Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes

  • Ravendra SinghEmail author
  • Carlos Velazquez
  • Abhishek Sahay
  • Krizia M. Karry
  • Fernando J. Muzzio
  • Marianthi G. Ierapetritou
  • Rohit Ramachandran
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


A novel manufacturing strategy based on continuous processing, integrated with online/inline monitoring tools, coupled with an advanced 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 work, an advanced hybrid MPC-PID control system as well as a simpler PID controller for a direct compaction continuous tablet manufacturing process has been designed and implemented for a pilot-scale pharmaceutical process. An NIR sensor, an online NIR prediction tool, a PAT data management tool, an OPC communication protocol, a standard control platform and control hardware have been used to close the control loop. A systematic methodology to design and implement the control system has been also proposed. A control framework with features such as the option to run the plant in open-loop as well as in a closed-loop scenario has been developed. Furthermore, within the closed-loop scenario, options for a simpler PID, a dead time compensator (Smith predictor) as well as an advanced model predictive controller have been included. The feature to run the control strategy in simulation mode has been added to the control platform to facilitate virtual control system design and performance evaluation. Two case studies involving a direct compaction continuous tablet manufacturing process have been considered to demonstrate the closed-loop operation. Case Study 1 was completed at Rutgers University and constituted the use of a continuous cylindrical blender with a rotating screw. Case Study 2 was based on a continuous tumble mixer and was completed at the University of Puerto Rico—Mayaguez Campus (UPRM).

Key words

Control system Model predictive control Pharmaceutical Continuous Tablet manufacturing 



This work is supported by the National Science Foundation Engineering Research Center on Structured Organic Particulate Systems (ERC-SOPS) through Grant NSF-ECC 0540855. The authors would also like to acknowledge Paul Brodbeck (CAI) and Rodolfo J. Romañach (UPRM) for their meaningful discussions.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ravendra Singh
    • 1
    Email author
  • Carlos Velazquez
    • 2
  • Abhishek Sahay
    • 1
  • Krizia M. Karry
    • 1
  • Fernando J. Muzzio
    • 1
  • Marianthi G. Ierapetritou
    • 1
  • Rohit Ramachandran
    • 1
  1. 1.Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical and Biochemical EngineeringRutgers, The State University of New JerseyPiscatawayUSA
  2. 2.Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Department of Chemical EngineeringUniversity of Puerto Rico MayaguezMayaguezUSA

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