Sodium versus ammonium salts of a poorly water-soluble API using sparfloxacin - physicochemical and biological...

This study aimed to improve the solubility and delivery of sparfloxacin, a poorly soluble quinolone antibiotic, by forming ionic liquids (API-ILs) with hydrophilic quaternary ammonium salts differing in alkyl chain length and hydroxyl group presence. The resulting sparfloxacin-ILs (N6SPAR, N10SPAR, N6OHSPAR, N10OHSPAR) were synthesized with yield of (72 ± 6)% for N6SPAR, N10SPAR, N10OHSPAR and 44 % for N6OHSPAR. Solubility in water, ethanol, and 1-octanol was assessed using dynamic and spectrophotometric methods, with N6SPAR showing the highest water solubility. Differential Scanning Calorimetry (DSC) revealed differences in melting behavior among the derivatives. Lipid-based carrier studies indicated that longer alkyl chains enhance lipid incorporation, while hydroxyl groups reduce it. Biological assays showed no significant cytotoxicity, with cell viability remaining above 50 % at concentrations up to 200  µM, and preserved antibacterial activity, with MICs of 61  nM (E. coli), 488  nM (S. aureus), and 1950  nM (P. aeruginosa). Increased efficacy was observed for N6OHSPAR against E. coli (twofold) and reduced for N6SPAR against P. aeruginosa (fourfold). These findings highlight the potential of IL cation modification to fine-tune solubility and bioactivity, supporting their use in advanced drug formulations where conventional approaches are insufficient.