Combined Temperature-Moisture Gray-Box Model for Horizontal Fluidized Bed Drying of Pharmaceutical Granules

IFAC-PapersOnLine, vol. 59, pp. 1089–1094

Abstract

Twin-screw wet granulation (TSG) enables continuous particle size enlargement in the manufacturing of solid dosage form pharmaceutics. After wet granulation, a drying step is required, which is realized in the vibrated fluidized bed dryer (VFBD) of the QbCon® 1 lab scale continuous production line. The product’s moisture content and temperature are the critical quality attributes (CQAs) of the drying process. This paper presents an extension for granule temperature to the moisture content model proposed by Elkhashap et al. (2020b). The combined granule temperature and moisture content model can predict both CQAs and gives a physical, quantitative relation between the two values. A full factorial experimental design, varying drying air temperature, air flow, and vibration acceleration was performed on the real VFBD to validate the model. The model shows an accurate prediction for the temperature (RMSE = 4.4K) and for the moisture content (RMSE = 0.021) even with limited amounts of training data present. The model can be used in future work for process optimization, monitoring, and control.

Authors 7

1. Stefan Ruben Tölle corresponding Aachen Institute of Automatic Control (IRT)

   RWTH Aachen University

   Affiliation as printed

   Institute of Automatic Control, RWTH Aachen University, Aachen, Germany

2. Stefan Klinken

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany

3. Ahmed Elkhashap Aachen Institute of Automatic Control (IRT)

   RWTH Aachen University

   Affiliation as printed

   Institute of Automatic Control, RWTH Aachen University, Aachen, Germany

4. Alana Delvos

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany

5. Jörg Breitkreutz

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany

6. Heike Vallery Aachen Institute of Automatic Control (IRT)

   RWTH Aachen University

   Affiliation as printed

   Institute of Automatic Control, RWTH Aachen University, Aachen, Germany

7. Sebastian Stemmler Aachen Institute of Automatic Control (IRT)

   RWTH Aachen University

   Affiliation as printed

   Institute of Automatic Control, RWTH Aachen University, Aachen, Germany