Dry heat sterilization of a glucocorticosteroid

• US 6,392,036 B1
• Filed: 01/29/1999
• Issued: 05/21/2002
• Est. Priority Date: 11/14/1997
• Status: Expired due to Term

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Larrivee-Elkins, Cheryl, Karlsson, Ann-Kristin, Molin, Ove
• Primary Examiner(s): Fonda, Kathleen Kahler
• Assistant Examiner(s): Maier, Leigh C.
• Application Number:
  US09/230,781
• Time in Patent Office: 1,208 Days
• Field of Search: 540/63, 540/84, 540/85, 552/581, 552/588, 552/590, 552/598, 514/174, 514/176, 514/177, 514/178
• US Class Current: 540/63
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61L 2/0023 Heat
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids

Abstract

The invention provides a process for the sterilization of a powdered form of a glucocorticosteroid, sterile glucocorticosteroids, sterile formulations containing glucocorticosteroids and use thereof in the treatment of an allergic and/or inflammatory condition of the nose or lungs.

Claims

1. A process for the sterilization of a powder comprising a glucocorticosteroid or ester, acetal, or salt thereof, said process comprising heat treating the powder at a temperature of from 100°

C. to 130°

C., wherein the glucocorticosteroid or ester, acetal, or salt thereof contains an asymmetric acetal structure comprising 16α

,17α

-butylidenedioxy.

2. The process according to claim 1, wherein the glucocorticosteroid is an anti-inflammatory glucocorticosteroid.

3. The process according to claim 1, wherein the glucocorticosteroid or ester, acetal, or salt thereof is selected from the group consisting of budesonide, rofleponide and rofleponide palmitate.

4. The process according to claim 1, wherein the glucocorticosteroid is heat treated at a temperature of from 110 to 120°

C.

5. The process according to claim 1, wherein the glucocorticosteroid is heat treated for no more than 10 hours.

6. The process according to claim 1, wherein the glucocorticosteroid is heat treated at a temperature of from about 110°

C. to 130°

C. for no more than 8 hours.

7. The process according to claim 6, wherein the glucocorticosteroid is heat treated at a temperature of about 120°

C. for no more than 4 hours.

8. The process according to claim 6, wherein the glucocorticosteroid is heat treated at a temperature of about 120°

C. for no more than 2 hours.

9. The process according to claim 1, wherein the glucocorticosteroid contains less than about 1% (w/w) of water before the heat treatment.

10. The process according to claim 1, wherein the glucocorticosteroid powder has a mass median diameter (MMD) of less than 10 μ

m.

11. The process according to claim 1, said process being carried out under an inert gas atmosphere.

12. The process according to claim 1, wherein the amount of heat resistant spores in the powder is reduced by more than log 6 by the heat treatment.

13. The process according to claim 1, wherein the time required to reduce by 90% a population of spores in the powder is less than about 240 minutes at a temperature of from 100°

C. to 130°

C.

14. The process according to claim 1, wherein the glucocorticosteroid is heat treated at a temperature of from about 110°

C. to about 130°

C. for no more than 4 hours.

15. The process according to claim 1, wherein the glucocorticosteroid contains less than about 0.5% (w/w) of water before the heat treatment.

16. The process according to claim 1, wherein the glucocorticosteroid powder has a mass median diameter (MMD) of less than 5 μ

m.

17. The process according to claim 1, wherein the amount of heat resistant spores in the powder is reduced by more than log 7 by the heat treatment.

18. The process according to claim 1, wherein the time required to reduce by 90% a population of spores in the powder is less than 90 minutes at a temperature of from 100°

C. to 130°

C.