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

• Published in: Journal of molecular structure 2023-09, Vol.1288, p.135786, Article 135786
• Main Authors: Shang, Xinyue, Fu, Mingwei, Cai, Zhuoer, Wei, Lai, Ge, Shuwang, Ge, Min, Wang, Yihong
• Format: Article
• Language: English
• Subjects: Novel pharmaceutical; Rebamipide; Solubility
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135786

•One novel pharmaceutical salt and two solvates of rebamipide were successfully achieved.•This is the first report of a single crystal structure of rebamipide potassium salt and rebamipide ethanol solvate.•Rebamipide salt and solvates all showed better solubility and had great potential in the clinical applications of rebamipide. One rebamipide (REB) potassium salt REB·K·2EtOH (1), and two REB solvates with ethanol (EtOH) and dichloromethane (DCM), namely REB·EtOH (2) and REB·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 π-π 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.