Laboratory of Solids Process Engineering, TU Dortmund University, Dortmund, Germany.
Leistritz AG, Nuremberg, Germany.
Eur J Pharm Biopharm. 2019 Sep;142:396-404. doi: 10.1016/j.ejpb.2019.07.009. Epub 2019 Jul 8.
Hot-Melt-Extrusion on Twin-Screw-Extruders has been established as a standard processing technique for pharmaceutical products. A major challenge is the transfer from a lab to a production level, since the combination of several unit operations within one apparatus leads to complex conditions for such a continuous manufacturing process. Here the residence time distribution is a crucial measure, which reflects the different mechanisms, e.g. dissolution, mixing or degradation, during processing. In the first part of a Scale-Up study, a methodology for the optimization of an extrusion process with respect to the load and throughput is presented. The developed concept was applied for different extruder scales in order to compare the identified processing windows. A deviation of the dominant material heating mechanisms was observed for the different scales, while the constraints for the transfer of a process to a different scale by the developed optimization concept is demonstrated. Finally, a sufficient operating point on a reference extruder is identified and in the second part of this study, different concepts from literature are applied for the transfer of this Hot-Melt-Extrusion process to two larger scales. The focus of the investigations was on the impact of the different approaches on the residence time distribution and the comparison. The determined results revealed a change of the most sufficient approach for the two different extruder sizes. The impact on the location in the time domain and form of the distribution are discussed and additionally evaluated by the fit to a RTD-model. In conclusion, the ratio of the applied energy for transport to mixing is identified as valuable addition in this context.
双螺杆挤出机上的热熔挤出已被确立为药物产品的标准加工技术。一个主要的挑战是从实验室到生产规模的转移，因为在一个设备中结合了几个单元操作会导致这种连续制造过程的复杂条件。在这里，停留时间分布是一个关键的衡量标准，它反映了加工过程中的不同机制，例如溶解、混合或降解。在放大研究的第一部分中，提出了一种针对挤出过程的负载和吞吐量进行优化的方法。所开发的概念应用于不同的挤出机规模，以比较所确定的加工窗口。观察到不同规模的主导材料加热机制存在偏差，而通过所开发的优化概念将过程转移到不同规模的限制也得到了证明。最后，在参考挤出机上确定了一个足够的操作点，在本研究的第二部分，文献中的不同概念被应用于将这种热熔挤出过程转移到两个更大的规模。研究的重点是不同方法对停留时间分布和比较的影响。确定的结果显示，对于两种不同的挤出机尺寸，最有效的方法发生了变化。讨论了对时间域中位置和分布形式的影响，并通过与 RTD 模型的拟合进行了额外的评估。最后，将运输和混合所需的能量比确定为该背景下的有价值的附加项。
