Using MC plots for control of paracetamol crystallization

•Application of process analytical technology.•Correlation of online measurements to the mean crystal size.•Utilization of feedback to control the mean crystal size.

We apply the mass-count framework to understand and control batch cooling crystallization of paracetamol from ethanol. The aim is twofold: (1) to examine the crystallization/dissolution dynamics for this commonly studied system from the mass-count perspective and (2) to test the generality of the framework for establishing crystal size control. Toward the first aim, we gathered experimental results that reveal the dynamics of paracetamol crystallization and dissolution under different temperature profiles. In most situations, the observed dynamics align with expectations and can be interpreted as straightforward crystallization or dissolution. In some cases, however, the experimental results show dynamics that are complex and do not find clear mechanistic interpretation. Nevertheless, in gathering the experimental results we can characterize the dynamics directly in terms of the expected movement in MC space. Such a characterization is useful for establishing control. Toward the second aim, we employed the mass-count framework to develop feedback policies for controlling the mean crystal size. Here we find that, despite the noted complexities, the general control methodology is flexible. Experimental results confirm control over the mean crystal size for three test runs.