Novel pharmaceutical salt and solvates of rebamipide: Preparations, structural analysis and properties

One rebamipide (REB) potassium salt REB center dot K center dot 2EtOH (1), and two REB solvates with ethanol (EtOH) and dichloromethane (DCM), namely REB center dot EtOH (2) and REB center dot DCM (3), were synthesized in this work. The crystal structure, stability, thermal properties, and solubility of salt 1, solvate 2, and solvate 3 have been explored by various analytical techniques. Crystal structure analyses reveal that two-dimensional layered network of salt 1 was built by coordination with K+ and that three-dimensional framework of solvate 2 formed through hydrogen bonds network and pi-pi stacking. Hirshfeld surface and 2D fingerprint plots were obtained to further investigate the weak interaction between molecules. All of the crystals exhibited considerably enhanced aqueous solubility compared with the REB and had the potential in clinical applications.

Automated summary

In this study, one important drug salt and two solvates were synthesized, and their crystal structure, stability, thermal properties, and solubility were investigated using various analytical techniques. Crystal structure analyses showed that salt 1 formed a two-dimensional layered network through coordination with K+ and solvate 2 formed a three-dimensional framework through hydrogen bonds network and pi-pi stacking. Hirshfeld surface and 2D fingerprint plots were obtained to further study the weak interaction between molecules. All crystals exhibited significantly enhanced aqueous solubility compared to REB and had potential in clinical applications.