Single-particle geometries of pharmaceutical powders from X-ray tomography; a simple and reliable sample preparation method

The size and shape of the particles within a powder are critical quality-control attributes in the pharmaceutical industry. These microscopic attributes significantly affect the macroscopic properties of the powder, such as the bulk density and flowability. Methods for determining the particle size distribution (PSD) and characterisation of particle shape are therefore essential but can be extremely challenging, particularly when looking at individual particle shapes. This work introduces a new sample preparation method for X-ray micro-computed tomography (μCT) that is convenient, fast, and produces well-dispersed samples, allowing the identification of individual particles. The resulting contrast is excellent even for organic pharmaceutical powders, which are often challenging to image due to the low attenuation coefficient of their components. Simultaneously, an analysis method is proposed that reliably applies to all tested powders, automatically filtering out artefacts such as bubbles. The combined method unambiguously identifies individual particles, allowing the determination of PSD, particle shape classification, and analysis of the internal morphology of particles. Validation is provided through comparisons with laser diffraction, sieve analysis, and optical microscopy. While this new standardised μCT method is slightly more labour intensive than other characterisation methods, it requires only a minimal amount of material (∼15 mg) and provides superior morphological information, which can be used to help explain or predict bulk properties. This is particularly beneficial in early-phase development, where access to large quantities of powder is limited.