Screening of Binary Solvent Mixtures and Solvate Formation of Indomethacin

The applicability of solubility parameters and solvent activity in the screening of binary solvent mixtures was studied. The solubility of indomethacin was measured in binary mixtures of dichloromethane, acetone, and ethyl acetate with methanol and ethanol. Solubility extremes in the mixed solvents were observed. The solubility maxima were related to the excess Gibbs free energy of the solvents and the hydrogen bonding term of the Hansen solubility parameter. The solvates of indomethacin were characterized with a confocal Raman spectrometer, and the desolvation of the solvates was investigated with thermogravimetry. The solubility of indomethacin was measured in binary mixtures of dichloromethane, acetone, and ethyl acetate with methanol and ethanol. The increased solubility observed in the mixed solvents correlates with the hydrogen bonding term of the Hansen solubility parameter and with the excess Gibbs free energy of the solvent mixtures, so these parameters can be applied for the screening of solvent mixtures.