Experimental Characterization and Population Balance Modeling of the Polymorph Transformation of l-Glutamic Acid

In this work, the polymorph transformation of the metastable α to the stable β polymorph of l-glutamic acid at 45 °C was monitored using in situ Raman spectroscopy. In a series of seeded transformation experiments, the effect of different operating conditions on the transformation was studied. Both increasing seed mass and increasing stirring rate decrease the transformation time, thus suggesting an attrition-based secondary nucleation mechanism of the β polymorph. Moreover, it was found that no pure seed crystals of the metastable α polymorph could be produced and that different sieve fractions of the α polymorph contained different amounts of the β polymorph, which was included within the α crystal. These inclusions had a significant effect on the transformation times meaning that in experiments with larger seeds the transformation was faster than in experiments with smaller seeds. Independent seeded batch desupersaturation experiments were conducted to determine the growth rate of the β polymorph. On the basis of this growth rate and of the seeded transformation experiments, the secondary nucleation rate of the β polymorph was estimated using a population balance model. Together with nucleation and growth kinetics of the α polymorph, which were measured previously, a fully descriptive model of the polymorph transformation process was developed.