Flavonoid-Based Cocrystals: A Comprehensive Study on Their Synthesis, Characterization, Physicochemical Properties and Applications

Flavonoids are naturally occurring compounds with reported anticancer, antimicrobial, anti-inflammatory, cardio-protective and antioxidant effects. They are increasingly incorporated in functional foods designed to promote health, enhance well-being, and support physical performance. However, their practical use is limited because of their low water solubility and poor absorption within the body. An effective strategy for developing new flavonoid-based formulations involves their transformation into molecular complexes (cocrystals) through cocrystallization, a method that has emerged a powerful tool to modulate the physicochemical and biological properties of polyphenols and other relevant drugs. Cocrystals are stabilized through non-covalent interactions, which can introduce new physicochemical properties to the original molecules (coformers) while retaining the chemical properties of the coformers, as no bonds are broken or formed. Flavonoid-based cocrystals can be obtained through a variety of methods using different coformers, and we aim here to review cocrystals containing flavonoids and coformers, with a focus on their methods of synthesis, physicochemical and biological characteristics, as well as their potential applications in both the food and pharmaceutical sectors.