Understanding die fill variation during mini-tablet production

Abstract

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 6mm, 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 3mm 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 3mm mini-tablets while suction fill was associated with that of 1.8mm 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.