Preservation of bioactive materials by freeze dried foam
This invention provides methods, systems and compositions to preserve bioactive materials in a dried foam matrix. Methods provide non-boiling foam generation and penetration of preservative agents at temperatures near the phase transition temperature of the membranes. Bioactive materials can be preserved with high initial viability in a freeze-foam process employing low temperature secondary drying.
1. A method for preparing a stable dry foam composition comprising a bioactive material, which method comprises:
preparing a formulation comprising the bioactive material, and a polyol or polymer, in a solvent;
expanding the formulation into a foam which comprises an aspect ratio of 10 or more;
freezing the foam;
primary drying the frozen foam by sublimation at a foam temperature of 0° C. or less; and,
secondary drying the foam in an environment with a temperature of 25° C. or less for a time sufficient to reduce the foam to a residual moisture of 10 percent or less.
2. The method of claim 1 , wherein the bioactive material comprises a virus or bacteria.
3. The method of claim 1 , wherein the bioactive material comprises a Listeria bacterium or Influenza strain.
4. The method of claim 2 , wherein the method further comprises holding the formulation within 2° C. of a membrane phase transition temperature of the virus or bacteria.
5. The method of claim 1 , wherein:
the foam comprises a thickness of 2 mm or less;
the foam is dried for a time sufficient to reduce the foam to a residual moisture of 5 percent or less;
a secondary drying temperature remains below the glass transition temperature of the foam; or
the primary drying or secondary drying comprise lyophilization at a pressure of 100 Torr or less.
6. The method of claim 1 , further comprising grinding the dry foam to a powder with an average particle size from about 0.1 um to about 100 um; or reconstituting the foam in liquid, or grinding the foam into a powder for.
7. A method for preparing a stable dry foam composition comprising a bioactive material, which method comprises:
preparing a formulation comprising the bioactive material, and a polyol or polymer, in a solvent;
expanding the formulation into a foam which comprises an aspect ratio of 10 or more;
freezing the foam;
primary drying the foam by sublimation at a temperature wherein the foam is frozen or remains below the glass transition temperature of the foam; and,
secondary drying the foam in an environment of 25° C. or less for a time sufficient to reduce the foam to a 10 percent residual moisture or less.
8. The method of claim 7 , wherein the bioactive material comprises a virus or bacteria.
9. The method of claim 8 , further comprising holding the formulation at a temperature within 2° C. of a membrane transition temperature of the bioactive material for 2 or more minutes before expanding the foam.
10. The method of claim 7 , wherein the bioactive material comprises a Listeria bacterium or Influenza strain.
11. The method of claim 7 , wherein the foam has a thickness of 2 mm or less.
12. The method of claim 7 , wherein the foam is dried for a time sufficient to reduce the foam to a residual moisture of 5 percent or less.
13. A system for preparing a stable dry foam composition comprising a bioactive material, which system comprises:
an environment control chamber comprising control of internal temperature and internal pressure; and,
a foam within the chamber, which foam comprises the bioactive material, and a polyol or polymer, in a solvent;
wherein, the foam has a thickness of 2 mm or less or an aspect ratio of 10 or more; and,
wherein the system is configured to dry the foam to a 10 percent residual moisture or less, at a temperature of 25° C. or less, over a time period of 2 days or less.
14. The method of claim 13 , wherein the bioactive material comprises a virus or bacteria.
15. The method of claim 13 , wherein the bioactive material comprises a Listeria bacterium or Influenza strain.
16. The method of claim 13 , wherein the foam has a thickness of 1 mm or less or an aspect ratio of 100 or more.
17. A dry foam composition comprising:
a bacteria or virus in a dry foam matrix comprising a 10 percent residual moisture or less; wherein the matrix comprises a polyol or polymer; and,
wherein the dry foam was prepared from a liquid formulation of the bacteria or virus with less than a 0.5 log 10 loss of viability.
18. The composition of claim 17 , wherein the dry foam is a freeze-dried foam.
19. The composition of claim 17 , wherein the dry foam has not been exposed to a temperature greater than 25° C.; or
wherein the foam comprises a 5 percent residual moisture or less.
20. The composition of claim 17 , wherein the bioactive material comprises a Listeria bacterium or Influenza strain.
21. The method of claim 1 , wherein said secondary drying comprises holding the environment at a temperature not greater than 25° C. until the residual moisture is 10 percent or less.
22. The method of claim 1 , further comprising raising the environment temperature from 25° C. or less to greater than 25° C. after the residual moisture is 10 percent or less.