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.
Keywords: CM, continuous manufacturing; CQA, critical quality attributes; Continuous manufacturing; DIA, dynamic image analysis; Dynamic image analysis; FDA, U.S. Food and Drug Administration; GSD, granule size distribution; Granule size distribution; PAT, process analytical technologies; Process analytical technologies; Process monitoring; Q3, volume-based cumulative undersized curve; RCDG, roll compaction/dry granulation; Representative sampling; SY, symmetry factor; TSG, Twin Screw granulation.