Favipiravir - Moxifloxacin ionic interaction to form a new antiviral – Antibiotic multicomponent system with the stability, potency, and safety enhancement
Abstract
Antivirals are commonly used in combination with antibiotics to treat infectious diseases; however, studies of their multicomponent systems are rarely reported. This experiment aimed to investigate the interaction between the antiviral favipiravir (FAV), a first-line COVID-19 drug, and the antibiotic moxifloxacin (MX). First, the appropriate stoichiometric interaction between the two drugs was screened. Afterward, their multicomponent system was prepared via solvent-drop grinding (SDG) at the predicted molar ratio. The SDG product was then characterized using differential scanning calorimetry and powder X-ray diffractometry. Next, the two-dimensional structure was elucidated by Fourier-transform infrared spectroscopy and completed by single-crystal X-ray diffractometry. Subsequent experiments focused on physicochemical properties, antibiotic potency, and an in silico toxicity study. Results showed that FAV reacted ionically with MX, forming a multicomponent system with new characteristics. That antiviral-antibiotic FMX multicomponent system was determined to be entirely a salt hydrate, thereby enhancing the short-term stability and antibiotic potency of MX, as semi-quantitatively assessed using microdilution methods. It was computationally predicted in silico that this may reduce the toxicity of the single drug using ProTox-3.
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