Wu Yu San, van Vliet Lucas J, Frijlink Henderik W, van der Voort Maarschalk Kees
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Int J Pharm. 2007 Sep 5;342(1-2):176-83. doi: 10.1016/j.ijpharm.2007.05.011. Epub 2007 May 16.
Porosity and pore structure are important characteristics of tablets, since they influence mechanical strength and many other properties. This paper proposes an alternative method for the characterization of pore structure based on image analysis of SEM micrographs. SEM images were made of sodium chloride tablets made with three different particle sizes. The pore size distribution in these images was determined with a technique referred to as a morphological sieve. The results were compared to the pore size distributions as obtained with mercury porosimetry. The SEM images display small cracks inside the grains and small 'floating' grains inside the pore space. As these artifacts are induced in sample preparation, they need to be identified and removed from the images before analysis. The influence of the size of the discarded structures on the total porosity and the pore size distribution was investigated. The small 'floating' grains prevented the determination of the size of large pores, but had a negligible effect on the porosity. The removal of small cracks inside the grains had no effect on the pore size distribution but a large effect on the porosity. Based on the comparison of these results with the experimentally determined porosity, a maximum size for the structures that were to be removed was determined. The resulting pore size distributions were in the same order of magnitude as the results obtained with mercury porosimetry. Both methods display a comparable relative shift of the pore size distributions to larger sizes for tablets with increasing particle size. Therefore, it can be concluded this image analysis technique is a good method for the characterization of pore structure.
孔隙率和孔隙结构是片剂的重要特性，因为它们会影响机械强度和许多其他性质。本文提出了一种基于扫描电子显微镜（SEM）显微照片图像分析来表征孔隙结构的替代方法。对用三种不同粒径制备的氯化钠片剂进行了SEM成像。利用一种称为形态学筛分的技术确定了这些图像中的孔径分布。将结果与压汞法获得的孔径分布进行了比较。SEM图像显示出颗粒内部的小裂缝以及孔隙空间内的小“漂浮”颗粒。由于这些伪像在样品制备过程中产生，因此在分析之前需要从图像中识别并去除它们。研究了丢弃结构的尺寸对总孔隙率和孔径分布的影响。小“漂浮”颗粒妨碍了大孔径的测定，但对孔隙率的影响可忽略不计。去除颗粒内部的小裂缝对孔径分布没有影响，但对孔隙率有很大影响。基于将这些结果与实验测定的孔隙率进行比较，确定了要去除的结构的最大尺寸。所得的孔径分布与压汞法获得的结果处于同一数量级。对于粒径增加的片剂，两种方法的孔径分布都显示出向较大尺寸的可比相对偏移。因此，可以得出结论，这种图像分析技术是表征孔隙结构的一种好方法。
