(267a) Agitated Drying of Active Pharmaceutical Ingredients: Effect of Intermittent Mixing on Heat Transfer

Drying is a common unit operation in the upstream processing of active pharmaceutical ingredients (APIs). Although several drying methods have been used in the pharmaceutical industry, agitated drying is a common approach for API drying. During the process, wet particles are heated in a jacketed cylindrical vessel while being mixed by a rotating impeller until the product reaches the desired moisture content. An incomplete understanding of the process can result in operating problems such as under or over drying, non-uniform drying, polymorphism changes, agglomeration, and particle breakage. Moreover, it is difficult to choose the operating conditions to optimize the process due to several phenomena including mass transfer, heat transfer, and changes in material properties which occur simultaneously in an agitated dryer. Even though agitation promotes convective drying, the shear stress acting on the bulk material can result in particle breakage. In previous work, it has been observed that particle breakage is independent of rotation speed and dependent on the number of impeller revolutions.

The discrete element method (DEM) has been used previously to examine heat transfer for particle-particle and particle-wall conduction for a dry bed of particles. The rate of heat transfer can be described by a heating time, which is the time required to heat the bulk material to a fraction of the wall temperature. In this study, we simplified the problem and focused specifically on how to maximize heat transfer while minimizing particle breakage during the drying process. We performed DEM simulations using intermittent mixing, defined as alternate stirring and non-stirring periods of the impeller, as an approach for minimizing particle breakage by decreasing the number of impeller revolutions. We found that the heating time initially decreased with increasing impeller revolutions and then reached a plateau. For a single cycle of intermittent mixing, the starting time of the stirring period influenced the heating time. Moreover, for multiple cycles of intermittent mixing with similar number of impeller revolutions, the heating time of the material bed decreased with increasing intermittent mixing cycles to a certain point and then reached a plateau. When we calculated the relative stirring time (RST), the ratio of stirring time per cycle, we found that intermittent mixing beds with similar RST and number of impeller revolutions gave similar heating time within a certain range of number of impeller revolutions. This work provides insight into how intermittent mixing can be optimized during the drying process in order to maintain effective heat transfer while diminishing particle breakage. This work was partially supported by Takeda Pharmaceuticals International Co.