Antisolvent precipitation of PDI 747: Kinetics of particle formation and growth

The application of two recently developed protocols for the fast and robust determination of nucleation and growth kinetics to the antisolvent precipitation of PDI 747 is presented in this work. Both characterization methods are based on two in situ process analytical technologies, i.e., attentuated total reflection-Fourier transform infrared spectroscopy and focused beam reflectance measurement, to monitor the liquid and the solid phase during the characterization experiments. The method to determine growth rate kinetics is based on seeded batch desupersaturation experiments. It combines the accurate characterization of seed particle size distributions and the measurement of desupersaturation profiles for different experimental conditions with population balance modeling and an optimization routine to determine the growth mechanism and the kinetic parameters. In a second step, the growth kinetics are combined with induction time experiments to calculate the nucleation rate. Earlier, these protocols were successfully applied to a-L-glutamic acid, consisting of prismatic crystals. In the case of PDI 747, their application is a challenge due to the needle-like shape of the crystals. The benefits and the limitations of the proposed method are thoroughly assessed.