In-line Monitoring of Granule Moisture and Temperature throughout the entire Fluidized-bed Granulation Process using Microwave Resonance Technology
Part I
Caroline Buschmüller1,2, Wolfgang Wiedey2, Claas Döscher3, Matthias Plitzko4, Jörg Breitkreutz1 1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf (Germany)
2 Nextpharma PHARBIL Waltrop GmbH, Waltrop (Germany)
3 Advanced Microwave Systems GmbH, Hamburg (Germany)
4 Glatt GmbH, Binzen (Germany) Corresponding author: Prof. Jörg Breitkreutz, Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf (Germany); e-mail: joerg.breitkreutz@uni-duesseldorf.de
The authors report on the implementation and validation of a novel sensor system based on microwave resonance technology (MRT) with frequency shift and damping used for the inline control of complete granulation processes with moisture contents ≤ 7.5 % in fluidized-bed apparatus. The sensor most recently introduced for the end-point determination of drying processes also enables the in-line moisture determination of solids and simultaneously the measurement of powder density and temperature. The adjustment and calibration of the sensor system for determination of the residual granule water content was successfully performed for five consecutive batches using two reference methods, Karl Fischer titration and the determination of the loss on drying induced by infrared light exposure. The MRT sensor was equivalent to the reference methods concerning the granule moisture determination, but delivers continuous values instead of discontinuous data. Other recorded parameters like the product temperature measured at the sensor’s surface facilitate the full understanding and the rational steering of the granulation process.
Furthermore, it was possible to demonstrate within an experimental set-up that the in-line monitoring of the granule moisture using the novel sensor system enables the detection of a deviating process course and therefore allows the intervention at an early stage. The novel MRT sensor system is a valuable tool for the in-line monitoring of the granulation process in pharmaceutical processing. Microwave resonance technology exhibits multiple opportunities to meet FDA’s PAT approach. Key words Fluidized-bed granulation • Granule water content • In-line-Monitoring • Microwave resonance technology • Moisture determination • Process analytical technology (PAT) |
