Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
Janssen Pharmaceutica NV, 2340 Beerse, Belgium.
Int J Pharm. 2024 Aug 15;661:124357. doi: 10.1016/j.ijpharm.2024.124357. Epub 2024 Jun 17.
When tablets are manufactured on a rotary tablet press and the throughput is increased, it leads to changes in powder dynamics during die filling due to formulation characteristics and changing powder flow in the feed frame. This may result, a.o. in increased tablet weight variability, poorer content uniformity, capping and lamination. This research focuses on explaining the die filling performance depending on material properties and process settings, including throughput for small and large tablets. It was concluded that throughput had a negative impact on die filling variability, which is related to reduced residence time and lower fill fraction of the feed frame and dies. Furthermore, the die filling mechanism was inherently different for large tablets in comparison to small tablets. Higher die filling consistency was observed for dense, less porous, less compressible and better flowing powders. As a result of this work, a model was developed to predict the impact of formulation properties and process settings on die filling variability and its dependency on changes in throughput. This model will benefit formulation development at an early stage when active ingredient availability may be challenging as it will avoid the need to conduct experiments at high throughputs.
当片剂在旋转压片机上制造且产量增加时，由于配方特性和进料器中粉末流动的变化，会导致在压模填充过程中粉末动力学发生变化。这可能导致片剂重量变异性增加、含量均匀度变差、出现顶裂和分层等问题。本研究重点解释了取决于材料特性和工艺参数（包括小和大片剂的产量）的压模填充性能。研究结果表明，产量对压模填充变异性有负面影响，这与进料器和压模中的停留时间缩短以及填充分数降低有关。此外，与小片剂相比，大片剂的压模填充机制本质上有所不同。对于密度较高、多孔性较低、可压缩性较低且流动性较好的粉末，压模填充一致性更高。这项工作的结果是开发了一个模型，以预测配方特性和工艺参数对压模填充变异性的影响及其对产量变化的依赖性。该模型将在活性成分可用性可能具有挑战性的早期制剂开发阶段受益，因为它将避免在高产量下进行实验的需要。
