Challenge for improving metastable crystal quality of organic low molecules for drug development

Abstract

  We describe new methods for selective crystallization of the metastable phase of pharmaceutical compounds using a slow cooling method, polymer-induced heteronucleation (PIHn) and solution mediated transformation. New crystal seeding methods were also introduced, thus it became possible to control the supersaturations. These technology enabled us to improve quality of the metastable phase．Appropriate control of the form II crystal growth rate via slow cooling or solution mediated transformation suppressed the defect formation and improved the crystallinity of form II. These polymorphic control technologies are applicable to other materials, thus they have possibility to be practical applications in the future.