Effect of Cosolvents on the Solubility of Lenalidomide and Thermodynamic Model Correlation of Data

It is well known that cosolvency is one of the best techniques employed in physical chemistry for improving solubility of drugs. The solubility data in (acetonitrile + methanol), (acetonitrile + isopropanol), (ethyl acetate + methanol), and (ethyl acetate + isopropanol) binary solvents with cosolvent (acetonitrile and ethyl acetate) mole fraction ranging from 0 to 1 at various temperatures ranging from 273.15 to 318.15 K was measured and correlated by the Jouyban–Acree model and CNIBS/R–K model. The results showed that solubility of lenalidomide increased with the increasing temperature, while increased with growing cosolvent mass fraction (w) to a maximum value at w = 0.6 and then decreased in all four tested binary solvent systems. Under the same temperature and solvent ratio, the solubility values obey the following order: (acetonitrile + methanol) > (ethyl acetate + methanol) > (acetonitrile + isopropanol) > (ethyl acetate + isopropanol). Moreover, by comparing the calculated and experimental values of the model and residual analysis, it can be seen that the CNIBS/R–K model is more suitable for correlating the solubility data of lenalidomide in these four mixed solvents. The discovery of cosolvency phenomenon is important to optimize the preparation and purification of lenalidomide.