A Scale-Up, Phenomenological Model Incorporating the Effect of Both Feed Frame Lubrication and Tumble Blending-Driven Lubrication on Tablet Mechanical Strength.

Abstract

In tablet manufacturing, mixing operations in tumble blending (TB) and in the feed frame (FF) of the rotary press can both increase lubricity, negatively influencing the tablet mechanical strength. While the TB-driven lubrication was systematically studied, no reliable bench-scale methods exist for the effect of FF lubrication. Because TB and FF mixing are usually two successive operations in tablet manufacturing, we developed a phenomenological model to incorporate the impact of TB-driven lubrication and the FF lubrication on the tablet tensile strength (TS). We noted that exponential decay functions can describe the evolution of the tablet TS as the function of the extent of TB, as well as the residence time in FF. Hence, the overall lubrication sensitivity can be modeled by incorporating two distinct exponential decay functions. The model can be calibrated through bench-scale experiments. Using an investigational powder blend, we showed that this approach accurately predicted the tablet TS in a scale-up tablet compression study, thereby verifying its utility. This model can serve as a scale-up diagnostic and risk-assessment tool, with the ability to adjust the overall effect of lubrication by changing the TB scale and the FF residence time commensurate with the large-scale operations.