Abstract
Polymorphs have a tendency to undergo solution-mediated transformation from one form to another during crystallization. Various in situ techniques explored for understanding the crystallization process include, Raman spectroscopy, near-infrared spectroscopy (NIR), and focused beam reflectance measurement (FBRM). Both Raman and NIR techniques are used for polymorphic identification. FBRM has gained much popularity as an ideal technique for studying and improving particle size. The crystallization process can be improved using FBRM by studying the meta-stable zone, temperature of crystallization, and primary and secondary nucleation. This FBRM technique offers a quick and time-saving approach along with insight on the particle size of the product. The same technique can be used during scale up to understand and monitor crystallization processes. This report describes a different application of FBRM, which involves monitoring the changes in chord length distribution as a result of polymorphic transformation associated with temperature during crystallization. Needle-shaped Form III of acitretin undergoes solvent-mediated transformation to cube-shaped Form II. This polymorphic transformation is monitored by monitoring the chord length distribution.
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