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.

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

“…14,31 A recent report describes many co-crystals of this molecule. 32 To analyze the solid-state, we have grown the crystals of M7 from chloroform by the slow evaporation method. The data was the same as that reported by Shi et al in 2014.…”

Soot-Based Reduced Graphene Quantum Dot/Hemin Conjugate for Favipiravir Sensing

“…As Fav shows weak solution-phase fluorescence, cocrystals of Fav will definitely affect its photophysical property. In a very recent report, we investigated the physicochemical properties of a few cocrystals of Fav with generally regarded as safe (GRAS) coformers . From the reported cocrystal system, we selected two Fav cocrystals, viz.…”

“…In a very recent report, we investigated the physicochemical properties of a few cocrystals of Fav with generally regarded as safe (GRAS) coformers. 48 From the reported cocrystal system, we selected two Fav cocrystals, viz. 1:1 cocrystals of Fav•Theo and Fav•FRA, which showed significant changes in fluorescence intensity (Figure S9).…”

Exploring the permeability of covid-19 drugs within the cellular membrane: a molecular dynamics simulation study

“…In this respect, we have performed the MD simulation to investigate the interaction and permeability of the FAV and HCQ drugs with the cellular membrane. While extensive studies have been performed on the FAV and HCQ drugs, 23–28 published works concerning the interactions of FAV and HCQ drugs with and diffusion through phospholipid membrane are still scarce. Consequently, we aim to unravel how these drugs adsorb and penetrate through the cellular membranes.…”