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Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant

By Johannes Khinast1; Martin Horn2; Jakob Rehrl3; Selma Celikovic4; Johannes Poms3

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

View Link (HTM)

Category

Peer-reviewed journal

Published on CMKC

Abstract

ConsiGmaTM-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw granulation affect the quality of intermediate and final products. This paper proposes methods for real-time monitoring of these quantities and control-oriented modeling of the granulator.

The PSD of wet granules is monitored via an in-line process analytical technology (PAT) probe based on the spatial velocimetry principle. The algorithm for signal processing and evaluation of PSD characteristics is developed and applied to the acquired PSD data. A dynamic process model predicting PSD characteristics from granulation parameters is trained via the local linear model tree (LoLiMoT) approach. The experimental data required for the model training are collected via systematically designed excitation runs. Finally, the performance of the identified model is examined and verified by means of a new set of validation runs. Furthermore, an in-line PAT probe based on Raman spectroscopy is developed and integrated after the granulator. The API- and liquid content of produced wet granules are evaluated from the spectral data by means of chemometric modeling, and chemometric models are validated on a separate set of experimental data. The solutions proposed in this research can be used as a reliable (and necessary) basis for the development of advanced quality-by-design control concepts (e.g., PSD process control). Such concepts would ultimately improve the ConsiGmaTM-25 process performance in terms of robustness against disturbances and quality of intermediate and final products.

Journal

International Journal of Pharmaceutics

DOI

10.1016/j.ijpharm.2023.123038

Type of publication

Peer-reviewed journal

Affiliations

  • Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13/2, 8010 Graz, Austria
  • Institute of Automation and Control, Graz University of Technology, Inffeldgasse 21b, 8010 Graz, Austria
  • Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/III, 8010 Graz, Austria

Article Classification

Research article

Classification Areas

  • Process Modeling
  • Process Analytical Technology

Tags

  1. continuous manufacturing
  2. Control oriented modeling
  3. Data driven process modeling
  4. Local linear model tree (LoLiMoT)
  5. Process analytical technology (PAT)
  6. Twin-screw granulation