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Combined feedforward/feedback control of an integrated continuous granulation process

By Pereira, Glinka Cathy; Muddu, Shashank Venkat Román-Ospino, Andrés David Clancy, Don Igne, Benoit Airiau, Christian Muzzio, Fernando J Ierapetritou, Marianthi Ramachandran, Rohit; Singh, Ravendra

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Abstract

Continuous manufacturing offers shorter processing times and increased product quality assurance, among several other advantages. This makes it an ever-growing interest among pharmaceutical companies. A suitable efficient control system is however desired for continuous pharmaceutical manufacturing to achieve a consistent predefined end product quality.Continuous manufacturing offers shorter processing times and increased product quality assurance, among several other advantages. This makes it an ever-growing interest among pharmaceutical companies. A suitable efficient control system is however desired for continuous pharmaceutical manufacturing to achieve a consistent predefined end product quality.Methods:In order to control product quality more accurately, the effects of input disturbances need to be proactively mitigated. Therefore, it is desired that a combined feedforward/feedback control system integrated with suitable process analytical technology (PAT) be implemented over a traditional feedback-only control system. The feedforward controller measures and takes corrective actions for disturbances proactively before they affect the process and thereby product quality. The feedback controller considers the real-time deviation of control variable from a pre-specified set point and keeps it at a minimum possible value. The deviation of a control variable from the set point could be due to both measurable and unmeasurable disturbances.ResultsIn this work, a combined control strategy has been developed for a continuous twin screw wet granulation (WG) process. An integrated flowsheet model was developed and simulated in order to evaluate the effect of control loops on critical quality attributes (CQAs). Different strategies of manipulation were evaluated and the best strategy was identified.ConclusionsIn silico study on the combined feedforward/feedback control strategy and feedback-only control strategy demonstrates that the combined loop results in diminished variability of the CQAs.

Journal

Journal of Pharmaceutical Innovation. Volume 14, 2019, 259–285

DOI

10.1007/s12247-018-9347-8

Type of publication

Peer-reviewed journal

Affiliations

  • Rutgers, The State University of New Jersey

Article Classification

Research article

Classification Areas

  • Oral doses
  • Modeling

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