Lyophilization system and method

Abstract

System and method for lyophilization or freeze-drying is provided. During the freezing step, the material or solution to be frozen is initially brought to a temperature near or below its freezing temperature after which the pressure in the freeze-dryer chamber is reduced to induce nucleation of the material.

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 freezing 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 freezing process with depressurized nucleation in accordance with the present methods;

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

FIG. 4 is a schematic representation of a lyophilization system in accordance with the present invention.

Claims

1. A method of lyophilizing a material comprising the steps of: cooling the material in a chamber at a prescribed cooling rate;decreasing the pressure in the chamber to induce nucleation of freezing in the material;further cooling the nucleated material to or below a final temperature to freeze the material;drying the frozen material to produce a dried product having reduced moisture or solvent.

2. The method of lyophilizing as set forth in claim 1 wherein the step of cooling the material further comprises cooling the material to a temperature near or below a phase transition temperature.

3. The method of lyophilizing as set forth in claim 1 wherein the step of cooling the material further comprises cooling the material to a metastable state.

4. The method of lyophilizing as set forth in claim 1 wherein the step of further cooling the nucleated material further comprises cooling the nucleated material to or below a final temperature completing freezing of the material.

5. The method of lyophilizing as set forth in claim 1 wherein the step of decreasing the pressure is initiated when the material attains a desired nucleation temperature.

6. The method of lyophilizing as set forth in claim 1 wherein the step of decreasing the pressure is initiated at a desired time after initiation of the cooling step wherein the material reaches a phase transition temperature or below.

7. The method of lyophilizing as set forth in claim 1 wherein the material further comprises a biopharmaceutical material, a pharmaceutical material, a chemical material, a biological material, a foodstuff or combinations thereof.

8. The method of lyophilizing as set forth in claim 1 wherein the step of decreasing the pressure occurs in a gas atmosphere within the chamber.

9. The method of lyophilizing as set forth in claim 8 wherein the gas atmosphere within the chamber comprises argon, nitrogen, helium, air, water vapor, oxygen, carbon dioxide, neon, xenon, krypton, hydrogen, or mixtures thereof.

10. The method of lyophilizing as set forth in claim 8 wherein the gas atmosphere is pressurized above ambient pressure.

11. The method of lyophilizing as set forth in claim 10 wherein the gas atmosphere is pressurized between ambient pressure and 25 psi above ambient pressure.

12. The method of lyophilizing as set forth in claim 1 wherein the material is cooled to a temperature ranging from the phase transition temperature to about 20° C. below the phase transition temperature prior to depressurization.

13. The method of lyophilizing as set forth in claim 1 wherein the material is cooled to a temperature ranging from the phase transition temperature to about 5° C. below the phase transition temperature prior to depressurization.

14. The method of lyophilizing as set forth in claim 1 wherein the pressure is decreased by about 14 psi or more.

15. The method of lyophilizing as set forth in claim 1 wherein the pressure is decreased by about 7 psi or more.

16. The method of lyophilizing as set forth in claim 1 wherein the pressure is decreased such that an absolute pressure ratio, Pi/Pf, is about 1.2 or greater.

17. The method of lyophilizing as set forth in claim 1 wherein the pressure is decreased at a pressure rate drop, ΔP/Δt, greater than about 0.2 psi per second.

18. The method of lyophilizing as set forth in claim 1 wherein the pressure is decreased in 40 seconds or less.

19. The method of claim 7 wherein the material, including starting material and reconstituted material, further comprises one or more components selected from the group consisting of: live virus; attenuated virus; nucleic acids; monoclonal antibodies; polyclonal antibodies; proteins; peptides; or polypeptides.

20. The method of lyophilizing as set forth in claim 19 wherein components of reconstituted material exhibit a function or activity similar to the function or activity associated with components of a starting material.

21. The method of claim 19 wherein components of reconstituted material exhibit a function or activity improved over the function or activity associated with components of reconstituted material from a stochastically nucleated material.

22. The method of claim 1 wherein components of reconstituted material exhibit a desired function or activity and the material to be lyophilized requires less mitigating constituents to achieve the desired function or activity than components from material that is stochastically nucleated.

23. The method of lyophilizing as set forth in claim 1 wherein a material reconstituted from the dried product exhibits a structure similar to the structure associated with a starting material.

24. The method of lyophilizing as set forth in claim 1 wherein the material is held in a plurality of containers or vials and the dried product obtained from the plurality of containers or vials exhibit relatively uniform reconstitution time.

25. The method of lyophilizing as set forth in claim 1 wherein the material is held in a plurality of containers or vials and the dried product obtained from the plurality of containers or vials exhibit relatively uniform residual moisture or solvent levels.

26. The method of lyophilizing as set forth in claim 1 wherein the step of drying the frozen material is performed in less than 96 hours.

27. The method of claim 1 wherein time required for drying the frozen material is less than the time required for drying the frozen material that is stochastically nucleated.

28. A freeze-dryer system comprising: a chamber having a controlled gas atmosphere and one or more shelves adapted to hold one or more containers or vials of a material;a means to control the temperature of the shelves within the chamber so as to control the temperature of the material;a condenser coupled to the chamber and adapted to remove any solvent or moisture from the chamber; anda means to control the pressure of the chamber to rapidly depressurize the chamber to nucleate a phase transition in the material during freezing and to maintain a low pressure during drying.

29. A method of lyophilizing a material comprising the steps of: bringing the material to a temperature near or below a phase transition temperature in a pressurized gas atmosphere;decreasing the pressure to nucleate freezing in the material; anddrying the material to produce a dried product having reduced moisture or solvent.