Tuning the physicochemical properties of axitinib by crystallization: Preparation, calculation and Structure-property relationship

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) Vol. 124; pp. 570 - 578
• Main Authors: Qu, Haibin, Li, Zhonghua, Zhang, Guimin, Zhou, Zongyi, Wu, Songgu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.08.2023; 한국공업화학회
• Subjects: Anticancer drugs; Multicomponent crystals; Powder properties; Solid-state chemistry; Structure-property relationship; 화학공학; Anticancer drugs; Solid-state chemistry; Multicomponent crystals; Structure-property relationship; Powder properties
• ISSN: 1226-086X; 1876-794X
• DOI: 10.1016/j.jiec.2023.05.014

[Display omitted] •Six solid forms of axitinib were systematically evaluated for their physicochemical properties.•Theoretical and experimental studies were performed to rationalize structure–property relationship.•Tiny changes in crystal structure will cause unforeseen obstacles at any stage of the development and production process.•The elusive crystal form VI was prepared by controlling the conditions of desolvation. Crystal engineering is a radical method to modulate the physicochemical properties of the drugs to meet the needs of the pharmaceutical industry. Examined herein are six axitinib solid-state forms, including anhydrous forms (Ⅳ and XLI), solvates (acetic acid, nitromethane and n-propanol), and cocrystal (nicotinamide). Comprehensive characterization containing morphology, hygroscopicity, solubility, fluorescence and powder tabletability were performed. Calculations of lattice energy, packing coefficient and energy framework rationalized the structure–property relationship of these six forms from the packing landscape. This system illustrates that form IV and cocrystal improve the solubility of axitinib, but the humidity stability is also decreased. Six crystal forms show polychromatic solid-state luminescence ranging from violet to indigo to green. Form IV and cocrystal with slip plane structures exhibited superior tensile strength and compactibility than isotropic form XLI. Elusive form VI can be obtained by controlling the humidity levels during desolvation of the solvate. This work not only realizes the regulation of better physicochemical properties of axtinnib for industrial manufacturing, but also provides a detailed understanding of the structure–property relationship of drugs in complex polymorphic systems.