PROJECT AIM
Wet Granulation is a size enlargement process to form granules with controlled properties by addition of a liquid binder. This is mainly done to improve the flowability of the powder. Earlier industrial approaches of wet granulation have mainly been done by batch processing (rotating drums, tumblers) on a basis of quality by testing. Recently, especially in the pharmaceutical and biopharmaceutical sector, a growing interest to improve the manufacturing sites has changed the paradigms to a Quality by Design thinking. Differing from the Quality by Testing approach, in Quality by Design the understanding of underlying process mechanisms is of great importance to develop continuous processes (twin-screw, fluidized bed, extrusion) with increased output, consistent quality and reduced operator involvement. No comprehensive model exists to predict this process yet, and the screw has to be empirically adjusted to achieve a homogeneous size distribution. A computer model that can predict the dispersion and growth of the particle size in terms of screw shape, particle and fluid properties will shorten the optimization effort, and lead to more efficient screw designs.
PROJECT DESCRIPTION
A multidimensional macro-model will be used to resolve the domain in time and flow direction. Population Balance Models (PBM) are used to capture the wetting and aggregation as well as breaking and consolidation effects, by applying appropriate rate kernels to model the process on a macroscale
Calibration and validation of a multidimensional PBM from experiments is not straightforward. Thus, a calibratable DPM model for the microscopic scale will also be developed to determine closure relations for the macro model (collision rates, breakage probabilities, etc). Because our parameter space is likely high-dimensional, a heterogenous multiscale approach (Fig. 1) will be employed. Furthermore Coarse-Graining will be used to extract continuum fields from the calibrated microscale model
Figure 1: HMM coupling of a 1D macroscopic model to a database of microscale simulation results.
Early on, experiments will be performed adopting rapid prototyping to build a twin-screw granulator setup. An innovative design (Fig. 2) will be applied to keep the experiments as simple and as flexible as necessary for the investigation of the process. In This way our experimental setup will be able to calibrate and validate our microscale simulations, transitioning from rapid to virtual prototyping.
Figure 2: Simple and innovative experimental design for the investigation of a twin-screw wet granulator