Oral Formulation Sciences and Technology, Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ 07065, USA.
Oral Formulation Sciences and Technology, Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ 07065, USA.
Int J Pharm. 2023 Jan 5;630:122377. doi: 10.1016/j.ijpharm.2022.122377. Epub 2022 Nov 9.
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.
本研究旨在评估利用桶内干燥是否可以在单次操作中实现湿颗粒的形成和干燥。为了选择合适的加工参数并评估在挤出机中短停留时间的可行性，研究了制剂的干燥动力学。18mm 挤出机以 40:1 的 L:D 比运行，有 8 个区。前两个区用于物料进料和湿颗粒形成，其余区用于在高温下干燥。研究了螺杆构型以及螺杆速度、进料速率和停留时间对干燥过程的影响，以优化干燥工艺。由于温度和停留时间的限制，添加了真空以实现充分干燥。在线近红外光谱被纳入双螺杆湿法造粒（TSWG）工艺中，以实时监测湿颗粒的水分含量。该装置进行了优化，并为未来的实验开发了预测模型。本研究首次在中试（18mm）挤出机上成功演示了该技术。颗粒在中等温度（100°C-110°C）下形成并干燥至目标干燥失重（LOD）小于 2%，单次操作即可完成。将湿法制粒和干燥简化为一个单元操作，可以对制药生产产生深远的影响，减少时间、占地面积和产品转移带来的环境暴露。
