Accurate in-line sensors that are robust enough to be used in production environment have become available in recent years. This opens up the possibility of using such measurements to control crystallizations interactively in order to improve crystal product consistency. Closed-loop concentration-control (C-control) using Attentuated Total Reflectance – Fourier Transform Infrared (ATR-FTIR) has been the most commonly used feedback control method in which supersaturation is controlled at a constant level. Although C-control has been proven to be robust, a recent study by Chew et al.¹ found that C-control was unable to ensure product consistency in unseeded crystallization systems due to the random nature of primary nucleation.

Focused Beam Reflectance Measurement (FBRM) has emerged as a widely used technique for the in-situ characterization of crystallization systems by monitoring the chord length distributions. It has been used to develop and optimize crystallization processes, track and trouble-shoot crystallizer systems, and to monitor polymorphic forms. Yet, despite the proven useful applicability of FBRM in crystallization, there has not been any published work of automated closed loop strategies using FBRM. In view of the potential difficulty in implementing ATR-FTIR in the production systems due to calibration complexities, it would be advantageous to be able to rely solely on FBRM for reproducibility in product crystals.

In this work, we made use of FBRM in-situ in a feedback loop to improve crystal product quality in a batch crystallizer, without any external loop. The method consists of automated FBRM detection of nucleation, followed by controlled internal seed generation. The technique has been successfully implemented for the cooling crystallization of glycine and paracetamol in water.² Results showed that the crystal product consistency using our technique was comparable to that of externally seeded crystallizations.

1. Chew, J. W.; Black, S. N.; Chow, P. S.; Tan, R. B. H., Comparison between open-loop temperature control and closed-loop supersaturation control for cooling crystallization of glycine. Industrial & Engineering Chemistry Research 2007, 46, (3), 830-838.

2. Chew, J. W. Experimental investigation of the applicability of FBRM in the control of batch cooling crystallization. MEng, National University of Singapore, Singapore, 2006.