Purpose

This work details experimental observations on the effect of liquid flow percolating through packed beds of crystals to elucidate how the filtration pressure severely alters the size distribution and crystal shape. Pressure filtration is widely used in the pharmaceutical industry, and frequently results in undesired size distribution changes that hinder further processing.

Methods

The percolation methodology presented fixes fluid flow through a bed of crystals, resulting in a pressure over the bed. X-ray computed tomography (XCT) provided detailed observations of the bed structure. Detailed 2D particle size data was obtained using automated microscopy and was analysed using an in-house developed tool.

Results

Crystal breakage is observed when the applied pressure exceeds a critical pressure: 0.5–1 bar for ibuprofen, 1–2 bar for β-L glutamic acid (LGA) and 2–2.5 bar for para amino benzoic acid (PABA). X-ray computed tomography showed significant changes in bed density under the applied pressure. Size analysis and microscope observations showed two modes of breakage: (i) snapping of long crystals and (ii) shattering of crystals.

Conclusion

LGA and PABA have a similar breakage strength (50 MPa), ibuprofen is significantly weaker (9 MPa). Available breakage strength data may be correlated to the volumetric Gibbs free energy. Data from 12 and 35 mm bed diameters compares well to literature data in a 80 mm filter; the smaller, easy to operate percolation unit is a versatile tool to assess crystal breakage in filtration operations.

中文翻译：

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连续渗滤作用下滤床中高纵横比晶体的破碎

目的

这项工作详细介绍了对液体流通过晶体填充床渗透的影响的实验观察，以阐明过滤压力如何严重改变尺寸分布和晶体形状。压力过滤广泛用于制药行业，经常会导致不希望的尺寸分布变化，从而阻碍进一步加工。

方法

所介绍的渗透方法固定流体流过晶体床，从而在床上产生压力。X 射线计算机断层扫描 (XCT) 提供了对床结构的详细观察。使用自动显微镜获得详细的 2D 粒度数据，并使用内部开发的工具进行分析。

结果

当施加的压力超过临界压力时观察到晶体破裂：布洛芬为 0.5-1 巴，β- L 谷氨酸 (LGA)为 1-2巴，对氨基苯甲酸 (PABA) 为 2-2.5 巴。X 射线计算机断层扫描显示在施加压力下床密度发生显着变化。尺寸分析和显微镜观察显示了两种破损模式：(i) 长晶体的折断和 (ii) 晶体的破碎。

结论

LGA 和 PABA 的断裂强度相似（50 MPa），布洛芬明显弱一些（9 MPa）。可用的断裂强度数据可能与体积吉布斯自由能相关。12 和 35 毫米床径的数据与 80 毫米过滤器的文献数据相得益彰；更小、易于操作的渗滤装置是一种多功能工具，可用于评估过滤操作中的晶体破损情况。