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supercritical anti solvent
1.
2. In the name of God
Application of supercritical
antisolvent method in
drug encapsulation
Maryam kazemi
Ph.D student of pharmaceutics
Shiraz university of medical sciences
3. The ideal drug delivery method:
Safe
Inert
Comfortable for patient
Biocompatible
Easily administered or removable
High drug loading
Using biodegradable polymers for drug encapsul
ation is one of the best ways to achieved this ide
al method .
4. Supercritical fluid properties:
• SCF is a solvent
• Tempreture & pressure are greater than its
critical T , P.
• It remains as a single phase
5.
6. The best SCF is CO2:
• Non toxic
• Inert
• Low critical T=304 k & low critical P =7.38 MPa.
• Poor solubility for many polymers & drugs /rapid mixing
with the solvent.
• Low viscosity like a gas , Its density similar to the liquid
• Its ability to provide a non degrading and nonoxidizing
environment for sensitive compounds.
7. Limitation of SCF:
Non biocompatibility or toxicity of the
polymers.
Unwanted by product of degradation .
Higher cost
8.
9. The anti solvent application
Bleich and coworkers firstly discovered .
CO2= anti solvent percipitation of the solute
from an organic solvent.
10. The base of this technique is:
• Dissolving a large volume of a SCF by a
n organic solvent .
• Reciprocal miscibility of the SCF CO2 &
an organic solvent
• The low afinity of SCF for solute.
11. Mechanism of SAS
• SC Co2 is pumped in to the high pressure vessel to a
specific pressure .
• Solution (drug+biodegredable polymer+organic solv
ent ) is sprayed in the reactor via a suitable nozzle.
• CO2 diffused in the solvent evaporated in the ga
s phase & the solvent diffuses rapidly from the solut
ion droplet in to the bulk SCF percipitation th
e solute.
12.
13.
14. • Formed particles are collected on a filter
Washed with SCF to remove the resitual solvent
SCF dissolving into the liquid droplet
Evaporation of the organic solvent in the SCF phase
Later percipitate
15. Disadvantages of this method
• Long washing period aggregation particles
To minimize :intensivly mixing SAS & solution
Method : Using Ultra sonic nozzles 10-100 kHZ
Increase mass transfer between SCF & solution
Smaller droplet
16.
17. Effects of the process parameters on the particle size in
the supercritical antisolvent (SAS) process
Effects of pressure:
At higher pressure, obtained smaller particle size. At higher pressu
re, the deforming pressure forces must be increased to break the
droplets into smaller particles. Moreover, particle nucleation and it
s growth are other important factors affecting particle size. Rapid
mass transfer of antisolvent and solvent causes high supersaturati
ons for the solute. High supersaturation results in rapid nucleation
and growth of more than one particle per primary droplet.
At lower pressure, obtained smaller particle size. In a situation abo
ve the critical condition, reduction in pressure is observed to decr
ease the solubility which then results in higher maximum supersat
uration in the reactor; therefore, smaller particles are produced.
Pressure variations have no significant effect on particle size beca
use the free intermolecular volume of the polymer will be occupie
d at the saturation pressure.
18. Effects of temperature
At higher temperature
smaller size and more spherical particles obtained
. But the temperature must be lower than the Tg of
the polymer.
At lower temperature
smaller particle size,obtained due to higher
volatility.
19. Effects of chemical composition of the organic solvent
Particle size decreases with increase in volatility of
the solvent.
Particle size decreased by using a stronger solvent.
Solubility of the biodegradable polymer in the orga
nic solvent must be higher than the solubility of its
drug Contents.
20. Effects of chemical composition of the drug
Lower solubility of the drug in a supercritical
fluid enhances rapid precipitation.
Enhancement of drug lipophilicity reduces the
loading drug efficiency in the SAS process
21. Effects of chemical composition of the biodegr
adable polymer
The crystalline polymer forms smaller particle
size with narrower particle size distribution.
Drug stability in amorphous polymers is higher
than in crystalline polymers
22. Effects of the nozzle geometry
A smaller nozzle diameter reduces the particle size
and produces more spherical-shaped particles.
The effect of the nozzle diameter is not highly
significant.
Co-axial nozzle, is especially designed for
improvement of the morphology.
23. Effects of flow rates of CO2 and liquid phase
Increasing the ratio of CO2 flow rate over the
organic solution flow rate reduces particle size.
24. • References:
• M. Kalani, R. Yunus, Application of supercritical antisolvent
method in drug encapsulation: a review, International Journal of n
anomedicine 6 (2011) 1429‐1442.