PARTICLE MICRONIZATION AND

ENCAPSULATION WITH SUPERCRITICAL

CARBON DIOXIDE

M.Tech. Project 2nd Stage

Presentation
by
Rajarshi Guha

Chemical Engineering
Department
IIT Bombay
 Supercritical Anti-Solvent (SAS) Process

Droplet formation in SC CO2

phase through nozzle CO2 dissolution in the
droplet

Simultaneous CO2 dissolution

and Solvent evaporation

Drop size Drop size

increases decreases

Rapid solute supersaturation, nucleation, growth and particle precipitation occur

 Effect of CO2 to solvent mass flow rate ratio
and density on initial drop size
Simulated system is two component DCM-SC CO2 at T=333 K and P= 75 bar
-7 -6
x 10 x 10
3.05 7.2

7
3

6.8
Initial drop diameter in micrometer

Initial drop diameter in micrometer

2.95
6.6

2.9
6.4

2.85 6.2

6
2.8

5.8
2.75
5.6

2.7 5.4
0 50 100 150 100 200 300 400 500 600 700 800
CO2 to solution mass flow rate ratio CO2 density in (Kg/m3)

Flow rate ratio increases……

CO2 density increases…..
Initial drop diameter decreases
Initial drop diameter decreases
Decrement is maximum beyond (Flow rate ratio is kept 80)
ratio 20

Ratio above 100 does not give

considerable diameter decrease
 Mass and Heat Transfer Modeling
DG
KG  (2  0.00187 N Re 0.779 N Sc 0.546 (dg 0.333 DG 0.667 )0.116 )
d
N G  K G G y2i / M CO2 -Solvent flux to SC CO2

4 DL
KL   tc

N L  K L  L ( x1i  x1 ) / M sol -CO2 flux to solvent (droplet)

NTotal  N o  ( N L  N G ) d t 2
-Net mole transferred
into droplet
o 1 x1
DL  ( DL ) o
( DG ) x1

( hdissolution N L  hevaporation N G )t 2K

Tdrop  T  hL 
hL d
6 NTotal
d [ ]1/ 3 - Drop diameter
 (  L / M mixture )
 Droplet size evolution - Two/ Three/ Four
x 10
-4
component systems -4
1.8 x 10
3.5

1.6
3
1.4

2.5
1.2
diameter(m)

diameter(m)
1 2

SC CO2-DCM system Acetone-Cholesterol- CO2

0.8
1.5
system
0.6 T = 333 K P = 75 bar
1
T = 313 K P = 82.3 bar
0.4

0.2 0.5
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s) x 10
-4 time(s)
1.6

1.5

1.4
Initial droplet swelling followed by
1.3
droplet evaporation
1.2
diameter(m)

1.1
4 component droplet size decrement 1
DCM-Cholesterol-
is faster than two component system PLLA- SC CO2 system
0.9

0.8
T = 318 K P = 90 bar
0.7

0.6
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s)
 Effect of solvents on droplet Size
evolution
-4 -4
x 10 x 10
3.5 5.5

DCM – SC CO2 system 5 Acetone – SC CO2 system

3
T = 318 K P = 80 bar T = 318 K P = 80 bar
4.5
2.5
diameter(m)

diameter(m)
4
2
3.5

1.5
3

1
2.5

0.5 2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 0.5 1 1.5 2 2.5 3
time(s) time(s)

DCM droplet evaporates at around 1 second whereas Acetone droplet

evaporates at around 3 seconds

Higher volatility of DCM solvent helps in faster evaporation of droplet

 Droplet decelerates during evaporation
2.5 3

2.5
2
SC CO2-DCM system Acetone-Cholesterol-
2
CO2 system
1.5 T = 333 K P = 75 bar

velocity(m/s)
velocity(m/s)

1.5
T = 313 K P = 82.3 bar

1
1

0.5
0.5

0 0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s) time(s)
1

0.9

Drop velocity decreases continuously 0.8

DCM-Cholesterol- PLLA- SC
0.7 CO2 system
Initially droplet decelerates at a faster rate 0.6

velocity(m/s) T = 318 K P = 90 bar

during droplet swelling due to increased drag and 0.5

buoyancy 0.4

0.3

Then decelerates at a slower rate during droplet 0.2

evaporation due to decreased drag and buoyancy 0.1

0
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s)
 1
CO2 diffusion into droplet 1

0.9 0.9
2 component system
0.8 0.8

0.7 0.7
3 component system
mole fraction(CO2)

mole fraction(CO2)
0.6 0.6

0.5
Mole fraction stays constant 0.5 Mole fraction reaches equilibrium
0.4 for longer times during 0.4 fast followed by slower increase
0.3 evaporation 0.3

0.2
0.2

0.1
0.1

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s)
time(s)
1

0.9

0.8

0.7
mole fraction(CO2)

0.6
4 component system
0.5

0.4 Equilibrium attainment is faster

0.3 than 3 component case
0.2

0.1

0
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s)
 Drop (mixture) concentration evolution
2500 700

2 Component system 680

2000 3 Component system
Mixture conc. becomes
conc of CO2-DCM mix. (gm/lit)

