Favipiravir-levofloxacin salt reaction and its impact on the physicochemical properties

Antivirals are often combined with antibiotics to treat infectious diseases, yet studies on their multicomponent systems remain limited. This experiment aimed to develop a multicomponent system combining the antiviral favipiravir (FAV) and the antibiotic levofloxacin (LF) and to investigate its effects on physicochemical properties, antibiotic potency, and toxicity. First, the stoichiometric ratio of the new compound was determined by thermal analysis and powder X-ray diffractometry, yielding a 1:1 molar ratio. Subsequently, FTIR analysis was performed to elucidate the 2D structure, followed by the determination of the 3D structure using single-crystal X-ray diffraction. The results showed that FAV reacted with LF via wet grinding, producing a new multi-component system (FAV-LF) with a distinct thermal profile and diffractogram. The structural data indicated that the multicomponent system was a salt, which exhibited greater stability but lower solubility than the individual components. Potency tests demonstrated that the salt enhanced the antibacterial activity of LF against Gram-positive bacteria, but had no effect against Gram-negative bacteria. Furthermore, based on toxicity test predictions, the FAV-LF salt exhibited reduced mutagenicity compared with LF alone and effectively mitigated blood-brain barrier toxicity relative to FAV alone. Therefore, comprehensive experiments can further develop dosage formulations of the FAV-LF salt.