Inline Monitoring of Taltirelin Crystallization in Batch Cooling Mode Using Raman Spectroscopy

The polymorphic formation of taltirelin (TTL) was monitored inline by Raman spectroscopy in batch cooling crystallization. The concentrations of the polymorphic forms and supersaturation were measured during crystallization and transformation processes. Polymorphic transformation was detected by monitoring the Raman spectra of the two polymorphs in slurry state. The effect of cooling rate and concentration on the polymorphic crystallization was assessed. At a slow cooling rate and a low concentration, the stable form, i.e., the β-form, was nucleated directly without transformation from the α-form. The nucleation mechanism of the two TTL polymorphs was studied using the supersaturation profile tracked by Raman spectroscopy.