MICRONIZATION AND ENCAPSULATION

WITH SUPERCRITICAL CARBON DIOXIDE

Seminar on
M.Tech. Project (1st Stage)
by
Rajarshi Guha
Roll No. 07302009

Guide: Prof. Madhu Vinjamur

Chemical Engineering
Department
IIT Bombay
 WHAT IS SUPER CRITICAL FLUID (SCF) ?

 A fluid which is above its critical point is called Supercritical fluid.

 CO2 has its critical point at 31.1˚C and 73.8 bar (7.48 MPa).

 Transport properties of SCFs are in between liquid and gas.

 SCFs POSSESS BOTH LIQUID AND GAS LIKE
PROPERTIES - PROPERTY TUNING

 SCF has liquid like densities

- good dissolution power.

 Gas like diffusivities

- mass transfer gets faster.

 Dissolving power increases with increase in

pressure (density) .

 Decreasing pressure decreases solubility

- solute precipitates out. Fig. Solubility of Naphthalene in SC CO2 at 45 ˚C

Phases Density Viscosity Diffusivity

(Kg/m³) (cP) (mm/s²)
Gases 1 0.01 1-10
SCFs 100-1000 0.05-0.1 0.01-0.1
Liquids 1000 0.5-1.0 0.001
 APPLICATIONS OF SCF ASSISTED
PRECIPITATIONS
Membrane
and
Coating
Particle Applications
Micronization
Inorganic
and
Organic
Chemical Powder
Particle Systems Formed
Micronization Experimented Chemical
and Using SCF precipitation Production
Encapsulation

Polymer Semiconductor
Particle Applications
Production
DIFFERENT PROCESSES - NON SAS
(SUPERCRITICAL ANTI-SOLVENT)

NON SAS

RESS PGSS
Rapid Expansion of
Particles from Gas Saturated Solutions
Supercritical solutions
 BASIC NON SAS PROCESS
 Two vessels are used,

- one for solute dissolution

into SC CO2

- another for depressurization

and precipitation through a
nozzle.

 No additional solvent is used.

 The solute should be soluble

in SCF (RESS).

 SCF should be soluble in

solute (PGSS).
 DIFFERENT PROCESSES- SAS

SAS
PROCESSES

SASEM GAS PCA SEDS ASES SAA

 BASIC SAS PROCESS
 One chamber process,

- SC CO2 comes through preheater

and CO2 pump

- solution through solvent pump

and nozzle.

 Solution is dispersed into SCF.

 Precipitation occurs due to anti solvent

effect of SCF.

 The organic solvent should be soluble

in SCF.

 Solute should be insoluble in SCF.

 SAS PROCESS MECHANISM
TWO COMPONENT (SOLVENT- SC CO2)

• CO2 diffusion into droplet.

2. Solvent evaporation along with CO2 diffusion.

3. Swelling of droplets or shrinking of droplets.

4. Swelling to shrinking due to back diffusion of CO2 along with

solvent evaporation.
 SAS PROCESS MECHANISM
THREE COMPONENT (SOLVENT-SOLUTE- SC CO2)

 Fast SC CO2 diffusion into and out of the droplet - rapid droplet saturation.

 SC CO2 diffusion creates an empty shell or balloon structure.

 The balloon bursts into small viscous droplets containing particles and
polymer (solute).

 Further solvent evaporation and extraction by SCF - glass transition of the

polymer.

