Modification of a scale-up model to improve prediction of the effect of lubrication on tablet tensile strength

Abstract

Kushner et al. proposed a scale-up model to describe the effect of lubrication on tablet tensile strength. In our study, a lubricant cohesiveness term, (1 + α/V), was added to the lubrication scale-up model reported by Kushner et al. to address the cohesiveness of magnesium stearate. The modified model proposed is as follows: TSSF=0.85 = TSSF=0.85,0[β(1 + α/V)exp(−ϒ × 1.5 V1/3 × Fheadspace × r) + (1 − β)], where TSSF=0.85 is tablet tensile strength at solid fraction 0.85, V is blender size, Fheadspace is fraction of headspace, r is revolution number, TSSF=0.85,0 is theoretical initial tensile strength, α is the sensitivity constant of magnesium stearate powder cohesiveness, β is the sensitivity constant of the blend to lubrication, and γ is the lubrication rate constant. Using a high shear placebo granule, lubrication scale-up models were built using both equations, with and without the cohesiveness term, and tested by a 16-fold scale-up. The equation with the cohesiveness term demonstrated superior prediction of tablet tensile strength for scale-up within the selected granular system and the scale-up range studied in this work, indicating the usefulness of including magnesium stearate powder cohesiveness in building a scale-up predictive lubrication model using an active pharmaceutical ingredient (API) sparing approach with small quantity of materials.