Application of a recent FBRM-probe model to quantify preferential crystallization of dl-threonine

The process of preferential crystallization is controlled by crystallization kinetics. Thus a key to run the process satisfactorily is using a process monitoring system eventually combined with a process model. In this context information of the liquid phase composition as well as the time resolved particle size distributions are usually desired. In contrast to measuring the liquid phase composition the inline measurement of particle size distributions is often difficult. The Focused Beam Reflectance Measurement probe (Lasentec, Mettler-Toledo GmbH) is an inline monitoring tool that is capable of measuring so-called chord-length distributions (CLDs). However these CLDs are different to the desired particle size distributions (PSDs). In the presented study this problem is overcome using a recent rigorous mathematical model of the measurement technology to transform PSDs into CLDs. The study shows how the probe model can be adopted to the investigated system using a series of initial validation experiments. Chord-splitting seems to occur when using the Focused Beam Reflectance Measurement probe. A simple modification of the particle geometry is incorporated into the probe model in order to simulate the chord-splitting. The simulated CLDs are then compared to the measured CLDs of different preferential crystallization runs performed for the system d,l-threonine/water. More specifically, measured moments of the chord length distributions along with optical rotation trajectories are compared to calculated moments of a population balance model in order to estimate the kinetic model parameters. This way the presented case study gives a systematic approach on how to apply the used probe model to monitor a preferential crystallization process and parameterize a process model.