Scale-up of Crystallisation

Crystallisation is a process which is routinely used in the production of pharmaceuticals. Due to the complexity of the process, scale-up can affect key properties of product quality such as particle size distribution (PSD), purity and morphology. Such variability can also affect the performance of downstream processes such as filtration and milling.

Electrical Resistance Tomography (ERT) is a relatively new on-line measurement technology that is gaining acceptance as a means of process monitoring by measuring electrical impedance distribution within a volume. ERT has been widely applied to determine the hydrodynamics and mixing within stirred vessels.

Pharmaceutical development in the laboratory is often performed at near to ‘perfect mixing’ conditions. One of the main challenges with crystallisation scale-up is the increasing importance of mixing during scale-up which has significant impact on crystal quality in terms of PSD.

This white paper will provide experimental results highlighting the link between the hydrodynamics – as characterised through ERT measurements – and mixing within different scales of stirred vessels and the crystal PSD for a model reaction. A comparison between different ERT measurement probe geometries will also be presented.