Realistic process simulator for control strategy evaluation in continuous direct compaction tablet manufacturing

This study introduces a mechanistic, high-fidelity simulation environment for continuous direct compaction (CDC) tablet manufacturing, integrating feeders, blender, hopper, and tablet press models into a unified framework. The platform realistically captures material flow dynamics, residence time effects, and multivariable interactions, providing a robust virtual environment for in silico control design and testing. A disturbance-aware feedforward-feedback control architecture is evaluated across realistic scenarios, including upstream flowrate and concentration disturbances, raw material variability (±10-20% bulk density changes), and model-plant mismatch. Results demonstrate the platform's capability to systematically assess control performance and robustness, supporting safe optimization of manufacturing processes. This work lays the foundation for scalable, model-informed control development and de-risking of future plant-wide control strategies, aligning with the Pharma 4.0 vision of predictive and adaptive continuous pharmaceutical manufacturing.