In-line Raman-based quantification of the anhydrous content in a fully integrated continuous powder-to-granule line

This research is based on a fully integrated continuous twin-screw wet granulation line from powder feeding to dried granules. One of its crucial steps is continuous drying, which can influence the crystal form and thus, the quality of the granules. Therefore, the main objective of this research was to develop a Raman spectroscopic method for monitoring the crystal form transition in-line and real-time during the continuous process while applying different drying temperatures. Dextrose was used as a model material due to its high industrial relevance as an active pharmaceutical ingredient and excipient. The real-time monitoring of the granules' crystal form demonstrated that drying at higher temperatures (100 °C and 120 °C) resulted in partial dehydration of the initial α-d-glucose monohydrate. Raman spectroscopy combined with multivariate data analysis proved suitable for real-time quantification of anhydrous content with a root mean square error of 3.3 % w/w. The results were validated by various conventional, off-line analytical techniques, which further confirmed the reliability of the model and the detected anhydrous content. This work shows the high predictive performance of Raman spectroscopy for in-line and real-time anhydrous content monitoring in a fully integrated continuous powder-to-granule line, enhancing process understanding and ensuring high and consistent product quality.