Reproducibility of die fill during tablet production is critical to ensure consistent tablet drug content and mechanical attributes. In the production of
mini-tablets, tablets smaller than 6 mm, achievement of uniform die fill is much more challenging. Powder flow is often associated with die fill accuracy but this relationship has not
been well characterised especially for mini-tablets. In this study, flow properties of different types of granules were characterised. Mini-tablets of 1.8 and 3 mm diameters were prepared from
the granules using a rotary press with multiple-tip compression tooling. A methodology was established to evaluate mini-tablet die fill variation within and across compaction cycles using data from
compression roller displacement and mini-tablet weight. Both sizes of mini-tablets showed similar extents of inter-cycle weight variation that could be associated with granules’ inter-particulate
friction. However, smaller mini-tablets had higher intra-cycle weight variation due to their narrower die orifices. Multivariate and univariate analyses suggested that gravity fill influenced
intra-cycle weight variation of 3 mm mini-tablets while suction fill was associated with that of 1.8 mm mini-tablets. Possible differences in die fill mechanisms between the mini-tablet
sizes were identified and this provided a better insight into die fill variations during the production of mini-tablets.