Deciphering Imatinib Multicomponent Crystals: Insights from X-Ray Crystallography and Solid-State NMR Spectroscopy

We focused on the critical role of crystallization of active pharmaceutical ingredients (APIs) in drug development, with particular emphasis on stability, solubility, and the feasibility of drug formulation and manufacturing. We explored polymorphism in APIs and the formation of multicomponent crystals, including salt and cocrystal screening, underscoring the significance of regulatory and intellectual property considerations in recognizing salts and cocrystals of solid forms. Our study led to the design of seven new multicomponent crystalline forms of imatinib, an oncology API. Using X-ray crystallography and solid-state NMR, we elucidated hydrogen bonding interactions and proton transfer, unveiling multicomponent interactions in the crystalline solid forms along the salt–cocrystal continuum. Most of the new solid forms demonstrated improved aqueous solubility compared to that of the free base form. This research provides valuable insights into the structural details of solid forms of pharmaceutical compounds and emphasizes the importance of understanding solid-state interactions for the rational design of crystalline APIs, thereby enhancing the drug development process.