660

nearly zero Mixture conc. is decreasing

conc of CO2-Acetone
1500
up to the level of

mix. (gm/lit)
as the solvent 640

evaporates completely supersaturation

1000 620

600
500

580

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 560
time(s) 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s)
1300

1200
4 Component System
1100
conc of CO2-DCM mix. (gm/lit)

1000
Mixture conc. decreases up to
900
a certain value
until the solution gets
800
supersaturated
700

600

500

400
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s)
 Total and CO2 moles inside droplet
-11 -11
x 10 x 10
6 3

2 Component DCM-SC CO2

System
4 2
Total moles

CO2 moles
(kmols)

(kmols)
2 1

0 0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
time(s)

 The mole fraction profiles follow the drop diameter pattern

 3 and 4 component mole profiles are similar to 2 component system

 Temperature evolution
346 313.05

344
2 component 313.04 3 component system
342
system

Temperature of droplet(K)
Temperature of droplet(K)

340 313.03

338
313.02
336 Profile is similar to Temperature hardly
334
diameter profile 313.01 changes, increases
by 0.04 K and then
Temperature increases to 345 K
332 decreases by 0.04 K
from 333 K 313
heat of evaporation of
330
Then decreases to 329 K acetone > heat of dissolution of CO2
328 312.99
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s) 330 time(s)

328
4 component system
Temperature of droplet(K)

326

324

322 Similar to 2 component

system except shrinking
320 regime is curved

318 Temperature increases to 329 K

from 318 K then decreases back to 318 K
316
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s)
 5.5
x 10
-4
Droplet evaporation with height
5
2 component drop takes larger height
to evaporate
4.5

Drop diameter becomes maximum

diameter(m)

4
at the middle of the evaporation height
3.5 for multi-component systems and
then shrinks as solvent evaporation starts
3

2.5 2 component Acetone-SC CO2 These profiles are important to calculate

vessel L/D
2
0 0.5 1 1.5 2 2.5 3 3.5 4
height/distance from top(m)
-4 -4
x 10 x 10
3.5 1.6

1.5
3
1.4

1.3
2.5
1.2
diameter(m)
diameter(m)

2 1.1

3 component Cholesterol- 4 component Cholesterol-

1
1.5 Acetone-SC CO2 PLLA-DCM-SC CO2
0.9

0.8
1
0.7

0.5 0.6
0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
height/distance from top(m) height/distance from top(m)
 Solute supersaturation with time
8

6 High supersaturation indicates homogeneous

5
nucleation
ln (Supersaturation)

4
Smaller time frame with high supersaturation
3 indicates micronization
2
3 component –cholesterol
1
supersaturation (0.005 mole
0 fraction cholesterol in acetone)
-1
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
time(s)
6 9

8
4
7 0.64 gm cholesterol and 1.33
gm PLLA in 200 ml DCM
Supersaturation of cholesterol

Supersaturation of PLLA
2
5

0 4

3
-2 4 component –cholesterol
2
supersaturation 4 component –PLLA
1
-4 (0.00533 mole fraction supersaturation
cholesterol in DCM) 0
(0.00000431 PLLA in DCM)
-6 -1
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s) time(s)
 x 10
-3
Solute solubility profiles
8

7
3 component
cholesterol solubility profile
Cholesterol solubility mole fraction

4 For 4 component system early

solubility reduction of cholesterol
3
than PLLA indicates encapsulation
2

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
-6
CO2 mole fraction x 10
0.05 6

0.045
5
0.04
Cholesterol solubility mole fraction

4 component 4 component
0.035
cholesterol solubility profile sol. mol. fr. of PLLA
4
PLLA solubility profile
0.03

0.025 3

0.02
2
0.015

0.01
1
0.005

0 0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
CO2 mole fraction (4C System) mole fr. CO2 (4 component system)
 Effect of polymer concentration
0.5 gm cholesterol and 2.5 gm PLLA in 200 ml DCM
6
10

9
4
8
Higher polymer fraction
results in high
Supersaturation of cholesterol

2 7

Supersaturation of PLLA
6
supersaturation
0
5
for both the solutes
4
-2
3

2
-4

-6 0
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s) time(s)

0.5 gm cholesterol and 1 gm PLLA in 200 ml DCM

2 9

8
0
Lower polymer fraction 7
Lower polymer fraction
reduces cholesterol keeps almost the same
Supersaturation of cholesterol

-2 6
supersaturation polymer supersaturation
-4 Supersaturation of PLLA 5

4
like higher fraction
-6
3

-8 2

1
-10
0

-12 -1
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
time(s) time(s)
 Conclusions
 Droplet simulation gives an insight about the process and parameters.

 Proper prediction about the process parameters like temperature,

pressure and feed concentration can be achieved prior to experiment.

 Simulation results can be used to design SAS plant.

 Future Work

 Experiments on DCM-Cholesterol-PLLA-SC CO2 system with

optimized process parameters by process simulation and detail
analysis of experimental results.

 Experiments on Zinc Acetate (ZnAc) - Poly Ethylene Glycol

(PEG) - SC CO2 – Acetone/ DMSO solvent system by SAS and
PPRGEL process to compare particle characteristics and yield.