The effect of intermittent mixing on flow, heating, and drying of granular materials in an agitated dryer
Creators: name: Chaksmithanont, Prin
Publisher: name: No Publisher Supplied
Year: 2022

description: Drying is a common unit operation in the manufacturing of active pharmaceutical ingredients (APIs). Understanding material properties, physicochemical stability, and drying kinetics are crucial for drying protocol development. However, the optimization of drying conditions is challenging because of simultaneous changes in heat and mass transfer, as well as material properties. Among the different types of dryers, agitated dryers are commonly used for API drying. During the process, a wet API bed is heated in a temperature-controlled cylindrical vessel while being mixed by a rotating impeller under a vacuum. Although agitation promotes heat and mass transfer, the shear stress acting on the API bed can result in particle breakage. To maintain a desirable drying rate while mitigating particle breakage, a common approach is to apply intermittent mixing, where the impeller is turned on and off. Yet, a lack of fundamental knowledge about how intermittent mixing affects the drying process obstructs the design and optimization of mixing protocols.In this dissertation, the influence of intermittent mixing on flow, heating, and drying of granular materials in an agitated dryer was studied. The processes were investigated using a combination of simulations and experiments. Basic knowledge was initially developed from constant mixing, and the investigation was then extended to intermittent mixing. First, the flow of granular materials was characterized by the shear stress acting on the powder bed, which can be related to the impeller torque. During periods of agitation, it was observed that the torque was independent of rotation rate and increased linearly with material bed height. The bulk friction coefficient and material cohesiveness were computed from a linear correlation between normal stresses and shear stresses in the particle bed. Torque predictions from the bulk friction coefficients exhibited good agreement with torque measurements. Next, heat transfer of granular materials was studied for intermittent mixing. The agitation ratio (the fraction of time when the impeller is on) and the intermittent cycle number (the number of times the agitator is turned on and off) represent the extent and allocation of agitation, respectively. It was observed that as the agitation ratio increases from the static bed (no agitation), the rate of heat transfer and temperature uniformity sharply increased with agitation ratio. However, a further increase in the agitation ratio gradually increased the rate of heat transfer and temperature uniformity. Additionally, the rate of heat transfer and temperature uniformity initially increased with intermittent cycle number, then reached a plateau. A power law fitting equation was proposed to predict heat transfer using intermittent mixing parameters. Lastly, the drying of granular materials was determined by the moisture content of the powder bed. Similar findings to heat transfer were found for the drying study, in terms of the drying rate, as a function of agitation ratio and intermittent cycle number. This work shows that intermittent mixing can have a strong impact on the rate of heat transfer and the rate of drying. Also, the results provide insights into the design of mixing protocols.