Optimization of nucleation and crystallization for lyophilization using gap freezing

• US 9,279,615 B2
• Filed: 01/17/2014
• Issued: 03/08/2016
• Est. Priority Date: 09/28/2010
• Status: Expired due to Fees

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Inventors: Kuu, Wei Y.
• Primary Examiner(s): Gravini, Stephen M
• Application Number:
  US14/158,083
• Publication Number:
  US 20140190035A1
• Time in Patent Office: 781 Days
• Field of Search: 342/84, 342/87, 34/92, 62/66, 165/185, 206/438
• US Class Current: 1/1
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

This application discloses devices, articles, and methods useful for producing lyophilized cakes of solutes. The devices and articles provide for a method of freezing liquid solutions of the solute by the top and the bottom of the solution simultaneously. The as frozen solution then provides a lyophilized cake of the solutes with large and uniform pores.

Claims

1. A lyophilization device comprising:

a plurality of heat sinks that individually have a heat sink surface in thermal communication with a refrigerant, at least one of said heat sinks being disposed above another to thereby form upper and lower heat sinks;

wherein the lower heat sink surface is disposed between the upper and lower heat sinks;

a tray carrying a tray surface disposed between the upper heat sink and a lower heat sink surface; and

a thermal insulator formed extending between the container on the tray and the lower heat sink, wherein the thermal insulator is a gas having a thermal conductivity of less than about 0.2 W/mK at 25°

C.

2. The article of claim 1, wherein the heat sink comprises a refrigerant conduit in thermal communication with the heat sink surface.

3. The article of claim 2, wherein the heat sink further comprises a heat sink medium disposed between the refrigerant conduit and the heat sink surface.

4. The article of claim 1, wherein the heat sink surface and tray surface—

are separated by a fixed distance of greater than about 0.5 mm.

5. The article of claim 1 further comprising a spacer disposed between the heat sink surface and the tray surface.

6. The article of claim 5, wherein the spacer has a thickness of greater than about 0.5 mm.

7. The article of claim 1, wherein the tray carrying the tray surface is supported by a brace affixed to an internal wall of the lyophilization device.

8. The article of claim 1, wherein the thermal insulator is air having a pressure below atmospheric pressure.

9. The article of claim 1, comprising a plurality of said upper and lower heat sink pairs with interdisposed trays.

10. The article of claim 1, further comprising a container disposed on the tray.

11. The article of claim 10, wherein the container comprises a vial.

12. The article of claim 10, wherein the container holds a liquid solution.

13. The article of claim 12, wherein the liquid solution comprises a sugar.

14. The article of claim 1, wherein the thermal insulator has a thermal conductivity of less than about 0.1 W/mK at 25°

C.

15. The article of claim 14, wherein the thermal insulator has a thermal conductivity of less than about 0.05 W/mK at 25°

C.

16. The article of claim 1, wherein the heat sink surface and tray surface are separated by a fixed distance in a range of about 0.5 mm to about 50 mm.

17. The article of claim 1, wherein the heat sink surface and tray surface are separated by a fixed distance in a range of about 0.5 mm to about 10 mm.