JOURNAL ARTICLE

Implementation of an advanced hybrid MPC-PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plant

Ravendra Singh, Abhishek Sahay, Krizia M Karry, Fernando Muzzio, Marianthi Ierapetritou, Rohit Ramachandran
International Journal of Pharmaceutics 2014 October 1, 473 (1): 38-54
24974987
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.

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