Crystal engineering of curcumin with salicylic acid and hydroxyquinol as coformers

Abstract

Curcumin is a pharmaceutically viable ingredient derived from the rhizome of the Indian spice turmeric (Curcuma longa). However, curcumin suffers from poor water solubility, which limits its bioavailability. In this work, we report studies carried out to investigate cocrystallization of curcumin to improve its aqueous solubility. Salicylic acid and hydroxyquinol were used as coformers. Binary phase diagrams were constructed for curcumin–salicylic acid and curcumin–hydroxyquinol systems using differential scanning calorimetric (DSC) thermograms obtained for mixtures prepared by solid-state grinding. The curcumin–salicylic acid system was found to form an eutectic at a curcumin mole fraction of 0.33, whereas the curcumin–hydroxyquinol system clearly exhibited a cocrystal forming region. Out of the several curcumin to hydroxyquinol ratios studied, cocrystal formation was observed for mixtures containing curcumin mole fractions of 0.33 and 0.5. These curcumin–hydroxyquinol cocrystals were further characterized by powder X-ray diffraction analysis, DSC, scanning electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and solid-state 13C nuclear magnetic resonance spectroscopy. Intramolecular hydrogen bonding interactions in salicylic acid and weaker intermolecular interactions between hydroxyl (-OH) group present at the ortho position of salicylic acid with the keto (-C═O) group of curcumin result in a generation of eutectic, whereas strong hydrogen bonding interactions between hydroxyl -OH groups present in hydroxyquinol molecule and curcumin molecule result in formation of cocrystal upon melting and recrystallization. These curcumin–salicylic acid eutectic and curcumin–hydroxyquinol cocrystals show faster powder dissolution rates than raw curcumin. In the case of curcumin–hydroxyquinol cocrystals, cocrystals containing a curcumin mole fraction of 0.33 showed enhanced dissolution than cocrystals containing a curcumin mole fraction of 0.5.