title: Implementation of an advanced hybrid MPC-PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plant.
abstract: 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.
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: ravendra.singh@rutgers.edu.
authors: Ravendra
authors: R
authors: Singh
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Abhishek
authors: A
authors: Sahay
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Krizia M
authors: KM
authors: Karry
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Fernando
authors: F
authors: Muzzio
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Marianthi
authors: M
authors: Ierapetritou
authors: Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: rohit.r@rutgers.edu.
authors: Rohit
authors: R
authors: Ramachandran
mesh_terms: D009862:Online Systems; D025341:Principal Component Analysis; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D013607:Tablets
keywords: Continuous processing; Hybrid; Model predictive control; NIR; PCA; Pharmaceutical