Review I

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Review I Particle design using supercritical
fluids Literature and patent survey
Sung-Woo Jeon Dept. of Chemical Eng. Hanyang Univ.
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Abstract
Particle design of supercritical fluids
applications Pharmaceutical, Nutraceutical,
Cosmetic, Specialty chemistry industry RESS
Rapid Expansion of Supercritical
Solutions Consist in solvating the product in the
fluid and rapidly depressurizing this
solution through an adequate nozzle Attractive
due to the absence of organic solvent use Its
application is restricted to products that
pressent a reasonable solubility in supercritical
carbon dioxide(low polarity compounds) GAS or
SAS Gas(or Supercritical fluid)
Anti-Solvent Consist in decreasing the solvent
power of a polar liquid solvent in which the
substrate is dissolved, by saturating it with
carbon dioxide in supercritical
conditions, causing the substrate precipitation
or recrystallization
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Part 1 Rapid expansion of supercritical
solutions (RESS)
Concept Depressurizing this solution through a
heated nozzle into a low pressure chamber in
order to cause an extremely rapid nucleation of
the substrate(s) in form of very small
particles In the precipitation unit, the
supercritical solution is expanded through a
nozzle that must be reheated to avoid plugging by
substrate(s) precipitation The morphology of the
resulting solid material both depends on The
material structure crystalline or amorphous,
composite or pure, The RESS parameters
temperature, pressure drop, distance of impact of
the jet against the surface, dimensions of the
atomization vessel, nozzle geometry,
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RESS Device
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Future Development
RESS is a very attractive process as it is simple
and relatively easy to Implement at least at
small scale when a single nozzle can be
used Extrapolation to a significant production
size requires either a multi-nozzle system or use
of a porous sintered disk through which
pulverization occurs, In both the case, particle
size distribution is not easy to control, and may
be much wider than in the case of a single
nozzle. Particle harvesting is complex The most
important limitation of RESS development lies in
the too low solubility of compounds in
supercritical fluids In most cases, use of a
co-solvent to increase solubility in the fluid is
not feasible
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Part 2 Supercritical anti-solvent and related
process (GAS/SAS)
Concept In this process, the supercritical fluid
is used as an anti-solvent that causes
precipitation of the substrate(s) dissolved
initially in a liquid solvent. The solute is
recrystallized from solution in one of the three
ways. The first method A batch of solution is
expanded several-fold by mixing with a dense gas
in a vessel. Due to the dissolution of the
compressed gas, the expanded solvent has a lower
solvent strength than the pure solvent. The
mixture becomes supersaturated and solute
precipitates in microparticles. This process has
been called gas anti-solvent(GAS) or
supercritical anti-solvent(SAS) recrystallization
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GAS/SAS Device
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Part 2 Supercritical anti-solvent and related
process (GAS/SAS)
The second method Spraying the solution through
an atomization nozzle as fine droplets into
compressed carbon dioxide. The dissolution of
the supercritical fluid into the liquid
droplets is accompanied by a large volume
expansion and, consequently, a reduction in the
liquid solvent power, causing a sharp rise in
the supersaturation within the liquid
mixture, and the consequent formation of small
and uniform particles. This spray process has
been called Aerosol solvent extraction
system(ASES) process
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ASES Device
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Part 2 Supercritical anti-solvent and related
process (GAS/SAS)
The third method In order to achieve smaller
droplet size and intense mixing of supercritical
fluid and solution for increased transfer
rates. Indeed the supercritical fluid is used
both for its chemical properties and as spray
enhancer by mechanical effect A nozzle with two
coaxial passages allows to introduce the
supercritical fluid and a solution of active
substance(s) into the particle formation
vessel where pressure and temperature are
controlled. The high velocity of the
supercritical fluid allows to break up the
solution into very small droplets. The nozzle
design leads to sonic waves development leading
to very tiny particles around 1 ?. This process
has been called solution enhanced dispersion by
supercritical fluids(SEDS).
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SEDS Device
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Part 2 Supercritical anti-solvent and related
process (GAS/SAS)
Three processes are adequate for processing
solids which are difficult to dissolve into
supercritical(RESS is impossible), or are
sensitive to high shear stress such as peptides
or proteins. Addition of a carrier (often a
polymer) to the active solution can lead to the
formation of active substance-loaded micro- /
nano-spheres. Especially for drug delivery
systems, anti-solvent process have bright
future. This process permit to monitor the
properties and composition of the particles with
a great flexibility and for almost any kind of
compounds. Nevertheless, scale-up is presently
foreseen only for high-value specialty material(ph
armaceuticals, cosmetics, superconductors) with
productions ranging from a few kilograms to a few
hundreds kilograms per day.