isiMix Technology - Simulation of Mixing Processes
1. The First and the only tool in the Industry
2. Reliable and accurate results
3. Based on More Than 300 Man Years of R&D and Industry Experience
4. Replacing Pilot Experiments
5. Accelerated Time-to-Market process
6. User Friendly and easily accessible
http://visimix.com/
5. Common Questions
Did we cover the main parameters during the process
development?
Will our facilities will be appropriate for the developed
process?
Does the equipment offer is good for the process?
What about safety and runaway scenario?
Do our process is robust?
Does the operational range parameters are large enough for
the manufacture facilities?
09/06/2015 5
6. The Goal
Once the Science of the process (Chemistry, Biology or physics) is
known well, a common situation during the process transfer from lab to
production or from site to site is the gap between the old and new
results.
Our first goal is to develop a process that will run properly in
the first trial on a new scale or site, similar to our successful
results in the lab or in the old facility.
In order to achieve this, we need to evaluate the process with the same
conditions we will have in the production phase.
The main parameters we change are the hydrodynamics of
the system. If we are able to identify and control these
parameters we will be able to achieve to the available and
optimal solution.
09/06/2015 6
10. Typical Mixing Parameters
Application * Key process and scale up parameters
Newtonian/ Non Newtonian Hydrodynamics
and scale up
•Circulation flow rate
•Local turbulence values
•Shear rates
Blending- Single Phase mixing •Macro and micro mixing times
•Max./ Min. concentration difference C
Suspension, Crystallization, Dissolution •Max. local conc’s
•Max. shear rate
•Crystal collision energy
Liquid liquid mixing
Emulsification, Heterogeneous org. synth.
•Drop size dist.
•Surface specific mixing time
Gas injection, Absorption, Gas liquid reactors •Gas hold up
•Specific surface
•KL a- spec. mass trans. rate
Biotechnology •Oxygen mass transfer rate
Heat transfer in tanks with different
heat/cooling devices
•Media temp’
•Heat transfer coeff.
•Specific heat/cool rate
09/06/201510
11. Flow chart of the mathematical model and calculations
INITIAL DATA
EQUIPMENT SUBSTANCES REGIME
[type, design, size] [phases, composition, properties] [flow rates,
process parameters]
HYDRODYNAMICS
power consumption, circulation rate, forces, flow pattern, local
flow velocities
TURBULENCE
Macro-Scale Turbulent Mixing Micro-Scale Local Turbulence
Distribution of Turbulent Dissipation
MODELING OF MACRO-SCALE AND MICRO-SCALE
MIXING-DEPENDENT PHENOMENA
single-phase mixing, pick-up of solids, solid distribution, drop
breaking, coalescence, heat transfer, heating/cooling dynamics,
mass transfer,etc.
DYNAMIC CHARACTERISTICS OF MIXING-
DEPENDENT PROCESSES AT THE TRANSIENT STAGE
09/06/201511
12. A simplified scheme of mixing in the turbulent regime
1 - Central zone;
2 - peripheral zone
3 - upper level of liquid
4 - shaft
5 - torque
6 - wall
7 - agitator’s blade
q - circulation flow rate;
D - eddy diffusivity
Wax - average axial
circulation velocity
09/06/201512
14. VisiMix Model
Main Purpose of VisiMix Modeling :
Analysis of processes based on simulation of
mixing-dependent phenomena
09/06/201514
15. Basic Characteristics of VisiMix
Physical Models
• All the initial assumptions are based on
fundamental scientific data.
• All parameters of the models are functions of basic
flow characteristics, and not of the equipment
specific features.
• All experimental coefficients in the equations have
a clear physical meaning and are defined by
independent measurements.
• The results of modeling are always verified by
experiments with agitators and tanks of different
types and sizes.
• All the calculation methods have passed a stage of
industrial applications.
09/06/201515
16. General Equilibrium of Momentum:
T
R
(r)dr;tgv
RtgV;
V
ρwHfπR
wall
M
T
tg
T
0
1
2
2:wallofResistance
2
2
;
r
r
(r)dr/
tg
vρihiZiς
i
or M
)
i
(rtgv
ibihiZiςiM r
2
1
2
2
2
2
:devicesInternal
0 iΣM
bot
M
wall
MimpΣM
;
2
2
:kAgitator rtgr-voωrdr; U
R
(r)Uρ
bl,k
h
bl,k
Z
imp,k
Z
bl,k
ς
imp,k
M
imp
inr
09/06/201516
The mathematical description of the tangential flow is based on the
momentum balance. For steady state conditions, the general
equilibrium is presented as the balance of the agitator torque and
flow resistance moments of the tank wall, its bottom and baffles;
these moments are expressed in terms of flow resistance and
calculated using empirical functions for the resistance factors (fw, fbl,
etc.,)
19. Local equilibrium of momentum
;0 shearresimp dMdMdM
;
2
)(2
rdr
rU
hZZdM
imp
in
R
r
blblimpblimp
;2
2
)(
)( 2
2
drr
rv
rfdM
tg
bot
);(2 2
rHddMshear
;
dr
dv
turb
dr
dvLturb
2
Agitator:
Resistance:
Shear:
09/06/201519
The system includes also an equation of the turbulent
transfer of shear momentum expressed in terms of the
"mixing length of Prantl" hypothesis :
20. Prandtl’s Mixing Length
•Analogous to the kinetic theory of gases
•Used because ‘it works’
Suppose ‘lumps’ of fluid move
randomly from one shear layer
to another, a distance l apart.
