(256a) Comparison of a Powder Mixing Process in Two Different Blenders Using DEM | AIChE

(256a) Comparison of a Powder Mixing Process in Two Different Blenders Using DEM

Authors 

Bohling, P., RCPE Gmbh
Salehi, M., Research Center Pharmaceutical Engineering GmbH
Poms, J., Research Center Pharmaceutical Engineering GmbH
Beretta, M., Research Center Pharmaceutical Engineering Gmbh
Bautista, M., F. Hoffmann-La Roche
Khinast, J. G., Graz University of Technology
Gavi, E., F. Hoffmann - La Roche Ltd
Powder mixing is a critical step in a pharmaceutical continuous or semi-continuous direct compaction process. Providing and maintaining a well-mixed powder is essential for the final product's quality. Especially for formulations containing lubricants like magnesium stearate, it is essential to have a well-defined mixing time as it influences the tensile strength of the tablets. Although powder mixing is often studied extensively experimentally, computational methods can provide more insight and therefore find increasing use. In particular, the discrete element method (DEM) allows for a fundamental mechanistic understanding of the mixing process.

This work uses the discrete element method to investigate and understand mixing in two types of mixers. A high-shear mini-batch blender (MBB) is compared to a 2 L Tubular blender. The work presents a comprehensive overview of the influence of the two blender types and process conditions on mixing. In addition, the effect of the powder composition on the mixing behavior is studied using DEM model parameters that depend on the composition. These model parameters are obtained by performing bulk powder characterization, e.g., particle size distribution or FT4 measurements of the used material/powder blend, and adapting the DEM model parameters to fit the experimental results.

To this end, a small experimental design in both blenders is simulated. The simulations are analyzed for their mixing behavior, distance traveled and shear acting on the powder. A model is developed to predict the tablet's tensile strength as a function of the mixing time, and the results are compared with experimental data. These simulation results are analyzed to quantify mixing in the MBB utilizing blend uniformity.

This work comprehensively overviews the comparability and scalability of the two discussed blender types. A scaling strategy between both blenders is discussed and evaluated for the development of a continuous production process.