Scale‐up of agitated drying: Effect of shear stress and hydrostatic pressure on active pharmaceutical ingredient powder properties

Abstract

Scale‐up of agitated drying processes to minimize particle size changes in active pharmaceutical ingredients (API) can be challenging. Particle agglomeration or attrition problems due to agitated drying are often discovered on 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. To overcome this limitation, a modified laboratory setup was constructed which reproduces the range of hydrostatic pressures observed during scale‐up. This work highlights the use of the modified setup to characterize the propensity for particle attrition to occur at different stages of the drying process by measuring impeller torque. Torque measurements of the API powder at different hydrostatic pressures revealed a behavior consistent with Coulomb's law of friction. The torque data obtained from these measurements were used to determine the bulk friction coefficient for API powder beds at different liquid content. Additionally, the amount of work done by the impeller blades was correlated to the degree of particle attrition observed. A workflow for assessing risk of API attrition at scale is described. © 2014 American Institute of Chemical Engineers AIChE J, 61: 407–418, 2015