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Haibin Qu,Zhonghua Li,Guimin Zhang,Zongyi Zhou,Songgu Wu 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.124 No.-
Crystal engineering is a radical method to modulate the physicochemical properties of the drugs to meetthe needs of the pharmaceutical industry. Examined herein are six axitinib solid-state forms, includinganhydrous forms (Ⅳand XLI), solvates (acetic acid, nitromethane and n-propanol), and cocrystal (nicotinamide). Comprehensive characterization containing morphology, hygroscopicity, solubility, fluorescenceand powder tabletability were performed. Calculations of lattice energy, packing coefficient andenergy framework rationalized the structure–property relationship of these six forms from the packinglandscape. This system illustrates that form IV and cocrystal improve the solubility of axitinib, but thehumidity stability is also decreased. Six crystal forms show polychromatic solid-state luminescence rangingfrom violet to indigo to green. Form IV and cocrystal with slip plane structures exhibited superior tensilestrength and compactibility than isotropic form XLI. Elusive form VI can be obtained by controllingthe humidity levels during desolvation of the solvate. This work not only realizes the regulation of betterphysicochemical properties of axtinnib for industrial manufacturing, but also provides a detailed understandingof the structure–property relationship of drugs in complex polymorphic systems.
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