Solubility Determination, Solute-Solvent Interactions, and Model Correlation of Sorafenib in Twelve Pure Organic Solvents between T=273.15 and 313.15 K

The isothermal saturation method was applied to study the solubility of sorafenib free base in 12 pure solvents in the temperature range from 273.15 to 313.15 K under atmospheric pressure. The solubility in selected solvents increased with the increasing temperature. The maximum mole solubility was in cyclohexanone (2.512 x 10(-2)) at 313.15 K, followed by in 2-butanone (1.334 x 10(-2)), acetone (5.577 x 10(-3)), toluene (4.282 x 10(-3)), ethyl acetate (2.930 x 10(-3)), n-propanol (2.067 x 10(-3)), 1-butanol (1.816 x 10(-3)), ethanol (1.554 x 10(-3)), isopropanol (1.385 x 10(-3)), isobutanol (1.256 x 10(-3)), methanol (0.848 x 10(-3)), and acetonitrile (0.678 x 10(-3)). The quantitative solubility data of sorafenib free base in some pure and mixed organic solvents have been reported in the literature. However, the results were not satisfactory. There is an increase of 12.06-fold between cyclohexanone and n-propanol at 313.15 K. Hence, for sorafenib free base, the solubility can be improved not only in the form of salt, but also by the selection of a good solvent. In addition, the results obtained in 12 pure solvents were correlated with the modified Apelblat equation and the.h equation. The maximum of relative average deviation was 1.62% and obtained using the.h equation, which indicated that two equations could give satisfactory results in selected pure solvents.