System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction

Ravendra Singh, Marianthi Ierapetritou, Rohit Ramachandran

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables, so that the predefined product quality can be achieved consistently. The direct compaction process considered in this study is highly interactive and involves time delays for a number of process variables due to sensor placements, process equipment dimensions, and the flow characteristics of the solid material. A simple feedback regulatory control system (e.g., PI(D)) by itself may not be sufficient to achieve the tight process control that is mandated by regulatory authorities. The process presented herein comprises of coupled dynamics involving slow and fast responses, indicating the requirement of a hybrid control scheme such as a combined MPC-PID control scheme. In this manuscript, an efficient system-wide hybrid control strategy for an integrated continuous pharmaceutical tablet manufacturing process via direct compaction has been designed. The designed control system is a hybrid scheme of MPC-PID control. An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been used for tuning of both MPC and PID parameters. The designed hybrid control system has been implemented in a first-principles model-based flowsheet that was simulated in gPROMS (Process System Enterprise). Results demonstrate enhanced performance of critical quality attributes (CQAs) under the hybrid control scheme compared to only PID or MPC control schemes, illustrating the potential of a hybrid control scheme in improving pharmaceutical manufacturing operations.

Original languageEnglish (US)
Pages (from-to)1164-1182
Number of pages19
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3 PART B
StatePublished - Nov 2013

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science


  • Continuous processing
  • Hybrid control
  • Model predictive control
  • Pharmaceutical
  • QbD
  • Tablet manufacturing


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