Critical insights into real-time granule size characterisation during segmented fluid-bed drying as part of a continuous ConsiGma™25 system

This study demonstrates the implementation of a Parsum real-time granule size monitoring system within the segmented fluid-bed dryer of the ConsiGma™25 continuous manufacturing line. Reference real-time patterns were established for granules produced at liquid-to-solid (L/S) ratios of 0.15, 0.3 and 0.4, developing a comprehensive understanding of granule size throughout the entire drying process. The in-line measurements were found to be influenced not only by the size of individual granules passing through probe's optics, but also by granules' movement as a population during the process. It was also highlighted that the filling phase causes erratic granule movement, which further affects the real-time characterisation. Increasing the L/S ratio resulted in the formation of larger granules and a significant reduction in granule detection rate – from a maximum of 2500 granules/s at L/S 0.15 to 270 granules/s at L/S 0.4 – while the moisture content post-drying ranged from 2.4 % to 10.8 %. Granules formed under the highest L/S ratio also imposed processing and measurement limitations due to extensive liquid bridge formation, ultimately leading to channelling. Furthermore, off-line validation confirmed that overlapping granules distort Parsum size estimations, particularly causing overestimations of the Dv90 percentile by up to 13.97 %. Lastly, to support real-time decision making and ensure compliance with regulatory guidelines for continuous manufacturing regarding determination of any irregularities during processing, intentional process disturbances were created. By varying the L/S ratio from 0.15 to 0.4 during operation, size deviations from reference trends were detected and characterised in-line, enabling detection of process deviations using sensory measurement techniques.