Model development and calibration of two-dimensional population balance model for twin-screw wet granulation based on particle size distribution and porosity

Abstract

Population balance models (PBMs) have been widely studied for the simulation of continuous twin-screw wet granulation. Due to the limited data availability and computational efforts, one-dimensional PBM is the most popular application to the pharmaceutical industry. While multi-dimensional PBMs can predict multiple granule quality attributes, model development and calibration has been the big challenges. This paper presents a two-dimensional compartmental PBM which compute granule size and porosity. Granulation experiments were performed for two formulations and two process settings, followed by granule characterizations. In PBM development, consolidation was newly introduced, whereas the aggregation and breakage kernels were based on the previous model. Calibration results proved that the model can simulate granule size and porosity simultaneously for different formulations and process settings. Some cases show porosity increase that needs to be considered in the future. Further experiments and model development can increase the applicability of the two-dimensional PBM for the pharmaceutical industry.