Claims for Patent: 12,357,568

Summary for Patent: 12,357,568

Title:	Aerosol formulation for COPD
Abstract:	Stable aerosol solution formulations comprising glycopyrronium bromide are useful for administration to patients with COPD and other respiratory conditions.
Inventor(s):	Sauro BONELLI, Francesca Usberti, Enrico Zambelli
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US18/153,096
Patent Claims:	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 claim 10 to a subject in need thereof. 40. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 11 to a subject in need thereof. 41. A method for treatment of asthma, comprising administering an effective amount of a composition according to claim 12 to a subject in need thereof. 42. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 1 to a subject in need thereof. 43. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 3 to a subject in need thereof. 44. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 8 to a subject in need thereof. 45. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 9 to a subject in need thereof. 46. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 10 to a subject in need thereof. 47. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 11 to a subject in need thereof. 48. A method for treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a composition according to claim 12 to a subject in need thereof. 49. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 1 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 50. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 3 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 51. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 8 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 52. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 9 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 53. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 10 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 54. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 11 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 55. A method for treatment of chronic obstructive pulmonary disease, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 12 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 56. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 1 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 57. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 3 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 58. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 8 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 59. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 9 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 60. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 10 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 61. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 11 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation. 62. A method for treatment of asthma, comprising inhalation administration of an effective amount of a pharmaceutical composition according to claim 12 to a subject in need thereof via two actuations of a pressurized metered dose inhaler containing said pharmaceutical composition, wherein the pressurized metered dose inhaler has a metering valve that delivers a volume of about 63 μl of pharmaceutical composition per actuation.