Real-time co-crystal screening and formation between indomethacin and saccharin via DSC analytical technique or DSC–FTIR microspectroscopy

Abstract

A tool for quick screening co-crystal formation between indomethacin (IMC) and saccharin (SAC) was attempted using DSC analytical technique or DSC–FTIR microspectroscopy as an accelerated method. The solid-state characterizations of IMC, SAC, and their physical, 30-min ground, or solvent-evaporated mixture, were, respectively, investigated. The DSC data evidences that two endothermic peaks at 154 and 184 °C but one exothermic peak at 158 °C were observed in the DSC curve of the physical mixture of IMC–SAC. The former appeared at 154 °C might be due to the fusion of eutectic mixture, but the latter at 184 °C was corresponded to the melting point of IMC–SAC co-crystal following the exothermic peak at 158 °C. The exothermic peak at 158 °C was due to the induction of molecular interaction of IMC and SAC, leading to IMC–SAC co-crystal formation. This indicates that DSC analytical technique could directly detect the thermal changes of the physical mixture of IMC–SAC to form an IMC–SAC co-crystal. Once the temperature was beyond 154 °C after determination with DSC–FTIR microspectroscopy, several new IR absorption peaks at 3165, 1736, 1684, 1319, 1221, and 1176 cm−1 due to the IMC–SAC co-crystal formation via an intermolecular interaction were simultaneously observed from the thermal-dependent three-dimensional FTIR spectral contour. This one-step DSC–FTIR microspectroscopic system giving thermodynamic and spectroscopic information could easily and directly screen and detect the IMC–SAC co-crystal formation in real time.