Twin screw extrusion in formulated product manufacturing I – Twin screw granulation

Abstract

Twin screw extrusion (TSE) has established itself as an effective technology for the continuous manufacturing of oral solid dosage forms, owing to its superior mixing efficiency, modular screw design, and precise process control. Its adoption in the pharmaceutical industry has been significantly accelerated by regulatory initiatives, promoting Quality by Design (QbD) and continuous manufacturing. TSE is primarily adopted for two key applications: twin screw granulation (TSG) for agglomerating powders and hot-melt extrusion (HME) for producing amorphous solid dispersions (ASDs) to enhance the bioavailability of poorly water-soluble drugs. This review focuses on TSG aiming to provide a comprehensive and critical evaluation of the application of TSE in granulation, especially on how the complex flow fields, intense shear stresses, and controlled residence times generated within the extruder govern critical quality attributes (CQAs) including granule size, density, porosity, and mechanical strength. The review further discusses emerging trends and future perspectives of TSG, highlighting the advances in mechanistic modelling for accelerated product and process development, as well as the implementation of digital twins for real-time monitoring, predictive process control, and closed-loop manufacturing.