New approach to optimizing risk management of the sticking problem using scale-independent critical material attributes and the quantitative process parameter

In pharmaceutical manufacturing of solid formulations, blending with a lubricant is a key process in preventing sticking during compression. Sticking not only results in tablets with a disfigured appearance but also brings about the interruption of continuous operations. The aim of our study was to identify blending scale-independent critical material attributes (CMAs) in relation to the sticking problem to appropriately define the end-point of the blending process with magnesium stearate as lubricant. Results showed that the dispersive surface free energy (SFE) and the specific free energy absorptions (AGsp) of ethanol decreased during blending with magnesium stearate. As the two parameters decreased, the sticking problem was improved. In conclusion, we propose that the dispersive SFE and AGsp of ethanol are scale-independent CMAs, and that the minimum blending time (BTmin), which can be calculated from the two CMAs, of the quantitative process parameter show the minimum blending time required to achieve higher risk assessment of the sticking problem.