Purpose

Roll compaction/dry granulation is established in manufacturing of solid oral dosage forms and, within the context of continuous manufacturing, it has sparked interest as material is fed, processed, and ejected continuously while also providing large possible throughputs. However, this amount of material has to be adequately controlled in real time to assure quality.

Methods

This research aimed at monitoring the critical quality attribute granule size distribution in continuous roll compaction/dry granulation (QbCon®; L.B. Bohle, Ennigerloh, Germany) using in-line and on-line laser diffraction. The influence of varying process parameters and excipient formulations was studied and evaluated with the prospect of using this technique to develop control loops. For this purpose, residence time parameters were assessed. In- and on-line data was compared with off-line laser diffraction and dynamic image analysis data.

Results

The system successfully monitored the granule size distribution in a variety of process parameters and throughputs (up to 27.5 kg/h). It was sensitive to changes in process parameters and changes in material blends, which could pose a potential threat to the final drug products’ quality. Average event propagation time from the compaction zone to the laser diffraction system of 17.7 s demonstrates the systems’ fast reaction time.

Conclusion

Results highlight laser diffraction as a valuable method of in- and on-line size determination and allow for the development of a control strategy using this principle.

中文翻译：

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基于激光衍射的连续辊压制/干法制粒粒度在线分布在线监测系统的开发与评估

目的

辊压制/干法制粒建立在固体口服剂型的制造中，并且在连续制造的背景下，随着材料的连续进料，加工和排出而引起了人们的兴趣，同时还提供了可能的大产量。但是，必须实时地适当控制此数量的材料以确保质量。

方法

这项研究旨在通过在线和在线激光衍射监测连续辊压制/干法制粒（QbCon®； LB Bohle，Ennigerloh，德国）中关键的质量属性粒度分布。研究和评估了各种工艺参数和赋形剂配方的影响，并有望使用该技术开发控制回路。为此，评估了停留时间参数。将在线和在线数据与离线激光衍射和动态图像分析数据进行比较。

结果

该系统成功监测了各种工艺参数和产量（最高27.5 kg / h）中的颗粒尺寸分布。它对工艺参数的变化和材料混合物的变化很敏感，这可能对最终药品的质量构成潜在威胁。从压实区到激光衍射系统的平均事件传播时间为17.7 s，证明了系统的快速反应时间。

结论

结果突出了激光衍射作为在线和在线尺寸确定的一种有价值的方法，并允许使用此原理开发控制策略。