Method of monitoring a freeze drying process

• US 20030116027A1
• Filed: 10/17/2002
• Published: 06/26/2003
• Est. Priority Date: 04/19/2000
• Status: Active Grant

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Brulls, Mikael Johan Alvin
• Granted Patent: US 6,848,196 B2
• Time in Patent Office: Days
• US Class Current: 99/279
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

A method of monitoring a freeze-drying process in an apparatus (1) holding one or more samples (9) of a material to be freeze dried, comprises the steps of directing input radiation onto the sample (9), the input radiation forming output radiation by interaction with the sample (9); collecting at least part of the output radiation and leading the thus collected radiation to a radiation analyzer (11); and analyzing the collected radiation spectroscopically in the radiation analyzer (11) to obtain a measurement value of one or more freeze-drying parameters of the sample (9), such as the temperature of the sample (9) and/or the content of a solvent in the sample (9) and/or the structure of the sample (9).

Claims

1. A method of monitoring a freeze-drying process in an apparatus (1) holding one or more samples (9) of a material to be freeze dried, characterized by the steps of directing input radiation onto the sample (9), said input radiation forming output radiation by interaction with the sample (9);

collecting at least part of said output radiation and leading the thus collected radiation to a radiation analyzer (11); and

analyzing the collected radiation spectroscopically in the radiation analyzer (11) to obtain a measurement value of one or more freeze-drying parameters of the sample (9).

2. A method according to claim 1, wherein said collected radiation comprises input radiation that has been diffusely reflected on the sample (9), and wherein said step of analyzing is at least partly based on said reflected input radiation.

3. A method according to claim 1 or 2, comprising the initial steps of arranging a radiation-transmitting means (12) in the vicinity of at least one of the samples (9), and directing said input radiation from said radiation-transmitting means (12) onto the sample (9).

4. A method according to anyone of claim 3, wherein said collected radiation is led to said radiation analyzer (11) through said radiation-transmitting means (12).

5. A method according to claim 3 or 4, wherein said radiation-transmitting means (12) includes at least one optical fiber.

6. A method according to anyone of claims 3-5, wherein the sample (9) is enclosed in a container (20), and said radiation-transmitting means (12) directs said input radiation onto the sample (9) through a wall portion of said container (20).

7. A method according to anyone of claims 3-5, wherein said radiation-transmitting means (12) is in contact with said sample.

8. A method according to anyone of the previous claims, wherein said measurement value is fed to a control unit (14), and wherein said control unit (14) controls the freeze-drying process on basis, at least partly, of said measurement value.

9. A method according to claim 8, wherein the freeze-drying process is controlled by operation of means (4, 6) effecting an adjustment of a total pressure and/or a temperature in the apparatus (1).

10. A method according to anyone of the previous claims, wherein said input radiation comprises near infrared (NIR) radiation, and said collected radiation is analyzed spectroscopically in the near infrared wavelength region.

11. A method according to anyone of the previous claims, wherein said input radiation and said collected radiation is led through several optical fibers (12) to and from the sample (9), and wherein said radiation analyzer (11) performs a separate analysis of the collected radiation led through each optical fiber (12) to obtain a respective measurement value.

12. A method according to anyone of the previous claims, wherein said one or more parameters are related to one or more physicochemical properties of the sample (9).

13. A method according to anyone of the previous claims, wherein one of said freeze-drying parameters comprises a temperature of the sample (9).

14. A method according to anyone of the previous claims, wherein one of said freeze-drying parameters comprises a content of a solvent, such as water, in the sample (9).

15. A method according to anyone of the previous claims, wherein one of said freeze-drying parameters corresponds to a structure of the sample (9), such as a macroscopic structure, a degree of crystallinity or polymorphism.

16. A method according to anyone of the previous claims, wherein the analysis in the radiation analyzer (11) is based on chemometric methods, such as multivariate statistical analysis.

17. A method according to anyone of the previous claims, wherein the step of analyzing comprises the steps of generating a sample vector of data values, and condensing said data values into said measurement value.

18. A method according to claim 17, wherein each data value corresponds to an intensity of the collected radiation at a given wavelength.

19. A method according to anyone of the previous claims, wherein the step of performing a measurement on the sample (9) is carried out on a final product in order to determine the quality of the freeze-dried material.

20. Use of a method according to anyone of claims 1-19 for monitoring a temperature of the sample (9), at least during a sublimation step of the freeze-drying process.

21. Use of a method according to anyone of claims 1-19 for determining an end point of the ice formation process in the sample (9) during an initial freezing step of the freeze-drying process.

22. Use of a method according to anyone of claims 1-19 for monitoring a structure of the sample (9) during an initial freezing step of the freeze-drying process.

23. Use of a method according to anyone of claims 1-19 for monitoring an annealing operation performed during an initial freezing step of the freeze-drying process, said annealing process being monitored via temperature and/or structure of the sample (9).

24. Use of a method according to anyone of claims 1-19 for determining an end point of a sublimation step of the freeze-drying process.

25. Use of a method according to anyone of claims 1-19 for monitoring a sublimation rate during a sublimation step of the freeze-drying process.

26. Use of a method according to anyone of claims 1-19 for determining an end point of a desorption step of the freeze-drying process.

27. Use of a method according to anyone of claims 1-19 for monitoring a drying rate during a desorption step of the freeze-drying process.

28. Use of a method according to anyone of claims 1-19 for monitoring a content of a solvent other than water in the sample (9), at least during a desorption step of the freeze-drying process.

29. A method of monitoring a freeze-drying process in an apparatus (1) holding at least one sample (9) of a material to be freeze dried, characterized in that near infrared spectroscopy (NIRS) is used to obtain a measurement value of one or more freeze-drying parameters related to one or more physicochemical properties of said at least one sample (9).