Improvement of in vitro and in vivo properties of nilotinib-flavonoid drug-drug cocrystals: synergistic effect

Four nilotinib-flavonoid drug-drug cocrystals were successfully prepared. • NIL-BAI cocrystal exhibited the most significant dual solubility enhancement. • NIL-BAI cocrystal improved nilotinib and baicalin bioavailability in rats. • Drug-drug cocrystals overcome the physicochemical limitations of nilotinib. This study employs a supramolecular cocrystallization strategy to simultaneously enhance the pharmaceutical performance of the poorly water-soluble anticancer drug nilotinib and pharmacologically active flavonoids. Four nilotinib cocrystals were successfully prepared via slurry and room-temperature solvent evaporation methods, using kaempferol, quercetin, baicalin, and luteolin as coformers. The four cocrystals exhibited varying degrees of solubility enhancement. Among them, the nilotinib-baicalin cocrystal demonstrated the most significant dual enhancement effect. Specifically, nilotinib solubility increased by 6.19-fold and baicalin by 1.88-fold at pH 6.8, with corresponding enhancements of 2.06-fold and 47.74-fold at pH 1.2. Critically, pharmacokinetic evaluations in rats revealed that the nilotinib-baicalin cocrystal achieved dual bioavailability enhancement: nilotinib exhibited a 9.48-fold higher C max and a 6.78-fold greater AUC 0–24h , while BAI concurrently demonstrated a 2.1-fold and 2.86-fold increase in its C max and AUC 0-24h , respectively. Overall, this work highlights drug-drug cocrystallization as a highly effective approach for developing multifunctional formulations, offering a promising strategy to overcome the physicochemical limitations of nilotinib and improve therapeutic efficacy. Download: Download high-res image (294KB) Download: Download full-size image