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Development and Application of Control Concepts for Twin-Screw Wet Granulation in the ConsiGmaTM-25: Part 2 Granule Size

By Selma Celikovic1; Johannes Poms2; Johannes Khinast3; Martin Horn4; Jakob Rehrl2

1. Research Center Pharmaceutical Engineering GmbH, Institute of Automation and Control, Graz University of Technology 2. Research Center Pharmaceutical Engineering GmbH 3. Research Center Pharmaceutical Engineering GmbH, Institute of Process and Particle Engineering, Graz University of Technology 4. Institute of Automation and Control, Graz University of Technology

Published on CMKC

Abstract

Traditional operation modes, such as running the production processes at constant process settings or within a narrow design space, do not fully exploit the advantages of continuous pharmaceutical manufacturing. Integrating Quality by Control (QbC) algorithms as a standard component of production processes can mitigate the effect of diverse process disturbances and enhance process efficiency, particularly in terms of production costs and environmental footprint. This paper explores the potential of QbC algorithms for optimizing twin-screw wet granulation in the ConsiGmaTM-25 manufacturing line, specifically addressing granule size. It represents the second part of a study (Celikovic et al. (2024)) focused on granule composition.

The concepts proposed in this work rely on process analytical technology (PAT) equipment for real-time monitoring of the granulation CQAs and a dynamic process model linking the granulation process parameters and the monitored CQAs. The granule size model identified via the local-linear-model-tree (LoLiMoT) algorithm is used to develop both a model predictive controller (MPC) and a granule size soft sensor. The MPC employs this model as a core component for selecting optimal granulation parameters to ensure the production of granules with target size. A digital operator assistant is developed to address disturbances that cannot be mitigated via MPC but can be eliminated by the plant operators.

This study systematically outlines a workflow, starting from conceptualization, moving through simulation development, and finally ending with real-world application on a production line. In this final step, all proposed concepts are transferred to the ConsiGmaTM-25 manufacturing line, where their performance is validated through selected disturbance scenarios.

Journal

International Journal of Pharmaceutics

DOI

10.1016/j.ijpharm.2024.124125

Type of publication

Peer-reviewed journal

Affiliations

  • Research Center Pharmaceutical Engineering GmbH
  • Institute of Automation and Control, Graz University of Technology
  • Institute of Process and Particle Engineering, Graz University of Technology

Article Classification

Research article

Classification Areas

  • Process Analytical Technology
  • Process Control
  • Process Modeling

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