A thermodynamic-based approach to analyzing a highly solvating polymorphic system: the desolvation window method.

Area of Science:

• Solid-state chemistry
• Pharmaceutical development
• Crystallization science

Background:

• Developing stable solid forms is crucial for drug development, facing challenges in identifying thermodynamic stability and crystallization methods.
• Axitinib, an anti-cancer compound, readily forms solvates, complicating the isolation of a desirable anhydrous phase.
• Current methods often use separate experiments for stability and process development, potentially missing the true stable form.

Purpose of the Study:

• To develop a method for identifying and producing the thermodynamically stable anhydrous form of Axitinib.
• To overcome the challenge of Axitinib's propensity to form solvates.
• To detail experimental conditions for achieving anhydrous solid form production.

Main Methods:

• Utilized solvent-mediated transformation (thermodynamic control) for solid form development.
• Focused on creating a 'desolvation window' to favor anhydrous form production.
• Employed techniques distinct from typical crystallization or solid-to-solid desolvation (kinetic control).

Main Results:

• Successfully developed a method to produce the thermodynamically stable anhydrous form of Axitinib.
• The method relies on thermodynamic control, specifically solvent-mediated transformation.
• Detailed experimental conditions (desolvation window) that favor anhydrous form over solvates were established.

Conclusions:

• Solvent-mediated transformation is an effective strategy for obtaining thermodynamically stable anhydrous forms, especially for compounds prone to solvation.
• The developed method provides a reliable approach to isolate the desired anhydrous Axitinib solid form.
• Understanding and controlling the 'desolvation window' is key to overcoming solvate formation challenges in solid form development.