 Supersaturation > Nucleation > precipitation of polymer on the surface of the

particles.
 DIFFERENT PARAMETERS
Parameters of micronization and
encapsulation

1. Temperature

2. Operating pressure

3. Solute concentration

4. Solute (polymer) molecular weight and Solute

weight fraction

5. Solution flow rate and Ratio of carbon dioxide

to solution flow rate

6. Nozzle Diameter

7. Nature of solvent

8. Density of SCF (CO2)

9. Presence of surfactant
 TEMPERATURE INCREASES PARTICLE SIZE

Particle size
increases

Temperature
increases

In polymer
Encapsulation Particle
Particles Sphericity
Get increases
Agglomerated

Pressure is dominant parameter than temperature

 PRESSURE DECREASES PARTICLE SIZE

Particle
size
decreases

Pressure
increases

Plasticization Particles
Of polymer Deviate
Increases From
And Spherical
Agglomeration shape

Concentration is another important parameter

 CONCENTRATION INCREASES PARTICLE SIZE

Nucleation
decreases

Concentration
increases

Mean
Particle
Particle
Growth
Size
increases
Increases

Polymer concentration is important in

encapsulation or polymer particle production
 POLYMER CONCENTRATION RESULTS IN AGGLOMERATION

 Increase in polymer weight fraction

- Agglomeration during
encapsulation
- Encapsulation Efficiency (EE)
increases

 It has been experimented 1:1 polymer

: solute maintains both agglomeration
and EE in check¹.

 In the figure, the 1st one is for 1:4 and

2nd one is for 1:6 ratio .

 Temperature and Pressure should be

higher for higher mol. wt. polymer.

¹Wang et al., 2003. J. Supercrit. Fluids. 28:85-99.

 OTHER PARAMETERS CHANGES INITIAL
DROPLET SIZE
 Flow rate ratio (G/L) increase
- Decreases initial drop size
- Narrows Particle Size
Distribution².

 Nozzle diameter increase

- increases initial drop diameter.

 Nature of solvent
- Affects liquid mass transfer
coefficients.

 Density gives the same effect as

pressure.

 Surfactants
- reduces interfacial tension
- reduces initial drop diameter
- increases agglomeration.

² Kim et al., 2003. J. Powder. Tech. 177:64-70.

 MICRONIZATION EXPERIMENTS
Drug Drug Solvent Temperature Pressure CO2 Solution CO2/Solution
Sample Conc. (˚C) (bar) Flow-rate Flow rate flow rate ratio
(% w/v) (Kg/hr) (gm/min) (wt/wt)
in gm/ml

R1 1 MeOH 60 100 35 8.89 66

R1 2 MeOH 60 140 35 8.89 66
R1 4 MeOH 60 100 35 8.89 66
R2 5 Acetone 60 100 52 6.67 130
R2 2 Acetone 60 100 52 10 87
R2 1 Acetone 60 100 40 8.89 75
R2 4 Acetone 60 100 50 10.375 80.32
R3 0.5 MeOH 60 100 35 8.84 66
R4 3 Acetone 60 100 40 9.11 73.17
R4 3 Acetone 60 100 40 7.45 89.43
R4 3 Acetone 60 100 44 7.45 98.37
 EXPERIMENTAL RESULTS
Drug Drug Yield Conc. (mg/ml) Polydispersity Effective Mean
Sample Conc. (%Y) DLS analysis diameter Diameter
(% w/v) (μm) (μm)
(gm/ml)
R1 1 11 1.28 0.524 23.9 6.6
R1 2 0 - - - -
R1 4 2.5 - - - -
R2 5 32 0.25 0.570 20.7 4.9
R2 2 25 0.35 0.460 17.2 0.57
R2 1 25 0.36 0.382 22.3 9.8
R2 4 20 - - - -
R3 0.5 0 - - - -
R4 3 26.67 - - - -
R4 3 21.67 - - - -
R4 3 40 - - - -
 DYNAMIC LIGHT SCATTERING ANALYSIS

Intensity v/s Diameter for (R2,5%) Number v/s Diameter for (R2,5%)

Intensity v/s Diameter for (R2,2%) Number v/s Diameter for (R2,2%)

Intensity v/s Diameter for (R2,1%) Number v/s Diameter for (R2,1%)
CONCLUSIONS

1. The use of SC CO2 as a green solvent is emerging

out rapidly.

2. Various SAS and non SAS processes have been

designed to produce particles of controlled size,
shape and surface properties.

 In the first stage only micronization experiments

have been performed to understand
- basic process parameters.
- plant operation.