In-die compressibility as a surrogate for lubrication-induced changes in tabletability.

Lubricants are indispensable in tableting, as their impact extends beyond facilitating ejection to altering compressibility and tablet strength. However, the extent to which lubrication affects in-die compressibility, and whether these effects can be exploited for tensile strength modeling, remains insufficiently understood. This study systematically investigated the effects of lubricant type (magnesium stearate, sodium stearyl fumarate), concentration, and blending time on microcrystalline cellulose, dicalcium phosphate anhydrous, and an ibuprofen-based formulation using compaction simulation and compressibility analysis. Regression analysis confirmed that lubricant effects were expressed in the early compression phase. A nonlinear white-box model, based on tablet mass and onset density, accurately modeled tensile strength with mean squared errors ≤ 0.20 MPa across all materials and settings within the investigated dataset. These findings demonstrate that lubrication-driven variations in tabletability are inherently captured in compressibility data, enabling robust characterization of tensile strength without explicit lubricant information. Beyond model development, this work advances the understanding of lubrication effects in compressibility-based modelling and highlights its potential as a formulation-independent strategy for tabletability assessment within quality-by-design frameworks.