Method and apparatus for enhanced size reduction of particles
View Patent ↗The present invention provides methods and apparatus for producing particles via supercritical fluid processing. In one embodiment, the method includes expanding a supercritical fluid plasticized melt across a pressure drop to form solid composite particles that are simultaneously dispersed, foamed and cooled, and milling the solid particles produced to achieve the desired size distribution. In another embodiment, a pressure vessel containing a supercritical fluid plasticized melt is depressurized to form a cooled solid porous mass, which is then milled to obtain solid composite particles.
1. A method of producing solid particles comprising the steps of:
providing a load stock comprising:
an excipient that is a solid at 25° C. and 1 atmosphere pressure; and
optionally, a biologically active substance;
contacting the load stock with a supercritical fluid in a pressure vessel that is pressurized and heated to maintain said fluid supercritical, and to form a melt;
depressurizing the pressure vessel to transform the melt in the pressure vessel into a solid porous mass that is cooled to a temperature below 25° C.; and
milling the solid porous mass to obtain solid particles.
2. The method according to claim 1 wherein the solid porous mass is milled before the temperature of the solid porous mass is permitted to rise to 25° C.
3. The method according to claim 1 wherein subsequent to the milling step the solid particles have an average particle size of from about 0.1 to about 500 micrometers (μm).
4. The method according to claim 1 wherein the excipient is a polymer selected from the group consisting of polysaccharides, polyesters, polyethers, polyanhydrides, polyglycolides, polylactic acids, polycaprolactones, polyethylene glycols and polypeptides.
5. The method according to claim 1 wherein the supercritical fluid is selected from the group consisting of carbon dioxide, water, nitrous oxide, dimethylether, straight chain or branched C 1 -C 6 -alkanes, alkenes, alcohols, ethane, propane, fluoroform, chlorotrifluoromethane, chlorodiflueromethane, propylene, ammonia and combinations thereof.
6. The method according to claim 1 wherein the supercritical fluid is carbon dioxide.