Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. III. Wet Milling

Abstract

Several operating and control strategies with the purpose of manipulating the size and shape of crystals exhibiting needle-like morphology are presented using an ex situ wet mill as the actuator. A model-based operating policy and different model-free controllers are discussed. These controllers were coupled with an online particle size and shape monitoring tool. First, the attainable region in the size and shape space for a wet milling operation was evaluated in a simulation framework using a multidimensional population balance model describing the breakage phenomenon. Second, the operating and control strategies were tested experimentally in a lab-scale setup using two different milling configurations and two different compounds, namely, β l-glutamic acid and γ d-mannitol. The goal of the experiments was to drive various seed populations of the two compounds to several target average lengths in the size and shape space. It was observed that the model-based operating policy, run without any feedback action, was not able to achieve this goal for arbitrary seed populations. The model-free controllers incorporating feedback were able to do so without relying on any multidimensional breakage model. These controllers enable the robust operation of wet milling stages in complex crystal size and shape modification processes.