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

Scale-up of agitated drying processes to minimize particle size changes in Active Pharmaceutical Ingredients can be challenging. Particle agglomeration or attrition problems due to agitated drying are often discovered upon the initial scale-up from the lab to the plant. Traditional laboratory drying equipment has not successfully reproduced the degree of agglomeration or attrition observed at scale. This discrepancy may be attributed to the ability of particulate solids, such as crystalline API’s, to transfer stresses from the normal direction into the shearing direction. As batch size increases during scale-up, the compressive and shearing forces experienced by the API increase. 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 compressive and shearing forces observed during scale-up.  A workflow for assessing risk of API attrition at manufacturing scale is described.