Measurement of the particle density of small amounts of pharmaceutical powders using high-contrast micro X-ray computed tomography

Particle density is a fundamental and important physical property of powders. However, the widely used gas displacement pycnometry (GDP) method typically requires sample volumes in the gram range. In this study, we developed a method for evaluating the density of milligram-scale samples using X-ray computed tomography (XRCT). We used pharmaceutical powders, consisting of organic and light metallic elements, as subjects. The volumes of 24 pharmaceutical powders (2-160 mg) with various particle sizes and shapes were measured using an XRCT device with a resolution of 0.65-2.6 mu m (field of view: 1.33-5.32 mm). Copper and molybdenum targets were used as X-ray sources, providing high-contrast imaging for materials with low electron densities. The densities obtained using XRCT correlated well with those obtained using GDP, as indicated by a linear regression line with a slope of 1.0 passing through the origin. The coefficient of variation for six sequential measurements was 0.0070, suggesting high repeatability. Additionally, we investigated optimal experimental conditions, such as spatial resolution, X-ray sources, and measurement time, to enhance the quality of three-dimensional XRCT images. We found that images with a grayscale histogram peak separation of approximately one between the sample and other components (sample tube and air) yielded optimal results. This non-destructive technique has the potential to accurately measure the densities of small sample quantities and can contribute not only to the pharmaceutical field but also to other industries handling organic and light metallic powders.