This carries momentum and the
velocity difference must
therefore be related to the
turbulence
y
y1
y2
l
(y)u
21. Kolmogorov Representation
• The large eddies absorb the kinetic
energy from the main flow provided
their characteristic frequency u/L is
tuned to the frequency of the main
flow. L is the scale of large eddies
• The energy supplied at the highest
hierarchical level, corresponding to
the largest length scale L, is expanded
to induce motions at the lower levels
characterized by smaller length λk.
Within a wide inertial interval
(Kolmogorov scale) both dissipation
and external supply energy are
negligible, and thus energy is only
transferred from one mode to
another.
Visimix.Ltd21
23. Axial circulation
;axtgbl PPPP
;
2
sin)(
3
dr
vr
hZP
imp
in
R
r
tgimp
blblblbl
;
2
)( 3
3
tgw
bftg
bfbfbftg VHRf
Rv
SZP
,2
2
0
2
z
z
ubltgax HrQ
V
PPPP
;
0rr
z
turbz
dr
dv
dr
dv
Lturb
2
Total consumption of power:
Impeller blades :
Tangential flow :
Axial circulation :
09/06/201523
The description of the meridional circulation is based on the analysis
of energy distribution in the tank volume, and the calculations are
performed using the results of modeling of the tangential flow.
31. 31 Visimix.Ltd
QbD Methodology
(J.M. Berty, CEP, 1979)
LABORATORY
(R&D)
BENCH SCALE
(RC1,Mini Pilot)
PILOT
Demo – Simulation
(Visimix, Dynochem,CFD)
PLANT
(Production)
LABORATORY
(R&D)
BENCH SCALE
(RC1,HEL)
PILOT
(Mini Pilot)
PLANT
(Pilot, Production)
Scale
Down
Final
Design
Build
Design Analyze
New Process with Mixing
32. Lab and Prod
Calculations
Moshe Bentolila, Roberto Novoa, and Wayne Genck, Michal Hasson, Efrat Manoff, "Computer Aided Process
Engineering at Chemagis" , PHARMACEUTICAL ENGINEERING July/August 2011. 30-38 09/06/201532
33. Non ideal stirring – non homogeneity
• Before performance of scale up experiments VisiMix
simulation was used to check suspension at different Mini
Pilot Reactors:
Reactor 7603 7605 7605 7607
Volume, L 10 25 25 50
RPM 500 (Max) 400 500 (Max) 150 (Max)
Main
Characteristic
Liquid – Solid
Mixing
Solid suspension
quality
Complete
suspension is
questionable.
Partial settling of
solid phase may
occur.
Complete
suspension is
expected.
Complete
suspension is
expected.
Complete
suspension is
questionable.
Partial settling of
solid phase may
occur.
Max. degree of non
uniformity of solid
distribution
AXIAL, % 22.3 10.3 29.1 132
RADIAL, % 65.7 34.3 76.3 90.8
Not all Mini Pilot reactor are capable of full suspension of
POCA.
33
34. Methodology
In the three years since the commencement of this process, their engineers
achieved a high level of proficiency in the use of the simulation models in
order to analyze the results as a function of the process operational
parameters.
After three years of working with this integrated plan – they have summarized
their knowledge and experiences up to this point, as follows:
1. VisiMix products, when integrated in the validation process (up until they
achieved a stable process and confirmed the production) – helped to
reduce the number of lost production batches (each batch valued in
millions of dollars) - from 100 to just under 10 batches – (review slide 25)
2. VisiMix program used in conjunction with another simulation tool - as
reported in this presentation - contributed to the improvement of the
teamwork style and professionalism. Net results were observed throughout
the implementation of the new solution in better project development: EOR
(end of reaction) time reductions, projects development time and cost
reduction, and in addition - increasing the expertise and qualification level of
the professional staff.
The presentation can be review on the Visimix Website in the References -
Users Publications page. (Scale up optimization using simulation experiments-Chemagis
presentation) 09/06/201534
41. Reaction-Reported Examples
Bromination of 1,3,5-trimethoxybenzene
1,3,5-trimethoxybenzene (A) offers three equally relative
sites where halogen (B) can substitude one hydrogen atom.
