Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Int J Pharm. 2022 Aug 25;624:121950. doi: 10.1016/j.ijpharm.2022.121950. Epub 2022 Jun 23.
In this study, a concentration predicting soft sensor was achieved based on the Residence Time Distribution (RTD) of an integrated, three-step pharmaceutical formulation line. The RTD was investigated with color-based tracer experiments using image analysis. Twin-screw wet granulation (TSWG) was directly coupled with a horizontal fluid bed dryer and an oscillating mill. Based on integrated measurement, we proved that it is also possible to couple the unit operations in silico. Three surrogate tracers were produced with a coloring agent to investigate the separated unit operations and the solid and liquid inputs of the TSWG. The soft sensor's prediction was compared to validating experiments of a 0.05 mg/g (15% of the nominal) concentration change with High-Performance Liquid Chromatography (HPLC) reference measurements of the active ingredient proving the adequacy of the soft sensor (RMSE < 4%).
在这项研究中，基于集成的三步制药制剂线的停留时间分布（RTD），实现了浓度预测软传感器。使用基于颜色的示踪剂实验和图像分析研究了 RTD。双螺杆湿法造粒（TSWG）直接与水平流化床干燥机和振动磨耦合。基于集成测量，我们证明了也有可能在虚拟中耦合单元操作。使用着色剂生产了三种替代示踪剂，以研究分离的单元操作以及 TSWG 的固体和液体输入。将软传感器的预测与高效液相色谱法（HPLC）参考测量的活性成分的 0.05 mg/g（名义值的 15%）浓度变化的验证实验进行了比较，证明了软传感器的充分性（RMSE<4%）。
