Another promising field for supercritical fluids is the formation of particles or particle design. Numerous processes have been developed which allow the generation or modification of fine particles with defined particle size distribution in micro- and even in nano scale. Also particles of certain shape (spherical, spicular, etc.) and / or determined morphology (plane, porous, compact, hollow) can be generated.
This new technology is of highest relevance to generate pharmaceutical products and substances. The dosing and release properties of active pharmaceutical ingredients (APIs) are significantly influenced by the particle properties. New drugs with exact and controlled properties will be possible in the near future by using these new processes complementing traditional granulation and spray drying processes.

The following major process platforms have been published:

• RESS (rapid expansion of supercritical solution)
• PGSS (particles from gas saturated solutions)
• GAS (gas anti-solvent crystallisation).

In addition, modified and derived processes are available to manufacture particles or powders with customer-specific characteristics.

The RESS process is used for powdering of substances which are soluble in a supercritical fluid and solid under ambient conditions. The dissolution step can be carried out similar to SFE in an autoclave passed through by the fluid. If the feedstock can be fluidized, the substance can be continuously extracted in a static mixer where the feed is mixed with the supercritical fluid.
After dissolving the extractable substances the supercritical fluid (single-phase) is routed to a nozzle or a pressure control valve where the fluid is depressurized abruptly. Due to the quick depressurization the solubility is decreased immediately causing the precipitation of the dissolved substances as fine particles. With this process particles at micro- to nanoscale can be processed.

In contrast to the RESS process particles formed by the PGSS™ process are formed by spraying of melts (or suspensions) in which the supercritical fluid is dissolved. The feedstock to be micronized is usually solid under ambient conditions. In the presence of a supercritical fluid and elevated pressure the melting temperature of the feedstock materials is reduced (gas induced melting). After melting and dissolving of the supercritical fluid into the melt, the mixture is sprayed via a nozzle or a pressure control valve into a receiver. Due to the abrupt depressurization the solved supercritical fluid escapes and the formed droplets are dispersed into even smaller droplets. In parallel a strong cooling effect (depending on the applied supercritical medium) can be observed (Joule Thomson effect), which causes a quick crystallization of the small droplets. Typical particles formed via PGSS™ process have average particle sizes of some micro-meters.

Similar to the RESS process the dissolving can be realized discontinuously by an autoclave or continuously by a static mixer (or a combination). A modification of the continuous PGSS™ process, the so-called CPCSP process (Continuous Powder Coating Spraying Process) is used to generate particles consisting of more than one component. Due to the low temperatures and small residence time in the static mixer it is also possible to spray reactive components. For example, reactive 2-component powder coating (binder and hardener) can be processed with this process. The components are melted independently and conveyed via pumps or extruders to the static mixer. In the static mixer the substances are mixed and the supercritical fluid is dissolved in the mixture. This mixture is then sprayed in the same manner as for the PGSS™ process via nozzle or pressure control valve. The product will be fine composite powders.

With the GAS Process substances can be micronized which are insoluble in supercritical fluids and which have a poor solubility for supercritical fluids as well. The process principle based on a supplanting crystallization with a supercritical fluid as precipitation agent. For this process the target substance to be micronized is first dissolved in an organic solvent. Then the solvent with the target substance is getting into contact with the supercritical fluid which is acting as anti-solvent. There are many different procedures to combine the two streams. They could be mixed in a static mixer, combined in a nozzle or routed through two or more nozzles directly into the particle collecting vessel. In all cases, the organic solvent is going to be dissolved in the supercritical fluid. As soon as the saturation point is reached, the precipitation of fine particles starts. The formed particles will be in-situ dried by the surrounding supercritical fluid. The standard GAS process allows only a discontinuous operation. Further developed processes such as PCA (Precipitation with Compressed Anti-solvents) or SEDS™ (Solution Enhanced Dispersion by Supercritical Fluids) allow also for a semi-continuous operation.

Currently, the above mentioned processes and derivations are relatively novel in high pressure technology and are mainly used for tests and clinical studies. There are a couple of industrial applications (e.g. powder coating production). In the long term it is expected that many very different products will be processed with these new processes since the advantages are evident. Uhde High Pressure Technologies will keep track of all market developments in this area and provides the required technology and equipment to interested customers.