Polymorphism is a widespread phenomenon in organic compounds and is of crucial importance for chemical and pharmaceutical manufacturing. The purpose of this work was to study the influence of various experimental operating factors on the polymorphic crystallization and solution-mediated transformation processes. These factors included initial concentration of solution, temperature, cooling profile, agitation rate, additive, solvent, seeding etc.

The nucleation, metastability and solution-mediated transformation behavior of model compound (Glycine) have been investigated in detail using various off-line and in-situ monitoring techniques. The polymorphs were characterized by Powder XRD, FTIR, Raman microscope, SEM, as well as TGA and DSC. The crystallization experiments under different operating conditions were carried out in a Mettler Toledo LabMax automatic laboratory reactor system, which was equipped with a Lasentec D600L Focused Beam Reflectance Method (FBRM), a ReactIR and a Kaiser RamanRXN1 analyzer. In-situ transformation observation was also carried out with an optical microscope equipped with a Linkam THMS 600 heating/cooling stage.

On the basis of the in-situ measurements and observations of crystallization and transformation behavior with the variation of operating parameters, the nucleation mechanism of the metastable and stable polymorphs was proposed and discussed. The integration of the different off-line and in-situ analytical measurement techniques greatly assisted to accurately and quantitatively investigate the fundamental phenomena that govern the crystallization and transformation process so as to selectively control the polymorphic crystallization.