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

Journal of Pharmaceutical Sciences
Brian SamasBrian P Chekal

Abstract

There are two major challenges in developing a solid form: (1) identifying the thermodynamically stable form and (2) determining the method used to crystallize that form. Often experiments performed to address these challenges have different objectives and use separate experimental techniques. The thermodynamically stable form is usually found on small scale, utilizing slurries or crystallizations. Subsequently, a crystallization process is developed to purge impurities and to increase yield and these experiments are typically conducted on medium to large scale (greater than 10  g). Axitinib, a research compound for the treatment of cancer, forms solvates in most solvents to which it is exposed, presenting a problem in discovering and making a desirable anhydrous phase. A method has been developed that will give the best chance of making a thermodynamic stable form of the anhydrous material, necessarily not a desolvated form. This approach relies on solvent mediated transformation (thermodynamic control), rather than crystallization or solid-to-solid phase desolvation (generally kinetic control). Experimental conditions (a desolvation window) to produce an anhydrous solid form for this compound that shows predominance for solva...Continue Reading

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Citations

Jan 1, 2011·Annual Review of Chemical and Biomolecular Engineering·Alfred Y LeeAllan S Myerson
Jul 24, 2012·Journal of Pharmaceutical Sciences·Yuriy A AbramovAndreas Klamt
Jan 21, 2014·Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials·Srinivasulu AitipamulaReginald B H Tan

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