Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C₁₇H₁₉F₃N₃O₃·C₄H₅O₆·2(H₂O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.