Scaling up strategy for continuous powder mixing process
Yijie Gao, Fernando Muzzio and Marianthi G. Ierapetritou
Dept. of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854
Continuous powder mixing has attracted a lot of interest among pharmaceutical industry. Based on the principle of similarity proposed by Johnstone and Thring 1, many works have been done recently that target the scale-up of continuous powder mixing. In this work, a quantitative scale-up strategy is described that allows the transition from lab to industrial scale. By using the periodic section modeling developed in our previous study 2, scale-up of the cross-sectional mixing and scale-up of the axial mixing are separately considered. To capture the cross-sectional mixing component, the conception of variance spectrum is used. The Lomb-Scargle Periodogram technique widely applied in astronomical studies has been introduced to estimate the variance spectrum of unevenly distributed samples in powder mixing process. The effect of constant sample size on mixing performance of different scales is thus elucidated. To capture the axial mixing component, the residence time distribution is used to characterize mixing of different scales.
Two case studies are presented to illustrate the applicability of the developed strategy. For non-segregating mixing case, similar scale-up characteristics are observed for both cross-sectional and axial mixing. While satisfying the principle of similarity leads to similar decay contours of variance spectrum, a sampling size much smaller than scales of both mixers should be used to achieve similar measurements of mixing performance. A 2.5 power increase of flux rate is generally obtainable in the scale-up of non-segregating materials. However, in processes where cohesive materials are used, segregation occurs due to a tendency of agglomeration, and a larger increase of flow rate is observed. This results from the effect of cohesion on axial motion especially when the scale of mixing process is small. Our method can be used to provide specific guidance of scale-up of different powder mixing cases.
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