Cocrystal Formation of Quercetin and Nutraceutical Coformers via a Facile Technique with Improved Solubility and Biological Properties

Cocrystallization has emerged as an effective strategy to improve the physicochemical and pharmaceutical properties of bioactive compounds. Here, we prepared novel cocrystals of quercetin (Que) and nutraceutical coformers, i.e., vitamin B6, inositol and l-carnitine, by using slurry methods. The cocrystals were characterized using orthogonal techniques, including scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), DSC, Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS), providing complementary insights into the morphology, crystallinity, thermal behavior, and molecular interactions and confirming the formation of distinct solid phases. Dissolution studies revealed markedly enhanced solubility and release rates up to 1.2-2.5-fold higher within the first hour compared to unmodified quercetin. In cell-based assays, all cocrystals exhibited improved cytotoxicity against cervical and lung cancer cells via apoptotic induction and effective ROS reduction while maintaining minimal toxicity toward normal cells. Among all cocrystals, the cocrystal between quercetin and l-carnitine (<b>QB11</b>) 'was the most potent against cervical cancer cells, whereas the cocrystal between quercetin and pyridoxine (<b>QB6</b>) and quercetin and inositol (<b>QB8</b>) cocrystals showed greater activity against lung cancer cells. Moreover, the <b>QB6</b> cocrystal demonstrated a superior ROS-scavenging efficacy, compared to unmodified quercetin. These findings highlight the potential of cocrystallization to develop safer, more effective formulations of quercetin and to overcome its solubility limitations.