title: In-line monitoring of particle size in a fluid bed granulator: investigations concerning positioning and configuration of the sensor.
abstract: According to the ICH Q8 guideline, analytic technologies (PAT) are important tools for characterization and optimization of pharmaceutical manufacturing processes. Particle size as a critical quality attribute for granules is therefore an important parameter that should be monitored during the fluid bed granulation process. This work focusses on optimizing position and configuration of an SFT-sensor for the in-line measurement of particle size distribution in a Glatt GPCG 3 fluid bed granulator. As model-substances, different grades of microcrystalline cellulose were used. The in-line measured particle size and particle rate in the sensor were evaluated. A sensor position in the deceleration zone of the granulator was found to be promising for in-line particle size measurement. Most reliable data were generated in this position when the probe was placed in a distance of 11cm from the chamber wall to avoid bias by the inlet air stream. No major influence of rotation angle of the probe was found in this position. Furthermore, an entire fluid bed granulation process was successfully monitored with the sensor installed in the optimized setting.
authors.affiliation: Jenapharm GmbH & Co. KG, Otto-Schott-Str. 15, 07745 Jena, Germany; University of Leipzig, Institute of Pharmacy, Eilenburger Str. 15A, 04317 Leipzig, Germany. Electronic address: Katrin.rossteuscher@gmx.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Roßteuscher-Carl
authors.affiliation: Jenapharm GmbH & Co. KG, Otto-Schott-Str. 15, 07745 Jena, Germany. Electronic address: fricke1sabine@gmx.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fricke
authors.affiliation: University of Leipzig, Institute of Pharmacy, Eilenburger Str. 15A, 04317 Leipzig, Germany. Electronic address: mhacker@uni-leipzig.de.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hacker
authors.affiliation: University of Leipzig, Institute of Pharmacy, Eilenburger Str. 15A, 04317 Leipzig, Germany. Electronic address: schulz@uni-leipzig.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schulz-Siegmund
mesh_terms: D002482:Cellulose / Q000737:chemistry; D007834:Lasers; D009862:Online Systems; D010316:Particle Size; D012542:Scattering, Radiation; D013678:Technology, Pharmaceutical / Q000295:instrumentation*
chemical_list: D002482:Cellulose; C109691:microcrystalline cellulose
keywords: Fluid bed granulation; Glatt GPCG 3.1; In-line particle size measurement; Microcrystalline cellulose; Process analytical technologies; Spatial filtering technology