Nucleation Control and Separation of Stable and Metastable Polymorphs of L‐histidine Through Novel Swift Cooling Crystallization Process

Abstract

AbstractNucleation control, separation and crystal growth of polymorphic forms of the well‐known amino acid L‐histidine from pure aqueous solution is investigated by adopting the novel swift cooling crystallization process for the first time. The concomitant nucleation behavior of the stable orthorhombic and metastable monoclinic polymorphs of L‐histidine is investigated under different supersaturation conditions. While lower‐level of supersaturation favours the nucleation of stable polymorph, higher‐level supersaturation favours the nucleation of metastable polymorph of L‐histidine. By this way, the nucleated concomitant polymorphs of L‐histidine are separated successfully and grown as single crystals from pure aqueous solution without using any additives or anti‐solvents. Morphology of the nucleated polymorphs are identified through optical microscopy and confirmed by optical goniometry. Also, the morphological importance of different growth faces is evaluated. The distinction in the crystal system of the two polymorphs is identified by powder X‐ray diffraction (PXRD) and their crystallographic unit cell structure is refined by single crystal X‐ray diffraction (SCXRD) analyses. The thermal stability of the grown polymorphs is judged through differential scanning calorimetry (DSC). Results suggest that the supersaturation plays a key role in the nucleation and growth behaviour of the stable and metastable polymorphs of L‐histidine in aqueous solution.