraction (w) to a maximum value at w = 0.6 and then decreased, and Extended Hildebrand Solubility Approach was applied to explain this phenomenon. In addition, the solubility data obtained were correlated with the modified Apelblat equation, λh equation, Jouyban-Acree model and CNIBS/R-K model. The results indicated that the modified apelblat equation and Jouyban-Acree model are more suitable to correlate solubility data of edaravone in studied pure and mixed solvents, respectively. The apparent dissolution standard enthalpy (ΔHsolo), apparent molar standard Gibbs energy (ΔGsolo) and ΔSsolo of edaravone in pure and mixed solvents were also evaluated.