Crystal Structure and Enhanced Physicochemical Properties of a Famotidine−Saccharin Salt

A hydrated salt crystal comprising famotidine (FMT) and saccharin (SAC) was synthesized via liquid-assisted grinding and solvent evaporation. Single-crystal X-ray diffraction results revealed that the FMT−SAC salt crystallized in the triclinic space group P-1, comprising an FMT cation, SAC anion, and water molecule in each asymmetric unit. The structure features a distinct layered packing motif, stabilized by a hydrogen bonding network with R22(8), R22(10), and R44(34) motifs, while water molecules function as bridges. FMT−SAC exhibited significantly improved physicochemical properties with 5- and 9-fold higher aqueous solubility and intrinsic dissolution rates, respectively, than pure FMT. Tableting performance of FMT−SAC was remarkably enhanced. Moreover, the FMT−SAC tablet prevented capping under strong compaction forces. These improvements were attributed to the exposure of a hydrophilic surface of the salt with low attachment energy and a slip plane owing to the presence of lattice water molecules. This study establishes a structure−property relation, highlighting the utility of salt formation and hydrate engineering for enhancing the solubility and mechanical performance of poorly compressible drugs.