(334g) Evaluation of an Industrial Scale Binary Bin Blending Process Using DEM Simulations | AIChE

(334g) Evaluation of an Industrial Scale Binary Bin Blending Process Using DEM Simulations


Benque, B., Research Center Pharmaceutical Engineering
Forgber, T., RCPE
Jajcevic, D., Research Center Pharmaceutical Engineering Gmbh
Doshi, P., Worldwide Research and Development, Pfizer Inc.
Santangelo, M., Worldwide Research and Development, Pfizer Inc^.
Lee, H. G., Worldwide Research and Development, Pfizer Inc.
Gomes Lopes, D., Catalent Pharma Solutions
Schaefer, M., Catalent Pharma Solutions
Khinast, J. G., Graz University of Technology
Bin blending is a unit operation commonly used in oral dosage form manufacturing to mix individual components. It is simple to implement but reaching the desired blend uniformity on an industrial scale can be challenging. One of the main challenges is to obtain the target blend uniformity in a reasonable time frame while avoiding segregation. A suitable blender and operational conditions must be selected considering the material characteristics, batch size, sensitivity to attrition, among other factors.

Several studies have investigated the mixing behavior in various types of blenders on the lab scale. Generally, it was reported that the fill level and the loading pattern have the most significant influence on blending behavior and that differences in particle size, density, or cohesivity between the materials increase the risk of segregation. The segregation patterns in different geometries and under different operational conditions have been reported in the literature. In order to achieve fast and pronounced segregation patterns, most studies have focused on lab-scale blending processes of components with very different properties (such as particle size or density). However, the risk of segregation of realistic pharmaceutical powders with similar properties in an industrial-scale process has not been addressed.

The present work studies the blending of two granular materials in a commercial scale conical-cylindrical geometry using discrete element method (DEM) simulations. The influence of geometrical modifications and operational conditions on the blending behavior and the risk of segregation were evaluated. The influence of asymmetry was studied by implementing mixing elements at the lid. The sensitivity of the process to both the fill level and repeated changes in the rotation direction was investigated.

To that aim, DEM contact model parameters were calibrated for two pharmaceutical granulates based on experimental powder characterization tests. To overcome computational limits, the particle sizes and contact parameters were scaled up while ensuring similar bulk powder behavior. For economic reasons, industrial scale blending processes are often operated at high blender fill levels. The results confirm previous findings which show increased blending times at higher fill levels. To speed up mixing, angled baffles in the lid were found helpful by improving mixing along the rotation axis, but they also increase the risk of axial segregation of the binary blend. It is shown that this enhanced segregation risk, caused by the asymmetry of the mixing elements, can be mitigated by regularly changing the rotation direction of the blender.