Characterization and scale-up of ultrasound reactors for flow crystallization, emulsification and encapsulation.

The goal of this PhD research is to control and improve particles properties and flowability of active pharmaceutical ingredients (API’s) by continuous spherical agglomeration (SA) in combination with ultrasound assisted nucleation. Spherical agglomeration involves the addition of a bridging liquid in the wetting phase to form agglomerates which are shaped during the subsequent growth phase. Sononucleation enables control over the initial size and amount of the formed particles whereas the use of a continuous flow reactor separates nucleation, wetting and growth phase. With this approach, the project aims to identify the mechanism responsible for wetting, to investigate the effect of process parameters and crystal properties on wetting and to investigate the effect of pulsation on shaping and agglomeration during the growth phase. The project starts by investigating the correlation between flowability data and inline microscopy and image analysis data. Relevant particle properties are identified to determine a model to predict flowability based on inline images. Experiments in a sonicated PFR are carried out using image analysis tools and high speed camera to visualize occurring mechanism and to investigate the effect of process parameters as crystal size, crystal shape, amount of crystals, bridging liquid droplet size and pulsation settings in both wetting and growth phase.