(162a) A Compartmentalized, Numerical Model of Continuous Blending

Authors: 
Bunchatheeravate, P., Vertex Pharmaceuticals
Bullard, J. W., Vertex Pharmaceuticals
Dale, S., Vertex Pharmaceuticals
Connelly, G., Vertex Pharmaceuticals
O'Mahony, M., Vertex Pharmaceuticals
Here we present an empirically-derived, numerical model of a continuous blender capable of describing both the mass flow rate and residence time distribution of a given powder as a function of processing conditions. The approach discretizes the blending process in both time and space, describing a stepwise progression of powder through segmented portions of the equipment, which are defined primarily by the geometry of the mixing blades. The model defines three distinct blending regimes within the process: A conveying mode, where powder is rapidly transported from the blender inlet to outlet; a mixing mode, where intermixing of powder between nearby blender segments is more completely described; and a transition regime between the two. Further, we show that coupling the model with a given materials system on a specific blender provides an approach to identifying appropriate process ranges in the context of desired blending regimes. Moreover, the model is shown to serve as a useful analytical tool for defining design spaces in the context of QbD, affording greater mechanistic insights into blending behavior than a standard linear regression analysis of an orthogonal design of experiments.