Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction/Dry Granulation Based on Laser Diffraction

Abstract

Purpose: Roll compaction/dry granulation is established in manufacturing of solid oral dosage forms and, within the context of continuous manufacturing, it has sparked interest as material is fed, processed, and ejected continuously while also providing large possible throughputs. However, this amount of material has to be adequately controlled in real time to assure quality. Methods: This research aimed at monitoring the critical quality attribute granule size distribution in continuous roll compaction/dry granulation (QbCon®; L.B. Bohle, Ennigerloh, Germany) using in-line and on-line laser diffraction. The influence of varying process parameters and excipient formulations was studied and evaluated with the prospect of using this technique to develop control loops. For this purpose, residence time parameters were assessed. In- and on-line data was compared with off-line laser diffraction and dynamic image analysis data. Results: The system successfully monitored the granule size distribution in a variety of process parameters and throughputs (up to 27.5 kg/h). It was sensitive to changes in process parameters and changes in material blends, which could pose a potential threat to the final drug products’ quality. Average event propagation time from the compaction zone to the laser diffraction system of 17.7 s demonstrates the systems’ fast reaction time. Conclusion: Results highlight laser diffraction as a valuable method of in- and on-line size determination and allow for the development of a control strategy using this principle.