Scaling up Strategy for Continuous Powder Mixing Process

Comprehensive Quality by Design in Pharmaceutical Development and Manufacture
2011 AIChE Annual Meeting
AIChE Annual Meeting
October 19, 2011 - 8:00pm

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.


1. Johnstone RW, Thring MW, Pilot plants, models and scale-up methods in chemical engineering. 1957, MacGraw-Hill: New York.

2. Gao Y, Ierapetritou M, Muzzio F. Periodic section modeling of convective continuous powder mixing processes. AIChE Journal. 2011; . In Press: DOI: 10.1002/aic.12563.

Professional Development Hours
0.5 PDHs
You will be able to download and print a certificate for these PDH credits once the content has been viewed. If you have already viewed this content, please click here to login.

Would you like to access this content?

No problem. You just have to complete the following steps.

You have completed 0 of 2 steps.

  1. Log in

    You must be logged in to view this content. Log in now.

  2. Purchase Technical Presentation

    You must purchase this technical presentation using one of the options below.
    If you already purchased this content recently, please click here to refresh the system's record of ownerships.


Credits 0.5 Use credits
List Price $25.00 Buy now
AIChE Members $15.00 Buy now
AIChE Undergraduate Student Members Free Free access
AIChE Graduate Student Members Free Free access