Scale-Up of Agitated Drying: Effect of Shear Stress and Hydrostatic Pressure on API Powder Properties

Roughly 80% of commercial pharmaceutical products utilize oral solid dosage formulations. In these formulations, the Active Pharmaceutical Ingredient (API) particle size can influence stability, bioavailability, dissolution rate and content uniformity of the drug product. For this reason, the pharmaceutical industry devotes significant effort to developing fundamental understanding of the processes that govern API particle size. Much of that effort has historically focused on crystallization development, whereas fundamental understanding of particle agglomeration and attrition in the subsequent agitated drying step is less well established. One reason is that traditional laboratory drying equipment has not successfully reproduced the degree of agglomeration or attrition observed at scale. This work characterizes the propensity for particle attrition to occur at different stages of the drying process by employing a laboratory agitated dryer that has been modified to measure impeller torque and reproduce the range of hydrostatic pressures observed during scale-up. A workflow for assessing risk of API attrition at manufacturing scale is described.