Lyophilization method and apparatus for producing particles
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
B01D-009/04
B01D-043/00
B01D-037/00
C02F-001/22
F26B-005/06
출원번호
US-0434435
(2003-05-08)
발명자
/ 주소
Shekunov, Boris Y.
Chattopadhyay, Pratibhash
Seitzinger, Jeffrey S.
출원인 / 주소
Ferro Corporation
대리인 / 주소
Rankin, Hill, Porter &
인용정보
피인용 횟수 :
37인용 특허 :
29
초록▼
A method and apparatus for producing particles, the apparatus includes a solution source that supplies a solution, and a fluid source that supplies a fluid. The solution includes a solvent and a solute. A mixer receives the solution and the fluid from the sources, and mixes the solution and the flui
A method and apparatus for producing particles, the apparatus includes a solution source that supplies a solution, and a fluid source that supplies a fluid. The solution includes a solvent and a solute. A mixer receives the solution and the fluid from the sources, and mixes the solution and the fluid together to form a mixture. The mixture is supplied from the mixer to an expansion assembly at first pressure. The expansion assembly sprays and expands the mixture substantially simultaneously to form frozen droplets, and preferably to form a low-density powder of frozen droplets. A freeze-dry apparatus sublimes the solvent from the particles. A high mass-transfer rate and a uniform open-structure of the powder bed enhances the freeze-drying process. Solid particles having a controlled size distribution are obtained. The particles preferably have a hollow or porous morphology suitable for differing drug delivery applications to include aerosol formulations.
대표청구항▼
1. An apparatus for producing particles comprising:a solution source for supplying a solution comprising a solvent and a solute; a supercritical fluid source for supplying a supercritical fluid; a mixer in fluid communication with the solution source and the supercritical fluid source for mixing the
1. An apparatus for producing particles comprising:a solution source for supplying a solution comprising a solvent and a solute; a supercritical fluid source for supplying a supercritical fluid; a mixer in fluid communication with the solution source and the supercritical fluid source for mixing the solution and the supercritical fluid together to form a mixture, and for maintaining the mixture at a first pressure sufficiently high so as to maintain the supercritical fluid in a supercritical state; an expansion assembly comprising an expansion vessel having an inner surface defining an expansion chamber that is in fluid communication with the mixer for spraying the mixture across a pressure drop to form mixture droplets, the mixture droplets comprising the solute and frozen solvent; a thermostat that is operable to control a temperature in the expansion chamber to be below the solution freezing temperature; and a freeze-dry apparatus that is in communication with the expansion assembly for subliming the frozen solvent, and thereby removing the frozen solvent from the solute, whereby solute particles are produced that are generally free of the solvent. 2. The apparatus as defined in claim 1 wherein the expansion assembly receives the mixture from the mixer at the first pressure, and sprays the mixture at a second, lower pressure such that a portion of the fluid expands in response to a change from the first pressure to the second lower pressure, the expansion of the fluid portion reducing a temperature of the mixture so as to be below a freezing point of the solution.3. The apparatus as defined in claim 1 wherein the solvent is selected from the group consisting of water, alcohol, toluene, ethyl acetate, methyl chloride, methylene chloride, dimethyl sulfoxide (DMSO), dimethyl formamide (DMF), or other organic or inorganic solvents.4. The apparatus as defined in claim 1 wherein the solute is selected from the group consisting of polymer, filler, disintegrant, binder, solubilizer, excipient, surfactant, and combinations thereof.5. The apparatus as defined in claim 4 wherein the solute is a polymer selected from the group consisting of polysaccharide, polyester, polyether, polyanhydride, polyglycolide (PLGA), polylactic acid (PLA), polycaprolactone (PCL), polyethylene glycol (PEG), or polypeptide.6. The apparatus as defined in claim 1 wherein the solute is selected from the group consisting of a biologically active material, drug, pharmaceutical, pharmaceutical excipient, therapeutic agent, medicinal agent, sugar, pigment, toxin, insecticide, viral material, diagnostic aid, agricultural chemical, nutritional material, protein, alkyloid, alkaloid, peptide, animal extract, plant extract, dye, explosive, paint, cosmetic, antigen, enzyme, catalyst, nucleic acid, zeolite, polymer precursor, and combinations thereof.7. The apparatus as defined in claim 6 wherein the solute further comprises a polymer, filler, disintegrant, binder, solubilizer, stabilizer, buffer or combinations thereof.8. The apparatus as defined in claim 6 wherein the solution further comprises a surfactant or a processing aid.9. The apparatus as defined in claim 1 wherein the supercritical fluid comprises carbon dioxide, nitrous oxide, propane, or ethane.10. The apparatus as defined in claim 1 further comprising a controller communicating with the solution source, the supercritical fluid source, the mixer and the freeze-dry apparatus, the controller being operable to:control flow rates of solution and supercritical fluid from the respective solution source and supercritical fluid source to the mixer, control the mixing rate of the mixer to mix the solution and supercritical fluid to form the mixture, control the mixer to supply the mixture to the expansion assembly at a predetermined flow rate, and control the freeze-dry apparatus to sublime the solid solvent particles at a predetermined rate of solvent extraction. 11. The apparatus as defined in claim 1 wherein the mixer is further operable to mix the solution and the supercritical fluid such that the solution is saturated with the supercritical fluid or is dispersed within the supercritical fluid.12. The apparatus as defined in claim 1 wherein the frozen solvent constitutes the same phase as the solute particles.13. An apparatus for producing particles comprising:a solution source supplying a solution comprising a solvent and a solute; a fluid source supplying a compressed fluid, wherein the compressed fluid comprises a first fluid component and a second fluid component that have freezing points at different temperatures relative to each other, and the first fluid component has a higher freezing point relative to the second fluid component, and the first fluid component operates as a blowing or expanding agent and the second fluid component operates as a freezing agent; a mixer in fluid communication with the sources for mixing the solution and the compressed fluid together to form a mixture, and for maintaining the mixture at a first pressure sufficiently high so as to maintain the compressed fluid in a compressed state; an expansion assembly in fluid communication with the mixer for spraying the mixture across a pressure drop to form mixture droplets, the expansion assembly comprising a nozzle configured so that the solution and fluid are sprayed therethrough, the nozzle being further configured to have a contra-current, co-axial, single or multiple opening configuration, the mixture droplets comprising the solute and frozen solvent; and a freeze-dry apparatus that is in communication with the expansion assembly for subliming the frozen solvent, and thereby removing the frozen solvent from the solute, whereby solute particles are produced that are generally free of the solvent. 14. The apparatus as defined in claim 13 wherein the blowing or expanding agent and the freezing agent have different chemical structures from each other, and optionally have the same or a different temperature immediately subsequent to mixing with the solution.
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