Claims
- 1. A method for preparing dispersible dry powders of biological macromolecules, said method comprising:
- providing an evaporable liquid medium containing a predetermined concentration of the macromolecule and excipients, wherein the macromolecule is a protein having a molecular weight above 2 kD and is present at a concentration below 10% by weight and wherein the liquid medium is an aqueous medium consisting essentially of water, the macromolecule, and the excipients;
- flowing the liquid medium and an atomization gas stream at a gas:liquid mass flow ratio above 5 under conditions selected to form droplets having an average size below 11 .mu.m;
- flowing the droplets in a heated gas stream under conditions selected to form dispersible particles of the composite material containing the biological macromolecules, said particles having a moisture content below 10% by weight and a rugosity measured by air permeametry above 2, and collecting the particles.
- 2. A method as in claim 1, wherein the total solids content in the liquid medium is in the range from 0.5% to 10% by weight.
- 3. A method as in claim 2, wherein the concentration of macromolecule is in the range from 1% to 5% by weight.
- 4. A method as in claim 1, wherein the aqueous medium consists essentially of the macromolecule and the excipients.
- 5. A method as in claim 1, wherein the average droplet size is in the range from 5 .mu.m to 11 .mu.m.
- 6. A method as in claim 1, wherein the flowing step comprises flowing the liquid medium and an atomization gas stream through a two fluid nozzle.
- 7. A method as in claim 6, wherein the gas:liquid mass flow ratio is in the range from 8 to 10.
- 8. A method as in claim 6, wherein the fluid nozzle has a liquid orifice diameter in the range from 0.015 in. to 0.075 in. and wherein the air pressure upstream of the orifice is maintained above 25 psi.
- 9. A method as in claim 1, wherein the droplets are flowed concurrently with the gas stream and wherein the gas stream has an temperature above 90.degree. C.
- 10. A method as in claim 9, wherein the gas stream has an inlet temperature above 90.degree. C. and an outlet temperature above 50.degree. C.
- 11. A method as in claim 1, wherein the droplets are dried under conditions selected to provide particles having a rugosity measured by air permeability in the range from 3 to 6.
- 12. A method as in claim 1, wherein the drying step produces a powder having at least 90% of the mass of particles in the size range from 0.4 .mu.m to 5 .mu.m and the particle collecting step comprises separating substantially the entire particle output of the drying step from the gas stream.
- 13. A method as in claim 1, further comprising packaging at least some of particles in a container after the separating step, wherein the particles have not been size classified prior to packaging.
- 14. A method as in claim 13, wherein the portion is packaged in a unit dosage container.
- 15. A method as in claim 1, wherein the particle separating step comprises passing substantially the entire gas stream through a separator which removes at least about 90% by weight of all particles having a size above 1 .mu.m from said gas stream.
- 16. A method as in claim 15, wherein the separator is a sintered metal fiber filter.
- 17. A method as in claim 15, wherein the separator is a bag filter, cartridge filter, or cloth filter.
- 18. A method as in claim 15, wherein the separator is a high efficiency cyclone.
- 19. A method as in claim 1, wherein the macromolecule is a protein selected from the group consisting of calcitonin; erythropoietin (EPO); factor IX; granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF); growth hormone; insulin; interferon alpha, interferon beta; interferon gamma; interleukin-2; luteinizing hormone releasing hormone (LHRH); somatostatin analog; vasopressin analog; follicle stimulating hormone (FSH); amylin; ciliary neurotrophic factor;, growth hormone releasing factor (GRF); insulin-like growth factor; insulinotropin; interleukin-1 receptor antagonist; interleukin-3, interleukin-4; interleukin-6; macrophage colony stimulating factor (M-CSF); nerve growth factor; parathyroid hormone; thymosin alpha 1; factor IIb/IIIa inhibitor; alpha-1 antitrypsin; anti-RSV antibody; deoxyribonuclease (DNase); bactericidal/permeability increasing protein (BPI); anti-CMV antibody; interleukin-1 receptor; and interleukin-1 receptor antagonist.
- 20. A macromolecule composition prepared by the method of any of claims 1-8 or 11-19.
BACKGROUND OF THE INVENTION
The present application is a continuation-in-part of application Ser. No. 08/423,515, filed on Apr. 14, 1995, and is also a continuation-in-part of application Ser. No. 08/383,475, filed on Feb. 1, 1995, now abn., which was a continuation-in-part of application Ser. No. 08/207,472, filed on Mar. 7, 1994, now abandoned. The full disclosures of each of these applications are incorporated herein by reference.
US Referenced Citations (89)
Foreign Referenced Citations (2)
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0 122 036 |
Oct 1984 |
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0 072 046 |
Jan 1986 |
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Continuation in Parts (3)
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207472 |
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