On the modelling of granule size distributions in twin-screw wet granulation: Calibration of a novel compartmental population balance model

Abstract

Abstract In recent years, novel developments in the continuous manufacturing of solid dosage forms using twin-screw wet granulation have grasped the attention of the pharmaceutical industry. In spite of this progress, there still exists a lack of fundamental knowledge on the physical processes occurring in the barrel of the twin-screw granulator. A major contributor to this knowledge gap has been the unavailability of measurements of granule properties (particle size, liquid content, porosity, etcetera) along the length of the barrel. Recently conducted tedious measurements at different barrel locations have been essential to build a hypothesis in terms of locally occurring mechanisms in twin-screw wet granulation. This paper proposes a novel kernel for modelling either the uni- or bimodal behaviour observed at different L/S ratios in the wetting zone, assuming pure aggregation only. Furthermore, a two stage (wetting and kneading zone) compartmental population balance model is constructed to successfully simulate granule sizes from preblend to the end of the granulator. This population balance model can simulate granule size distributions at a reasonable accuracy both in the case of single compartments as well as in the full two stage compartmental set-up. The proposed model in this paper is a first important step in knowledge build-up of twin-screw granulation and towards a general population balance model for twin-screw wet granulation.