Method and apparatus for supercritical fluid assisted particle production
View Patent ↗The present invention provides an apparatus and methods of producing particles that include a polymer, a wax and/or lipid and, optionally, a biologically active substance. In accordance with the methods of the invention, a load stock including a polymer, a wax and/or a lipid that is a solid at standard temperature and pressure and, optionally, a biologically active substance is provided. The load stock is contacted with a supercritical fluid to form a melt. The melt is contacted with a polar solvent under suitable conditions to form an emulsion. The emulsion is expanded across a pressure drop to form solid particles that include the load stock. The methods and apparatus facilitate the production of very small particles that have a narrow particle size distribution.
1. A method of producing solid particles comprising the steps of:
providing a load stock comprising:
at least one material that is a solid at standard temperature and pressure selected from the group consisting of polysaccharides, polyesters, polyethers, polyanhydrides, polyglycolide, polylactic acid, polycaprolactone, polyethylene glycol, polypeptides, waxes and glycerides; and
optionally, a biologically active substance;
contacting the load stock with a supercritical fluid to form a melt;
contacting the melt with a polar solvent to form an emulsion, the emulsion having a discontinuous phase comprising the melt and a continuous phase comprising the polar solvent; and
expanding the emulsion across a pressure drop to form solid particles comprising the load stock.
2. The method according to claim 1 wherein the emulsion is expanded through a heated nozzle.
3. The method according to claim 1 wherein the solid particles are collected in an expansion vessel.
4. The method according to claim 3 wherein a stream of inert gas flows through the expansion vessel to remove the expanded supercritical fluid.
5. The method according to claim 1 further comprising adjusting a rate of expansion of the emulsion across the pressure drop to control the morphology and/or size of the solid particles.
6. The method according to claim 1 wherein the supercritical fluid is carbon dioxide.
7. The method according to claim 1 wherein the polar solvent is selected from the group consisting of water and alcohol.
8. The method according to claim 1 wherein a surfactant is added to the polar solvent before the polar solvent is contacted with the melt.