Method of inducing nucleation of a material

Abstract

Methods of inducing nucleation of a material is provided. The disclosed methods comprise the steps of bringing the material to a temperature near or below a phase transition temperature and altering the pressure to induce nucleation of the material. The disclosed methods are useful in freeze-drying processes, particularly pharmaceutical freeze-drying processes.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other aspects, features, and advantages of the present invention will be more apparent from the following, more detailed description thereof, presented in conjunction with the following drawings, wherein:

FIG. 1 is a graph depicting the temperature versus time plot of a solution undergoing a stochastic nucleation process and further showing the range of nucleation temperatures of the solution;

FIG. 2 is a graph depicting the temperature versus time plot of a solution undergoing an equilibrated cooling process with depressurized nucleation in accordance with the present methods; and

FIG. 3 is a graph depicting the temperature versus time plot of a solution undergoing a dynamic cooling process with depressurized nucleation in accordance with the present methods.

Claims

1. A method of inducing nucleation of a phase transition in a material comprising the steps of: bringing the material to a temperature near or below a phase transition temperature; anddecreasing the pressure proximate the material to induce nucleation of the phase transition in the material.

2. The method of claim 1 wherein the material is cooled to a metastable state.

3. The method of claim 1 further comprising the step of cooling of the nucleated material after depressurization to or below a final temperature to further the phase transition of the material.

4. The method of claim 1 wherein depressurization is initiated when the material attains a desired nucleation temperature.

5. The method of claim 1 wherein depressurization is initiated at a desired time after initiation of the method and when the temperature of the material reaches the phase transition temperature or below.

6. The method of claim 1 further comprising the step of reconstituting the material.

7. The method of claim 1 wherein the material is selected from the group consisting of gases, liquids, solutions, suspensions, gels, mixtures, or components within a suspension, solution or mixture.

8. The method of claim 1 wherein the material is a solution and the phase transition temperature is the thermodynamic freezing point of the solution.

9. The method of claim 1 wherein the material is a solution with one or more dissolved substances and the phase transition temperature is a saturation temperature at which a dissolved substance will precipitate or crystallize out of the solution.

10. The method of claim 7 wherein the material further comprises a biopharmaceutical material, a pharmaceutical material, a chemical material, a biological material, a foodstuff or combinations thereof.

11. The method of claim 1 wherein the material is confined in the presence of a gas atmosphere.

12. The method of claim 11 wherein the gas atmosphere comprises argon, nitrogen, helium, air, water vapor, oxygen, carbon dioxide, neon, xenon, krypton, hydrogen, or mixtures thereof.

13. The method of claim 11 further comprising the step of pressurizing the atmosphere surrounding the material.

14. The method of claim 1 wherein the material is brought to a temperature ranging from the phase transition temperature to about 20° C. below the phase transition temperature prior to depressurization.

15. The method of claim 1 wherein the material is brought to a temperature ranging from the phase transition temperature to about 5° C. below the phase transition temperature prior to depressurization.

16. The method of claim 1 wherein the pressure is decreased by an amount equal to or greater than about 14 psi.

17. The method of claim 1 wherein the pressure is decreased by an amount greater than about 7 psi.

18. The method of claim 1 wherein the pressure is decreased such that an absolute pressure ratio, Pi/Pf, is about 1.2 or greater.

19. The method of claim 1 wherein the pressure is decreased at a pressure rate drop, ΔP/Δt, greater than about 0.2 psi per second.

20. The method of claim 1 wherein the pressure is decreased in 40 seconds or less.

21. The method of claim 6 wherein the material, including starting material and reconstituted material contains a component comprising: live viruses; attenuated viruses; nucleic acids; monoclonal antibodies; polyclonal antibodies; biomolecules; nonpeptide analogues; peptides; or proteins.

22. The method of claim 21 wherein the component of the reconstituted material exhibits a function or activity similar to the function or activity associated with the component of the starting material.

23. The method of claim 21 wherein the component of the reconstituted material exhibits a function or activity improved over the function or activity associated with the component of the material nucleated stochastically.

24. The method of claim 21 wherein the component of the reconstituted material exhibits a structure similar to the structure associated with the component of the starting material.

25. The method of claim 21 wherein the material is held in a plurality of containers and the reconstituted material from all containers exhibits uniform properties.

26. A method of controlling the freezing process of a material comprising the steps of: cooling the material at a prescribed cooling rate;rapidly decreasing the pressure to nucleate freezing within the material; andcontinuing cooling of the nucleated material to a prescribed final temperature to further freeze the material.

27. The method of claim 26 wherein depressurization is initiated when the material attains a desired nucleation temperature.

28. The method of claim 26 wherein depressurization is initiated a desired time after initiation of the initial cooling step and when the temperature of the material reaches the phase transition temperature or below.

29. A solidification process comprising the steps of: bringing a material to a temperature near or below a phase transition temperature;decreasing the pressure proximate the material to induce nucleation of solidification within the material; andcooling of the nucleated material to a prescribed final temperature to further solidification.

30. The solidification process of claim 29 wherein the material is a solution having one or more dissolved substances and wherein the step of decreasing the pressure proximate the material further comprises decreasing the pressure proximate the solution to induce nucleation of solidification of one or more of the substances in the solution.

31. A method of controlling the condensation process of a gas comprising the steps of: cooling the gas to a temperature near or below a phase transition temperature;decreasing the pressure to induce nucleation of condensation within the gas; andcontinuing cooling of the nucleated gas to a prescribed final temperature to further condensation.

32. A method of inducing a phase transition of a material comprising the steps of: warming the material to a temperature near or above a phase transition temperature; anddecreasing the pressure proximate the material to induce the phase transition of the material.

33. A method of phase transitioning a material comprising the steps of: bringing the material to a temperature near a phase transition temperature in a pressurized gas atmosphere; anddecreasing the pressure to induce the phase transition of the material.