Model-based characterisation of twin-screw granulation system for continuous solid dosage manufacturing

Abstract

Abstract Continuous twin-screw granulation has received increased attention as it can be embedded in a continuous manufacturing line allowing 24/7 production capacity eliminating scale-up requirements and intermediate storage. The screws have a modular structure (interchangeable transport and kneading discs) allowing greater flexibility in equipment design. However, process knowledge should be further developed both under steady state and dynamic conditions. Mechanistic models incorporating the underlying mechanisms are therefore applied. In this study, the principle constitutive mechanisms such as aggregation and breakage are included in a population balance modelling framework. Based on an experimental inflow granule size distribution and mean residence time of the granulator, predictions of the outflow granule size distribution were made. Experimental data was used for calibrating the model for individual screw modules in the twin- screw granulator. The results showed that the successive kneading blocks lead to a granulation regime-separation inside the twin-screw granulator. The first kneading block after wetting caused an increase in the aggregation rate, which was reduced after the second kneading block. The breakage rate increased successively along the length of the granulator. Such a physical separation between the granulation regimes will be promising for future design and advanced control of the continuous granulation process.