title: An engineering study on the enhanced control and operation of continuous manufacturing of pharmaceutical tablets via roller compaction.
abstract: A novel manufacturing strategy based on continuous processing integrated with online monitoring tools coupled with efficient automatic feedback control system is highly desired for efficient Quality by Design (QbD) based manufacturing of the next generation of pharmaceutical products with optimal consumption of time, space and resources. In this manuscript, an efficient plant-wide control strategy for an integrated continuous pharmaceutical tablet manufacturing process via roller compaction has been designed in silico. The designed control system consists of five cascade control loops and three single control loops resulting in 42 controller tuning parameters. An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been proposed and the designed control system has been implemented in a first principle model-based flowsheet that was simulated in gPROMS (Process System Enterprise). The advanced techniques (e.g. anti-windup) have been employed to improve the performance of the control system. The ability of the control system to reject the unknown disturbances as well as to track the set point has been analyzed. Results demonstrated enhanced performance of critical quality attributes (CQAs) under closed-loop control compared to open-loop operation thus illustrating the potential of closed-loop feedback control in improving pharmaceutical manufacturing operations.
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems, Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ravendra
authors.initials: R
authors.lastname: Singh
authors.forename: Marianthi
authors.initials: M
authors.lastname: Ierapetritou
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
mesh_terms: D003198:Computer Simulation; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011786:Quality Control; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets