Combination of a rotating tube sample divider and dynamic image analysis for continuous on-line determination of granule size distribution.
The granule size distribution is a critical quality attribute of granules. It has a great impact on further packaging or processing. Due to increasing interest in continuous manufacturing techniques, it is of high interest to develop an in-line or on-line tool to monitor the granule size distribution. However, development of an in-line measurement tool for granule size distribution was challenging since large throughput and inhomogeneous product stream are limiting factors for current particle size analyzers. In this study, continuous sampling was tested in conjunction to a continuous on-line method of size determination using dynamic image analysis. A rotating tube sample divider was used to split previously compacted material in representative samples at different ratios and the sample was directly conveyed to the particle size analyzer where the granule size distribution was determined. The method was tested for different granule sizes to determine limits of detection and its ability to detect these changes immediately, as this enables real-time monitoring of the process. This research is the base for development of control tools concerning the granule size distributions for continuous granulation processes.
['Wilms|Annika|A|', 'Knop|Klaus|K|', 'Kleinebudde|Peter|P|']
Dynamic image analysis Granule size distribution Continuous manufacturing Representative sampling CM, continuous manufacturing CQA, critical quality attributes DIA, dynamic image analysis FDA, U.S. Food and Drug Administration GSD, granule size distribution PAT, process analytical technologies Process analytical technologies Process monitoring Q3, volume-based cumulative undersized curve RCDG, roll compaction/dry granulation SY, symmetry factor TSG, Twin Screw granulation