Applicability of the Vreeman-Sun equation - power law mixing rule (VS-PL) model for predicting tabletability of mixtures.

Tabletability, which quantifies a powder's ability to be transformed into a tablet with a specified mechanical strength under an applied compaction pressure, is a critical material property in tablet formulation development. A predictive model based on the Vreeman-Sun equation, combined with a power-law mixing rule (VS-PL), has recently been proposed to estimate the tabletability of binary mixtures from those of individual components. In this study, the applicability of this model across diverse materials and formulation conditions was systematically evaluated using sixty unique binary mixtures, two ternary mixtures, and one five-component system comprising common pharmaceutical excipients and active pharmaceutical ingredients. The model demonstrated good predictive performance for most binary mixtures and accurately predicted the tabletability of the ternary mixtures and the quinary formulation. Particle size variation (30-180 µm) was found to have minimal impact on model performance within the investigated systems, and the model was applicable to formulations lubricated with magnesium stearate. However, predictions were less reliable for formulations involving very hard materials and compositions below the percolation threshold. Despite these limitations, the predictive framework has the potential to facilitate material-sparing and efficient digital design of high-quality tablet formulations.