Development and Application of Laboratory Tools To Predict Particle Properties upon Scale-Up in Agitated Filter-Dryers

Agitated filter-dryers (AFDs) are commonly used for performing both filtration and drying operations in the manufacture of active pharmaceutical ingredients (APIs) and intermediates. Successful scale-up from the laboratory to manufacturing AFD equipment requires that physical properties specifications such as particle size be consistently met in addition to chemical purity specifications. Depending on the API–solvent system and equipment operational parameters, undesired attrition or agglomeration may occur, so an improved understanding of these phenomena upon scale-up is of key importance. In this paper, we describe recent advances in laboratory methods, based on material characterization methods common to drug product formulation development, to better assess the risk of agglomeration and attrition potential upon scale-up. These methods provide data to evaluate solid behavior, in both wet and dry states, associated with processing in an AFD. For agglomeration prediction, the application of mixer torque rheometry for measuring the propensity to form granules or agglomerates of API wet cake is described as well as how to categorize agglomeration risk based on the output of this testing. For measuring attrition propensity, the application of powder rheometry is described, and risk categories are proposed. For both testing methods, good agreement was seen between laboratory predictions and actual behavior upon scale-up. For compounds evaluated as high risk for attrition or agglomeration, alternate drying protocols are recommended to mitigate risk. In addition, progress on enhancing cycle times for difficult to dry materials is discussed.