Particles from supercritical fluid extraction of emulsion
View Patent ↗A method of producing microparticles and nanoparticles of a solute via the extraction of solvent, having the solute dissolved therein, from an emulsion using a supercritical fluid. The solute to be precipitated is dissolved in the solvent to form a solution, and the solution is dispersed in an immiscible or partially miscible liquid to form an emulsion. The particles are produced via the extraction of the solvent from the emulsion using the supercritical fluid. The process can produce an aqueous suspension of particles that are substantially insoluble in water, and the solvents used in the process to form the emulsion initially can be recovered and recycled.
1. A method of producing an aqueous suspension of particles, comprising:
contacting an emulsion with a supercritical fluid, the emulsion having a continuous aqueous phase and a discontinous non-aqueous phase, the discontinuous non-aqueous phase comprising an organic solvent having a solute dissolved therein, the solute being generally insoluble in the continuous aqueous phase, and the organic solvent being soluble in the supercritical fluid; and
extracting the organic solvent from the discontinous non-aqueous phase of the emulsion and into the supercritical fluid while the supercritical fluid is maintained as a supercritical phase to precipitate particles comprising the solute into the continuous aqueous phase and thereby form an aqueous suspension of particles.
2. The method as defined in claim 1 wherein the solute comprises a biologically active material or a drug.
3. The method as defined in claim 1 wherein the solute comprises a polymer.
4. The method as defined in claim 3 wherein the polymer is a biodegradable polymer.
5. The method as defined in claim 1 wherein wherein the emulsion and the supercritical fluid are separately fed into and contacted together in an extraction chamber, wherein the aqueous suspension of particles comprising the solute is removed from the extraction chamber at about the same rate as the emulsion is fed into the extraction chamber, and wherein supercritical fluid bearing the organic solvent extracted from the emulsion is removed from the extraction chamber at about the same rate as the supercritical fluid is fed into the extraction chamber.
6. The method as defined in claim 1 wherein the particles have an average diameter of from about 0.1 nanometers to about 1.0 millimeter.
7. The method as defined in claim 6 wherein the particles have an average diameter of from about 0.1 micrometers to about 400 micrometers.
8. The method as defined in claim 7 wherein the particles have an average diameter of from about 1 nanometer to about 500 nanometers.
9. The method as defined in claim 1 wherein the emulsion further comprises a surfactant.
10. The method as defined in claim 1 wherein the supercritical fluid comprises carbon dioxide.
11. The method as defined in claim 1 wherein the solute is selected from the group consisting of medicinal agents, nutritional materials, proteins, peptides, alkaloids, alkyloids, animal and/or plant extracts, antigens, nucleic acids, antibiotics, vitamins, lipids, polymers, polymer precursors, pigments, toxins, insecticides, viral materials, diagnostic aids, agricultural chemicals, dyes, explosives, paints, cosmetics, enzymes, and catalysts.
12. The method as defined in claim 1 wherein the particles are substantially spherical.
13. The method as defined in claim 1 further comprising the step of selecting a concentration of the solute in the organic solvent to obtain a desired particle size, wherein an increase in the solute concentration results in an increase in the particle size, and a decrease the solute concentration results in a decrease in the particle size.
14. The method as defined in claim 1 further comprising the step of selecting a concentration of the discontinuous non-aqueous phase in the continuous aqueous phase of the emulsion to obtain a desired particle size, wherein an increase in the concentration of the of the discontinuous non-aqueous phase in the emulsion results in an increase in the particle size, and a decrease the concentration of the of the discontinuous non-aqueous phase in the emulsion results in a decrease in the particle size.
15. The method as defined in claim 1 further comprising the step of injecting the emulsion into the supercritical fluid to form emulsion droplets, the droplets containing portions of the continuous aqueous phase and the discontinuous non-aqueous phase, wherein the particles are precipitated and suspended in the continuous aqueous phase in the droplets after the step of extracting the organic solvent from the discontinuous non-aqueous phase.
16. The method as defined in claim 15 further comprising the step of selecting a droplet size of the emulsion to obtain a desired particle size, wherein an increase in the droplet size results in an increase in the particle size, and a decrease the droplet size results in a decrease in the particle size.
17. The method as defined in claim 15 wherein the emulsion is injected through a nozzle such that the emulsion is sprayed into a volume of the supercritical fluid, and the nozzle is a capillary nozzle, a coaxial nozzle or an ultrasonic nozzle.
18. The method defined in claim 15 wherein the emulsion droplets are contacted with the supercritical fluid in a mixer to increase the contact area between the emulsion droplets and the supercritical fluid, the mixer being a vibrating surface or a propeller mixer that increases the mass transfer rate of the organic solvent from the emulsion droplets to the supercritical fluid.
19. The method as defined in claim 1 further comprising the steps of filtering the particles comprising the solute from the aqueous suspension to form a concentrated cake of particles, and freeze drying the cake to obtain dry particles.
20. The method as defined in claim 1 wherein the supercritical fluid is is selected from the group consisting of carbon dioxide, water, trifluoro methane, nitrous oxide, dimethylether, straight chain or branched C1–C6-alkane, alkene, alcohol, and combinations thereof.