Use of Mechanochemical Methodology to Explore the Formation of a New Crystalline Phase in the Curcumin‐Quercetin System

Abstract

This study addressed the formation of co-crystals from Quercetin and Curcumin by mechanochemical treatment employing ball mill grinding. The binary system was initially studied using molecular complementarity and hydrogen bond propensity analysis structural tools available in Mercury software. This study was performed from CCDC reported structural data for Curcumin and Quercetin dihydrate used as starting reagents. Reaction conditions, such as Quercetin: Curcumin molar ratio, grinding time, and solvent-assisted variables, were optimised to synthesise a new solid phase from the binary system. The synthesised product was characterised by differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and powder X-ray diffraction techniques. Finally, to compare the anti-oxidant capacities from the pure components, eutectic mixtures previously reported and the new crystalline phase was evaluated in vitro using the 1,1-diphenyl-2-pycril-hydrazylhydrate radical inhibition method. The co-crystal phase and eutectic mixtures present higher anti-oxidant activity with values around 5.0 mg/L compared to pure Quercetin (3,444 mg/L) and Curcumin (9,141 mg/L), using only half of the molecules. These results indicate Quercetin molecule is synergically active with the Curcumin molecule in the binary mixtures.