(120a) A Combined Experimental and Model-Based Approach to Prediction of Particle Size Attrition In Agitated Dryers

The final crystallization of an active pharmaceutical ingredient often requires meeting a

target particle size specification in order to facilitate downstream processing of the

material in formulation of the final dosage form. Agitated filter dryers, often used to

prevent exposure of operations personnel to hazardous compounds, can alter the particle

size produced from the crystallization. During filtration and drying, agitation can result

in particle size attrition due to breakage of the particles or agglomeration of the particles

into undesired lumps. In order to successfully scale up processes from small to large

filter dryers while minimizing particle attrition and agglomeration, the mixing in filter

dryers must be understood. Discrete Element Model (DEM) simulations can be used to

characterize the mixing in filter dryers at various different scales and determine the forces

and velocities that the particles experience, which can be linked to particle breakage via

mechanical property assessment of the powder particles. We will report our results on

simulations of mixing in filter dryers, the relation of particle size attrition to the

mechanical properties of the powder particles, and our attempt to predict particle size

attrition using the simulations and understanding of the fundamental mechanical

properties of the API.