Solvates and Polymorphs of Axitinib: Characterization and Phase Transformation

Area of Science:

• Pharmaceutical Chemistry
• Solid-State Chemistry
• Materials Science

Background:

• Axitinib (AXTN) is a crucial tyrosine kinase inhibitor for renal cell carcinoma treatment.
• Understanding the solid-state properties of AXTN, including solvates and polymorphs, is vital for drug formulation and efficacy.
• Previous research has not fully explored the solvate formation and phase transformations of AXTN.

Purpose of the Study:

• To prepare and characterize solvates of axitinib (AXTN) in various solvents.
• To investigate the desolvation processes and identify new crystal forms of AXTN.
• To elucidate the phase transformation pathways of AXTN solvates under different conditions.

Main Methods:

• Solvate preparation of AXTN in acetonitrile, DMF, acetic acid, acetic acid + water, and methanol.
• Solid-phase desolvation (heating, solvent steam, microwave) and solvent-mediated phase transformation (SMPT).
• Characterization using PXRD, TGA, DSC, FT-IR, and SEM.

Main Results:

• Five types of AXTN solvates were successfully prepared and characterized.
• A novel crystal form (form Z) of AXTN was obtained after desolvation.
• Mutual transformations between solvates were observed via SMPT, influenced by solvent composition.

Conclusions:

• The study successfully identified new solvates and a novel crystal form (form Z) of axitinib.
• Understanding AXTN solvate behavior and phase transitions is critical for developing optimized drug formulations.
• The findings provide valuable guidance for exploring further polymorphs and solid-state properties of axitinib.