Development of new laboratory tools for assessment of granulation behavior during bulk active pharmaceutical ingredient drying.

Approximately 30% of active pharmaceutical ingredients (APIs) experience agglomeration, granulation, and breakage during agitated drying. Currently, there is no small-scale bench tool to help assess and observe granulation behavior of APIs in the laboratory and subsequently lead to the development of a robust drying method. As a result, more conservative drying methods are usually used at scale and much longer drying times are needed. In this work, we build on work reported in the literature and demonstrate that a mixer torque rheometer (MTR) can be a useful small-scale tool to flag potentially problematic granulation behavior of APIs under different conditions. The results from the MTR were confirmed using a second new tool involving the use of an acoustic mixer to verify and observe the granulation behavior on a small scale. We also show consistency between the data collected at the laboratory and the pilot plant scales.