Solubility Determination and Correlation of Warfarin Sodium 2‑Propanol Solvate in Pure, Binary, and Ternary Solvent Mixtures

The solubility of warfarin sodium isopropanol solvate (WS·IPA), a widely used anticoagulant, was determined at temperatures ranging from 278.15 to 333.15 K in four pure solvents (acetone, ethanol, IPA, and water), five binary solvent mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary solvent mixtures (IPA + acetone + heptane, IPA + acetone + hexane, IPA + ethanol + heptane, IPA + ethanol + hexane, and IPA + water + heptane) using the polythermal method. It was demonstrated that the solubility of WS·IPA increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. In addition, the solubility of WS·IPA in IPA increases with increasing content of acetone, ethanol, and water, which act as cosolvents, and decreases with increasing content of heptane and hexane, which act as antisolvents. The experimental solubility data of WS·IPA in pure solvents and binary and ternary solvent mixtures were correlated using the modified Apelblat and λh model equations. The correlated solubility data agree with the experimental data based on the relative deviation and the average relative deviation (ARD %) values. Thus, the correlated and experimentally derived solubility data of WS·IPA provide a pathway to engineer advanced pharmaceutical crystallization processes for WS·IPA.