Supercritical Making Nanoparticle System
Nanoparticles with Supercritical Fluids, Co2 extraction system
Supercritical making nanoparticle (supercritical crystallization) preparation technology is a new method for preparing ultrafine particles.
Compared with the traditional method, supercritical making nanoparticle (supercritical crystallization) is mild in preparation conditions, does not need to be in contact with a solvent, and has a small particle size and uniform distribution, and is particularly suitable for miniaturization of heat-sensitive and easily oxidizable biologically active substances.
The development of ultrafine particles, especially nano-sized particles, has become a hot field in the current high-tech, and has been widely used in materials, chemicals, light industry, metallurgy, electronics, biomedicine and other fields. There are various methods for preparing ultrafine particles.
Supercritical fluid deposition technology is a new technology under investigation.
In the case of supercritical conditions, lowering the pressure can result in supersaturation and a high saturation rate can be achieved, and solid solutes can be crystallized from the supercritical solution. Since this process is carried out in a quasi-homogeneous medium, the crystallization process can be controlled more accurately.
It can be seen that solid deposition from supercritical solutions is a promising new technology that produces fine particles with a small average particle size and can control the size distribution.
Supercritical fluid precipitation processes can produce a narrow particle size distribution. A gas becomes a supercritical fluid above a critical point, at a certain temperature and pressure. SCFs possess properties that are intermediate between liquids and gases. Generally CO is used because of its relatively mild supercritical conditions.
Moreover, it is inexpensive, non-toxic, non-corrosive and not explosive or flammable.
A possible refinement of the supercritical fluid technology involves the stirring of surfactants with an aqueous metal salt solution in supercritical CO. This process leads to the formation of microemulsions, which can be viewed as potential nanoreactors for synthesizing extremely homogeneous nanoparticles
RESS (Rapid Expansion of Supercritical Solutions)
The supercritical fluid is used as a solvent for the drug, and the solubility of the drug in the high-pressure supercritical fluid is required to be large. When the supercritical fluid in which the drug is dissolved is suddenly reduced to the normal pressure room temperature, the state of the drug is restored to the normal gas state, and the solubility of the drug is drastically decreased. The dissolved drug is rapidly nucleated and precipitated in a supersaturated state to form fine particles. Studies have shown that the main factors affecting the physical properties such as particle size and morphology include the solubility of the drug in the supercritical fluid, the nozzle diameter, the pressure temperature of the particle forming kettle, the decompression and expansion phase transition path, and nozzle clogging and particle polymerization.
RESS consists of the saturation of the supercritical fluid with a solid substrate; then, the depressurization of the solution through a heated nozzle into a low pressure chamber produces a rapid nucleation of the substrate in form of very small particles that are collected from the gaseous stream. The morphology of the resulting solid material, crystalline or amorphous, depends on the chemical structure of the material and on the RESS parameters(temperature, pressure drop, impact distance of the jet against a surface, nozzle geometry, etc.) The very fast release of the solute in the gaseous medium should assure the production of very small particles. This process is particularly attractive due to the absence of organic solvents.
GAS (Supercritical Fluid Anti-Solvent)
The use of a supercritical fluid as an anti-solvent for a drug requires that the drug be insoluble or have a low solubility in the supercritical fluid. The drug is first dissolved in a general organic solvent (the solvent must be dissolved in the supercritical fluid) and then mixed with the supercritical fluid. When the solvent density is drastically reduced, the solvency of the drug is rapidly lowered, and the drug solution is actually supersaturated, resulting in crystallization of particles. Studies have shown that the main factors affecting the physical properties such as particle size and morphology include the solubility of the drug in organic solvents, the degree of insolubility of the drug in the supercritical fluid, the degree of swelling of the drug in the organic solvent, and the ratio of the organic solvent to the supercritical fluid. The pressure temperature of the particle forming kettle, the phase transition path of the particle nucleation process, and the like.
Here the compound is dissolved in an organic solvent, a supercritical fluid is introduced, expanding the volume and lowering the solvents solvent strength causing the compound to precipitate under controlled conditions of particle formation.
GAS has been proposed using various acronyms; but, the process is substantially the same in all the cases. A liquid solution contains the solute to be micronized; at the process conditions, the supercritical fluid should be completely miscible with the liquid solvent; whereas, the solute should be insoluble in the SCF. Therefore, contacting the liquid solution with the SCF induces the formation of a solution, producing super-saturation and precipitation of the solute.
ASES (Aerosol Solvent Extraction System)
ASES process involves jet break-up of the drug/polymer solution as fine droplets into compressed carbon dioxide through an atomization nozzle. It is expected that the particle size/morphology and crystallinity of solid dispersion could be controlled by changing temperature/pressure during ASES process, leading to improve solubility and dissolution rate.
SEDS (Solution Enhanced Dispersion by Supercritical Fluids)
The general principle is the same as that for SAS, AESE process. The essential difference is related to the way of introducing the different phases ; in SEDS, a coaxial nozzle is used.
PGSS (Particles from Gas Saturated Solutions)
Using the PGSS process for the production of composites, a shell material is filled in and molten in vessel. The shell material is premixed with the emulsifier. The liquid is filled in vessel. The materials are pressurized and dosed to a mixing system using two high pressure pumps. In the mixing system the two substances are mixed and homogenized. A supercritical fluid (CO2) is added and partly dissolved in the formed emulsion. In the mixing system micro droplets of the core material are dispersed in the liquefied shell material. The dispersion is expanded to ambient pressure through a nozzle into a spray tower. Fine droplets are formed by expansion. Simultaneously the drops are cooled by the expanding gas (Joule-Thomson effect). The shell material solidifies and forms a cover around the micro liquid drops, generating a powderous composite.