Aerosol formulation for COPD

Patent metadata

Field	Value
Publication number	US-12357568-B2
Application number	US-202318153096-A
Country	US
Kind code	B2
Filing date	Jan 11, 2023
Priority date	Dec 23, 2009
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

Stable aerosol solution formulations comprising glycopyrronium bromide are useful for administration to patients with COPD and other respiratory conditions.

First claim

The invention claimed is:

1. A pharmaceutical composition for use with a pressurized metered dose inhaler, comprising glycopyrronium bromide dissolved in HFA-134a and ethanol, wherein:
the composition comprises an amount of hydrochloric acid equivalent to 0.005 to 1.0 μg/μl of 1M hydrochloric acid;
the composition comprises glycopyrronium bromide in an amount of 0.015 to 0.04% w/w of the composition;
the composition comprises ethanol in an amount of 10 to 15% w/w of the composition;
the composition comprises HFA-134a in an amount of 85 to 90% w/w of the composition;
the composition comprises formoterol fumarate; and
the composition comprises beclometasone dipropionate.

2. A composition according to claim 1 , wherein said composition comprises an amount of hydrochloric acid equivalent to 0.099 to 0.74 μg/μl of 1M hydrochloric acid.

3. A composition according to claim 1 , wherein said composition comprises an amount of hydrochloric acid equivalent to 0.18 to 0.32 μg/μl of 1M hydrochloric acid.

4. A composition according to claim 1 , wherein the glycopyrronium bromide is the racemic mixture (3S,2′R), (3R,2'S)-3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.

5. A composition according to claim 1 , comprising water in an amount less than 0.5% w/w of the composition.

6. A composition according to claim 1 , comprising water in an amount 0.005 to 0.5% w/w of the composition.

7. A composition according to claim 1 , wherein the composition is free of excipients other than the ethanol, the HFA-134a, and the hydrochloric acid.

8. A composition according to claim 1 , wherein the concentration of ethanol in the pharmaceutical composition is 12% w/w.

9. A composition according to claim 3 , wherein the concentration of ethanol in the pharmaceutical composition is 12% w/w.

10. A composition according to claim 3 , comprising water in an amount 0.005 to 0.5% w/w of the pharmaceutical composition.

11. A composition according to claim 8 , comprising water in an amount 0.005 to 0.5% w/w of the pharmaceutical composition.

12. A composition according to claim 9 , comprising water in an amount 0.005 to 0.5% w/w of the pharmaceutical composition.

13. A method of filling an aerosol canister with a pharmaceutical composition according to claim 1 , comprising:
a) preparing a solution comprising glycopyrronium bromide, formoterol fumarate, beclometasone dipropionate, ethanol, hydrochloric acid, and optionally a low volatility component;
b) filling an open canister with the solution;
c) placing a valve onto the canister and crimping; and
d) pressure-filling the canister with HFA-134a propellant through the valve.

14. A metered dose inhaler, comprising a pharmaceutical composition according to claim 1 .

15. A metered dose inhaler according to claim 14 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

16. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 3 .

17. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 8 .

18. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 9 .

19. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 10 .

20. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 11 .

21. A pressurized metered dose inhaler, comprising a pharmaceutical composition according to claim 12 .

22. A pressurized metered dose inhaler according to claim 16 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

23. A pressurized metered dose inhaler according to claim 17 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

24. A pressurized metered dose inhaler according to claim 18 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

25. A pressurized metered dose inhaler according to claim 19 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

26. A pressurized metered dose inhaler according to claim 20 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

27. A pressurized metered dose inhaler according to claim 21 , comprising a metering valve capable of delivering a volume of about 63 μl of pharmaceutical composition per actuation.

28. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 1 to a subject in need thereof.

29. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 3 to a subject in need thereof.

30. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 2 to a subject in need thereof.

31. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 4 to a subject in need thereof.

32. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 5 to a subject in need thereof.

33. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 5 to a subject in need thereof.

34. A method for the treatment of a respiratory disorder selected from the group consisting of asthma and chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 7 to a subject in need thereof.

35. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 1 to a subject in need thereof.

36. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 3 to a subject in need thereof.

37. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 8 to a subject in need thereof.

38. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 9 to a subject in need thereof.

39. A method for treatment of asthma, comprising administering an effective amount of a composition according to cl

Assignees

• Chiesi Farm Spa

Inventors

• Bonelli Sauro
• Usberti Francesca
• Zambelli Enrico

Classifications

• B65B31/10

  Adding propellants in solid form to aerosol containers · CPC title

• B65B31/06

  the nozzle being arranged for insertion into, and withdrawal from, the mouth of a filled container and operating in conjunction with means for sealing the container mouth · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K47/06

  Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title