Solubility Behavior and Data Correlation of Quinidine in Twelve Pure Solvent Systems

Abstract

The equilibrium mole-fraction solubility of quinidine in 12 pure organic solvents was determined by a static gravimetric method at 283.15–323.15 K and atmospheric pressure (293.15–333.15 K for dimethyl sulfoxide and 1,4-dioxane, owing to their high freezing points). The solubility increases monotonically with temperature in every solvent and is highest in 1-butanol and lowest in acetonitrile. The experimental data were correlated with the modified Apelblat and Yaws models, which give essentially equivalent accuracy, with overall mean average relative deviations (ARD) of 2.00% and 2.02% and mean root-mean-square deviations (RMSD) of 1.05 × 10–3 and 1.06 × 10–3, respectively; the residuals show no systematic deviation with temperature. A van’t Hoff analysis gives apparent dissolution enthalpies of 6.63–32.46 kJ·mol–1 and positive apparent Gibbs energies, indicating endothermic dissolution in all systems. Hirshfeld surface analysis shows that H···H and O···H/H···O contacts contribute 26.7% and 23.2% of the total intermolecular contacts in the crystal. The solvent effect was analyzed in terms of the ET(30) polarity parameter, hydrogen-bond donor/acceptor propensities, and cohesive energy density, and no single descriptor is sufficient to explain the solvent ranking. The data set provides a thermodynamic basis for solvent screening and for the design of quinidine crystallization and purification processes.