PhD ceremony Mr. T.A. Willemsz: Blending of agglomerates into powders quantification and understanding of mixing mechanisms in dry blending

PhD ceremony: Mr. T.A. Willemsz, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Blending of agglomerates into powders quantification and understanding of mixing mechanisms in dry blending

Promotor(s): prof. K. van der Voort Maarschalk

Faculty: Mathematics and Natural Sciences

Presence of drug agglomerates in a blend poses a potential safety risk in e.g. pharmaceutical applications. Therefore, agglomerates need to be removed. The objective of the thesis of Tofan Willemsz is to identify the basic mechanisms of agglomerate breakage during powder blending. This mechanism is the basis to assess the critical process parameters and rules scale-up of the mixing process.

Experiments using so-called brittle Calibrated Test Particles provided evidence that agglomerates reduce in size via an abrasion mechanism. This made it possible to introduce a mechanistic description to quantify abrasion rates during dry powder blending. The abrasion rate is not only influenced by the (mechanical) properties of agglomerates and process conditions, but also by the particle size distribution of the filler.

Applying a novel method to measure powder velocities made it possible to develop a quantitative model that describes the relationships between powder motion during blending and agglomerate abrasion. A Stokes number (St_Abr ) defined as the ratio between the kinetic energy density of the bed and the work of fracture of agglomerates predicts the rate of agglomerate abrasion very well. The conclusion is that particle velocity critically affects agglomerate abrasion and with that mixing time.
The St_Abr approach demonstrates to be a useful tool to predict agglomerate abrasion rate during blending in a tumbling blender and when technology is transferred between different high-shear mixer scales/types. In addition, applying the St_Abr approach revealed a transition point that in both cases is determined by the fill-volume.