Investigation of particle packing in model pharmaceutical powders using X-ray microtomography and discrete element method

This paper outlines a novel technique, based on combination of modern desktop X-ray microtomography, quantitative image processing and computer simulation using the discrete element method (DEM), to investigate randomly packed particles in an attempt to model the process of pharmaceutical tablet manufacture by powder compaction. The systems studied include glass ballotini and spheroidal micronised cellulose (Celphere), all with typical particle sizes between 180 and 300 μm. We demonstrate that X-ray microtomography (XMT) and DEM can reproduce the structure of real packing systems in three-dimensions and have the potential for further investigation of pharmaceutical processes by both modelling and experimental study. This was achieved by generating packing systems using DEM simulations that are consistent with the structural measurements made by XMT on real packed powders via the comparison of their radial distribution functions (RDFs). These results have been validated by direct volume measurements, and scanning electron microscopy (SEM) observations in terms of particle morphologies and size distribution. The result is a significant step forward for the quantitative analysis of model systems for pharmaceutical powders.