Proof of a LOD prediction model with orthogonal PAT methods in continuous wet granulation and drying.

Abstract

Real-time monitoring of critical quality attributes, such as residual water in granules after drying which can be determined through loss-on-drying (LOD), during wet granulation and drying is essential in continuous manufacturing. Near-infrared (NIR) spectroscopy has been widely used as process analytical technology (PAT) for in-line LOD monitoring. This study aims to develop and apply a model for predicting the LOD based on process parameters. Additionally, the efficacy of an orthogonal PAT approach using NIR and mass balance (MB) for a vibrating fluidized bed dryer (VFBD) is demonstrated. An in-house-built, cost-effective NIR sensor was utilized for measurements and exhibited good correlation compared to standard method via infrared drying. The combination of NIR and MB, as independent methods, has demonstrated their applicability. A good correlation, with a Pearson r above 0.99, was observed for LOD up to 16 % (w/w). The use of an orthogonal PAT method mitigated the risk of false process adaption. In some experiments where the NIR sensor might have been covered by powder and therefore did not measure accurately, LOD monitoring via MB remained feasible. The developed model effectively predicted LOD or process parameters, resulting in an R2 of 0.882 and a RMSE of 0.475 between predicted and measured LOD using the standard method.