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

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 (nicoti-namide). Comprehensive characterization containing morphology, hygroscopicity, solubility, fluores-cence 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 rang -ing from violet to indigo to green. Form IV and cocrystal with slip plane structures exhibited superior ten -sile 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 under-standing of the structure-property relationship of drugs in complex polymorphic systems. (c) 2023 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.