Scale-up strategy for continuous powder blending process

a r t i c l e i n f o Continuous powder mixing has attracted a lot of interest within the pharmaceutical industry. Much work has been done recently that targets the characterization of continuous powder mixing. In this paper, a quantitative scaling up strategy is introduced that allows the transition from lab to industrial scale. The proposed methodology is based on the variance spectrum analysis, and the residence time distribution, which are key indexes in capturing scale-up of the batch-like mixing, and scale-up of the axial mixing and motion, respectively. Our simulation results are used as preliminary guidance for scaling up different powder mixing cases. Powder mixing is a significant unit operation in food, cement, and many other industrial fields. In the pharmaceutical industry, the concentration variability of active pharmaceutical ingredient (API) in each tablet directly depends on the quality of powder mixing in upstream unit operations. Batch processing provides reliable quality and process control when small volumes of powder are processed. While a traditional powder mixing process is typically performed in small batches, the recent development of continuous powder mixing processes has attracted a lot of interest due to its capacity in handling high flux manufacturing. Reviews on both batch [1–3] and continuous powder mixing [4] reflect our current understanding on these topics. Previous work in the area of powder mixing scale-up is based on the principle of similarity proposed by Johnstone and Thring [5]. According to this principle, the material flow patterns in two scales of mixing apparatuses are expected to be similar when the dimensions, velocity fields, and force distributions of corresponding points are proportional to each other. Generally, dimensional analysis is applied to identify these similarity criteria if the process governing equations are unknown , while dimensionless forms are derived if the governing equations are available. Applying this principle, Wang and Fan [6] investigated the scaling up of tumbling mixers. Their results indicate that the ratio of centrifugal force to the gravitational force, or the Froude number , can be used as the main similarity criterion for the scale-up of a tumbling mixer. Based on hydrodynamic similarity, Horio et al. [7] developed a scale-up rule for fluidized beds when the similarities in bubble coalescence, bubble splitting, and interstitial flow pattern are satisfied. Surface velocity profiles in rotating cylinders were found to follow simple scaling rules through the normalization of a one-dimensional motion equation with …