Predicting and Controlling Attrition of Active Pharmaceutical Ingredients during Agitated Drying

Scale-up of agitated drying processes to minimize particle size changes in Active Pharmaceutical Ingredients (API) can be challenging. Particle 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 attrition observed at scale. Factors such as API characteristics, batch size, dryer geometry, residual solvent content, and the defined agitation protocol can impact the extent of attrition during drying. The development of new scale-down tools can provided a platform to study the mechanism for particle attrition during API manufacturing in a material sparing way. This work characterizes the propensity for particle attrition to occur by employing a laboratory agitated vessel 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. The application of this methodology for several different APIs will be highlighted.