Effects of Comilling on Final API Physical Attributes

Abstract

Severe operational challenges were experienced during the delumping (via comilling) of a shear-sensitive active pharmaceutical ingredient (API) during a pilot plant campaign. During the in-line comilling operation from the dryer, the API melted and blinded the screen, which compromised the equipment and called the batch fitness for formulation into question. These challenges instigated the investigation of comilling parameters and API physical properties, and their respective effects on delumping performance as well as the final API attributes. Comil impeller speed, impeller type, screen hole size, and screen hole type were studied at both pilot plant and lab scale. The unique properties of the API were also studied in order to understand how this solid differed from others. Because solids with similar physical properties to the API in question are likely to behave in a similar way, the experimental approach described here for comil and solid characterization should be applicable to other projects as well. The optimal comilling conditions for the API were determined and demonstrated robustly at pilot scale.