Multicomponent Crystal Screening and Performance Testing of Sunitinib: A Combined Virtual and Experimental Study

Sunitinib (STN), a critical anticancer drug, has attracted significant clinical attention due to its therapeutic potential. This study aims to improve the pharmaceutical performance of sunitinib by designing multicomponent crystals. A combined virtual and experimental approach was employed for the screening of multicomponent crystals. Full Interaction Maps (FIM) were used to analyze the molecular structure of STN, leading to the identification of 60 potential coformers. Virtual screening was conducted using the Conductor-like Screening Model for Real Solvents (COSMO-RS), Cambridge Structural Database (CSD) Molecular Complementarity (MC) analysis, and Hansen Solubility Parameters (HSP). The hit rates for potential coformers were 59.09% for COSMO-RS, 22.22% for MC, and 40.74% for HSP. From these, 28 new phases were discovered, and five multicomponent crystals of STN were structurally characterized via single-crystal X-ray diffraction (SCXRD). These crystals exhibited enhanced solubility and altered hygroscopic properties, as confirmed through equilibrium and powder dissolution measurements, dynamic vapor sorption (DVS), and accelerated stability tests. Additionally, molecular interaction and packing analysis were conducted to elucidate the interaction mechanisms, providing insights into the improved solubility and stability of STN in multicomponent crystals. Dissolution behavior was further explained using molecular volume-normalized hydration-free energy and lattice energy calculations. This study offers novel strategies for enhancing the clinical application of sunitinib through crystal engineering.