Mechanosynthesis, Characterization, and Physicochemical Property Investigation of a Favipiravir Cocrystal with Theophylline and GRAS Coformers

Abstract

Five cocrystals of antiviral drug favipiravir (Fav) with respiratory drug theophylline (Theo) and GRAS coformers, viz., p-aminobenzoic acid (PABA), 4-hydroxybenzoic acid (4HBA), gallic acid (GA), and ferulic acid (FRA), were successfully synthesized using mechanochemistry as well as solution crystallization. All the synthesized cocrystals were characterized using PXRD, SCXRD, and thermal analysis. A physicochemical property investigation showed an excellent correlation of coformer solubility with cocrystal solubility. Moreover, cocrystal solubility can be tuned based on the selection of coformers during cocrystallization as well as the pH of the medium. Crystal structure analysis depicts amide–amide homosynthon formation in the Fav·Theo cocrystal and an acid–amide heterosynthon in the case of cocrystals with GRAS coformers. Incorporation of nutraceuticals (GA and FRA) provides an additional health benefit, whereas Fav·Theo cocrystal may be a potential formulation to treat patients suffering from chronic obstructive pulmonary disease (COPD) or asthma along with viral infections.