It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to ensure that the pre-defined end product quality attributes are met in a time and cost efficient manner. In this work, an advanced hybrid MPC–PID control architecture coupled with real time inline/online monitoring tools and principal components analysis (PCA) based additional supervisory control layer has been proposed for a continuous direct compaction tablet manufacturing process. The advantages of both MPC and PID have been utilized in a hybrid scheme. The control hardware and software integration and implementation of the control system has been demonstrated using feeders and blending unit operation of a continuous tablet manufacturing pilot plant and an NIR based PAT tool. The advanced hybrid MPC–PID control scheme leads to enhanced control loop performance of the critical quality attributes in comparison to a regulatory (e.g. PID) control scheme indicating its potential to improve pharmaceutical product quality.

• Rutgers, The State University of New Jersey

• PAT
• Control

1. continuous processing
2. Control
3. Hybrid
4. Model predictive control
5. NIR
6. pat
7. PCA
8. Pharmaceutical
9. Research Article