The rate constants k1, k2 and k3 for successive substitution are
not 3:2:1 because of the strong deactivation of subsequent
electrophilic substitutions by halogens.
Because k1>>k2>>k3 much more R (monobromo) and S
(dibromo) should finally be present starting from
approximately equimolar quantities of A and B (b~1).
The methoxy group strongly activates bromination and
measured product distributions show substantially more S
than would be expected knowing that k1>>k2.
(J.R. Bourne & F. Kozicki “ Mixing effects during the bromination of 1,3,5, -
trimethoxybenzene” Chem. Eng. Sci. 32 (1977) 1538)
43. Reaction-Reported Examples
Hydrolysis of ethyl monochloroethanoate and neutralisation of HCl.
The following reactions compete for NaOH (the limiting reagent) and have been widely
used
NaOH + HCl -> NaCl + H2Ok1
NaOH + CH2ClCOOC2H5 -> C2H5OH + CH2ClCOONak2
In such experiments alkali is added to a stirred, acidic ester solution.
Rate constants at 298K are
k1 = 1.3 x 108 m3/mol.s
k2 = 0.030 m3/mol.s
the product distribution can berepresented by the yield of alcohol relative to the
limiting reagent (B) and denoted by XQ.
XQ = Q/Bo
J. Baldyga and J.R. Bourne, “Turbulent Mixing and Chemical Reactions” Wiley (1999)
44. Reaction-Reported Examples
S - just below the liquid surface
XQ = 0.266
D - in discharge stream of turbine
XQ = 0.153
I - in suction stream of turbine
XQ = 0.138
46. ProcessesMixing Parameters for Crystallization
For calculation of the Mass transfer coefficient, it is
necessary to enter a number of additional initial data,
including the Diffusivity of the solute. In our case the
problem consists not in prediction, but in reproduction
of the same value of the Mass transfer coefficient.
47. Mixing Parameters for Crystallization Processes
Cooling crystallization of API in 6000 liter reactor.
After investigation it was found that the tip
diameter of the Agitator was damaged and the real
diameter is a 80 % of the reported one.
new.vsm-3107VisiMix_R.vsm3107VisiMix_R
X (v,90) < 250 micronCampaign
195First
325Second
50. Description
• Gas – Liquid reaction in pilot scale ~ 1000 liter
is finished after 4 Hour
• Same in Production 4 Days.
Visimix.Ltd50
51. VisiMix Application
Safe Process Assess
09/06/201551
Developing an innovative way to dramatically
improve the safety of the chemical processes. By:
Mr.Nekhamkin-
17.06.2015 -10:30 am- Hall 9.1, Room: Logos / Genius
52. High Shear Rate at Chemical
Fast Reactions
09/06/201552
An innovative new technology to better utilize processes
for both RSD (Rotor Stator Dispersers) and/or Emulsifiers.
By: Dr. Kokotov- 18.06.2015 -16:40 pm- CMF, Room: Harmonie 5
ApplicationVisiMix
53. Process and Quality Problem
ProcessR-6826
Feed R-Cl
R-NH2 + R’-Cl t-D-R-R’
Impurity
t-L-R-R’
09/06/201553
54. Impurity results at laboratory and in production
SystemvolumeImpeller typeRPMimpurity]%[
Laboratory reactor0.63 lit
rotor stator15,000 rpm0%
3-blade
1,500 rpm0.3%
800 rpm0.6%
100 rpm1.5%
Production
R-6826
2,978 lit
bottom – flat blade
up - turbofoil
140 rpm0.3% - 0.6%
Correlation between shear rates and the impurity concentration
54
55. R’- Cl (liquid)
R- NH2
Working with rotor stator at
laboratory scale
Problem
How to scale up ?
Potential Saving :
MORE than 250 K$
55
57. Calculating shear forces with VisiMix
The required shear rate can not be achieved in the
production reactor
Lab impeller
Rotor statorR-6826
systemImpeller typeRPMimpurity]%[
Turbulent
shear rate
[1/s]
Laboratory
reactor
rotor stator15,000 rpm0%780,000
3-blade
1,500 rpm0.3%32,900
800 rpm0.6%12,900
100 rpm1.5%580
R-6826
bottom – flat blade
up - turbofoil
140 rpm0.3% - 0.6%15,200
09/06/201557
58. Conclusion
Using VisiMix Products support you can
understand better your processes
Reduce dramatically your Scaling up processes and Scaling down
Save a huge amount of Time & Money ($1,000,000 +)
The VisiMix Products are friendly and easy to use with very quick
results.
The VisiMix results are based on a systematic and seriously
experimental checking – and found very reliable.
VisiMix Projects Parameters and Data Base allows you to share and
transfer the data with colleagues in the company.
