Kruisz Julia, Rehrl Jakob, Sacher Stephan, Aigner Isabella, Horn Martin, Khinast Johannes G
Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Automation and Control, Graz University of Technology, Graz, Austria.
Int J Pharm. 2017 Aug 7;528(1-2):334-344. doi: 10.1016/j.ijpharm.2017.06.001. Epub 2017 Jun 3.
Disturbance propagation during continuous manufacturing processes can be predicted by evaluating the residence time distribution (RTD) of the specific unit operations. In this work, a dry granulation process was modelled and four scenarios of feeding events were simulated. We performed characterization of the feeders and developed RTD models for the blender and the roller compactor based on impulse-response measurements via color tracers. Out-of-specification material was defined based on the active pharmaceutical ingredient (API) concentration. We calculated the amount of waste material at various diversion points, considering four feeder-related process-upset scenarios and formulated considerations for the development of a control concept. The developed RTD models allow material tracking of materials that may be used for following the spread contaminants within the process and for batch definition. The results show that RTD modeling is a valuable tool for process development and design, as well as for process monitoring and material tracking.
通过评估特定单元操作的停留时间分布（RTD），可以预测连续制造过程中的干扰传播。在这项工作中，对干法制粒过程进行了建模，并模拟了四种进料事件场景。我们对进料器进行了表征，并基于通过颜色示踪剂进行的脉冲响应测量，为混合器和辊压机开发了RTD模型。根据活性药物成分（API）浓度定义了不合格物料。我们计算了在各种分流点的废料量，考虑了四种与进料器相关的工艺扰动场景，并为控制概念的开发制定了考虑因素。所开发的RTD模型允许对可能用于追踪过程中污染物扩散和批次定义的物料进行物料跟踪。结果表明，RTD建模是用于工艺开发和设计以及工艺监测和物料跟踪的宝贵工具。
