Sterilization of pharmaceuticals

• US 20030103864A1
• Filed: 09/30/2002
• Published: 06/05/2003
• Est. Priority Date: 11/24/2000
• Status: Active Grant

• Current Assignee: Allergan Pharmaceuticals International Ltd. (Abbvie Incorporated)
• Original Assignee: Breath Limited (Abbvie Incorporated)
• Inventors: McAffer, Ian G.C., Purohit, Kailash S.
• Granted Patent: US 6,863,865 B2
• Time in Patent Office: Days
• US Class Current: 422/1
• CPC Class Codes: A61L 2/0023 Heat
• CPC Class Codes: C07J 5/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond

Abstract

A method of sterilizing a pharmaceutical composition containing a suspension of a pharmaceutical comprises rapidly heating the pharmaceutical composition from ambient temperature to an elevated temperature, maintaining it at or above the elevated temperature for a period of time, and rapidly cooling the pharmaceutical composition to ambient temperature.

Claims

1. A method of sterilizing a pharmaceutical composition, comprising rapidly heating the pharmaceutical composition from ambient temperature to an elevated temperature, maintaining it at or above the elevated temperature for a period of time, and rapidly cooling the pharmaceutical composition to ambient temperature, wherein the pharmaceutical composition is or contains a suspension of a pharmaceutically active agent.

2. The method of claim 1, comprising increasing the temperature of the composition from the ambient temperature to the elevated temperature in less than 5 seconds.

3. The method of claim 1, comprising decreasing the temperature of the composition from the elevated temperature to ambient temperature in less than 5 seconds.

4. The method of claim 1, comprising heating the composition to an elevated temperature exceeding 130°

C.

5. The method of claim 1, wherein the period of time is less than 20 seconds and greater than 2 seconds.

6. The method of claim 1, wherein the pharmaceutical composition comprises a drug in suspension, water or another solvent and, optionally, surfactants and/or preservatives.

7. The method of claim 6 wherein the composition is a glucocorticosteroid composition, such as a budesonide suspension.

22. A pharmaceutical suspension obtained by the method of claim 1.

23. A suspension of budesonide obtained by the method of claim 1.

8. A method of treating a pharmaceutical composition to reduce its microbial load, comprising rapidly heating the pharmaceutical composition from ambient temperature to an elevated temperature, maintaining it at or above the elevated temperature for a period of time, and rapidly cooling the pharmaceutical composition to ambient temperature, wherein the pharmaceutical composition comprises a drug in suspension.

9. The method of claim 8, comprising maintaining the composition at or above the elevated temperature for a time necessary for sterilization to be achieved.

24. A pharmaceutical suspension obtained by the method of claim 8.

25. A suspension of budesonide obtained by the method of claim 8.

10. A method of sterilizing a concentrated formulation for use in a pharmaceutical composition, comprising rapidly heating the concentrated formulation from ambient temperature to an elevated temperature, maintaining it at or above the elevated temperature for a period of time, and rapidly cooling the concentrated formulation to ambient temperature, wherein the concentrated formulation is or contains a suspension of a pharmaceutically active agent.

11. The method of claim 10, comprising increasing the temperature of the composition from the ambient temperature to the elevated temperature in less than 5 seconds.

12. The method of claim 10, comprising decreasing the temperature of the composition from the elevated temperature to ambient temperature in less than 5 seconds.

13. The method of claim 10, comprising heating the composition to an elevated temperature exceeding 130°

C.

14. The method of claim 10, wherein the period of time is less than 20 seconds and greater than 2 seconds.

15. The method of claim 10, wherein the concentrated formulation is selected from

a pharmaceutical agent and a surfactant;

a suspension of a drug in a surfactant solution; and

a suspension of a drug in water or another solvent.

16. A method of sterilizing a pharmaceutical composition, characterized in that:

the sterilization is carried out by “

square wave heating”

; and

the sterilization is carried out continuously,

wherein the composition comprises a drug in suspension.

17. The method of claim 16, wherein square wave heating comprises rapidly heating the pharmaceutical composition from ambient temperature to an elevated temperature, maintaining it at or above the elevated temperature for a period of time, and rapidly cooling the pharmaceutical composition to ambient temperature.

18. The method of claim 16, further comprising dispensing sterilized pharmaceutical composition into storage vessels and sealing the storage vessels in a continuous process.

19. The method of claim 18 wherein dispensing is by the “

blow-fill-seal”

method.

20. The method of claim 18, wherein the storage vessels are selected from pre-sterilized ampoules, typically of polymeric material, metal or glass.

21. The method of claim 18, optionally comprising diluting a sterile concentrate by a bulk composition under sterile conditions prior to dispensing into storage vessels.