(605b) CFD Analysis of Micro and Macro Mixing for Robust Scale-up of Addition Rate and Impellor Speed

The local mixing
mechanism at the point of addition of reagent to a reaction mass can play
significant role in achieving the target quality of the product, particularly
if the reaction process is mixing driven or in the other words for the scenarios
where the reaction time scales are much faster than the mixing time scales. In
these cases, it is key to understand the relative influence of mixing time
scales (micro controlled vs. macro controlled mixing) on the API product
quality attributes such as particle size and molecular weight distribution.

At lab scale, the
addition rate of reagent to the reaction mass and the impellor speed was found
to impact the final size distribution of nano-particles. It has been hypothesized
that if the macro-mixing is faster than the micro-mixing, then the
nano-particles that are resulted from the reaction at the end of dip tube
disperse faster without any agglomeration and vice versa. Furthermore, the
macro-mixing time [1] scale is a function of addition rate (Q), local fluid
velocity (u) and turbulent energy dissipation (ε) at the point of addition
as given by equ. (1), while the micro-mixing time [1] is a function of
kinematic viscosity (ν) and turbulent energy dissipation (ε) as given
by equ. (2). 

                                                       
(1)

                                                   (2)

The effect of
process parameters such as addition rate of reagent, location of dip tube
impellor speed and impellor configuration on the mixing time scales at lab,
pilot and plant scales have been investigated using CFD simulations. The
un-steady RANS with k-ε as turbulence closure model was used. VOF model
was used to track the surface vortex during the agitation. The following two
criteria have been identified to establish the sameness between lab and plant
scale:

a. The local
bulk velocity distribution should be kept same (as shown in Fig. 1)

b. At the point
of addition, the ratio of meso to micro mixing should be kept same (as shown in
Fig.2)

Using the data
from the simulation, a design chart as shown in Fig.2 was generated to link the
time scale ratio of R&D, pilot and plant scale vessels under different
operating conditions, impellors. This chart was used as a control strategy to finalize
the parameters for the plant scale leading to successful scale-up.

Fig. 1 Comparison of velocity
distribution across the scales at different impellor speeds.

Fig. 2 Ratio of meso to micro mixing time
scale as funtion of addition rate across the scales.ss

References

[1] Bałdyga, J., Bourne, J.R. and Hearn, S.J., 1997.
Interaction between chemical reactions and mixing on various scales. Chemical
Engineering Science, 52(4), pp.457-466.

[2] Jahoda, M., Moštěk, M., Fořt, I.
and Hasal, P., 2011. CFD simulation of free liquid surface motion in a pilot
plant stirred tank. The Canadian Journal of Chemical Engineering, 89(4),
pp.717-724.