The modified compressibility-based compactibility model for improved prediction of compaction properties of poorly...

Mechanical properties play a key role in determining manufacturability of tablet formulations. The improved understanding of these metrics through predictive tools is of practical interest to implement lean and fast formulation and process development strategies. This work explores the varying predictability of a previously reported compressibility-based compactibility model by Reynolds et al. (2017) investigating model compounds with diverse mechanical properties. While the porosity prediction remained unchanged, a modification of tablet tensile strength prediction was proposed accounting the complex bonding area-bonding strength (BABS) interplay. This integrated concept was tested on 24 diverse systems comprising binary, ternary and multi-component mixtures with diverse particle size, excipient matrix and variations in its mechanical properties. The modified model performed consistently except DCPA and is advantageous particularly for inverse prediction of compaction properties of poorly compressible materials from mixtures followed by multicomponent mixture predictions in the presence of BABS interplay where improved predictive accuracy was indicated by RMSE values. Additionally, the relevant mechanical property metrics, such as plasticity and bonding strength were reliably estimated implying the usefulness of the modified model for digital formulation development strategies.