Continuous Twin-Screw wet granulation process with In-Barrel drying and NIR setup for Real-Time Moisture Monitoring

[Display omitted] •Single unit operation wet granulation and drying by utilizing in-barrel drying during twin screw wet granulation at pilot scale.•Reduce manufacturing footprint, time, and environmental exposures while also presenting a truly continuous drying process to pair with continuous twin-screw wet granulation.•Screw configuration, vacuum and position, degree of fill, and surface area under vents most impactful factors to achieve single unit operation in-barrel drying during twin screw wet granulation.•Real-time NIR monitoring of residual moisture to expedite development time and minimize material waste during twin screw wet granulation. The purpose of this study was to evaluate if wet granule formation and drying could take place in a single operation by utilizing in-barrel drying. The drying kinetics of the formulation were studied in order to select appropriate processing parameters and assess feasibility with short residence times in the extruder. The 18-mm extruder was operated in a 40:1 L:D ratio with 8 zones. The first two zones were used for material feeding and wet granule formation and the remaining zones were used for drying at elevated temperature. The impact of screw configuration as well as screw speed, feed rate, and residence time were all studied to optimize the drying process. Due to limitations of temperature and residence time, vacuum was added to enable sufficient drying. In-line NIR spectroscopy was incorporated into the twin-screw wet granulation (TSWG) process to monitor the moisture content of wet granules in real-time. The set-up was optimized and a predictive model was developed for future experiments. This study demonstrated the success of this technique on a pilot-scale (18-mm) extruder for the first time. Granules were formed and dried to a target loss on drying (LOD) of less than 2 % at moderate temperatures (100 °C – 110 °C) with one single operation. Streamlining wet granulation and drying into one unit operation can have a profound impact on pharmaceutical manufacturing reducing time, footprint, and environmental exposure due to reduced product transfers.