Chemistry Reference
In-Depth Information
Fig. 5 Change of the phase system in the GAS process.
26
The addition of the anti-solvent
alters the phase system from that of a single homogeneous phase to a two-phase.
Reproduced from Journal of Supercritical Fluids, (2005), 34, page 290 with permission of
Elsevier.
system, as shown in Fig. 5. The result of this phase separation is the for-
mation of solid product and the expansion of the new combined solvent/
anti-solvent phase. The system then requires washing with the dense gas to
remove any remaining solvent that could cause re-dissolution.
The GAS process, unlike the semi-continuous SAS process, does not
require a system that is above the critical point of the mixture, and hence
only requires near critical conditions. GAS is a dynamic process that is
clearly not at steady state. The morphology and structure of materials
produced by the process depends primarily on nucleation rate and
growth rate of the product. Factors that influence the nucleation and
growth rates are the degree of solubility between the anti-solvent
and solvent, the rate of transition from a single phase system to a two
phase system and the maximum degree of supersaturation. The solubility
of the anti-solvent is dependent on its density, so pressure and tempera-
ture of the system are also crucial variables. The maximum attainable
supersaturation is dictated by the concentration of solute in the starting
solution and the mole fraction of anti-solvent in the expanded phase,
which is in turn related to the temperature and pressure of the system.
The rate of pressurisation of the system, and consequently the
expansion rate that drives the single solute-solvent phase into a two
phase system, has a significant influence on the structure of the
precipitated materials. Foster and c-workers showed that using studies of
the precipitation of copper derived anti-inflammatory drugs, that slow
pressurisation rates reduce nucleation rates and can yield crystalline
phases, whilst faster rates produce amorphous material due to the higher
nucleation rate.
45
Reverchon and co-workers have also concluded, by
studying the precipitation of poly vinyl alcohol, that the morphology and
the particle size distribution are strongly influenced by the pressurisation
rate and the geometry of the precipitation vessel.
46
The supercritical anti-solvent process (SAS) is also known as aerosol
solvent extraction system (ASES) and precipitation with a compressed
anti-solvent (PCA) process. SAS differs from GAS as it is a steady state
