Pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-11826348-B2
Application number	US-202117361819-A
Country	US
Kind code	B2
Filing date	Jun 29, 2021
Priority date	Sep 19, 2016
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

A pharmaceutical composition is described. The composition may include a drug component and a propellant component. The drug component comprises at least one pharmaceutically acceptable salt of glycopyrrolate, beclomethasone diproprionate, and at least one long acting beta-2-agonist (LABA) selected from formoterol and the pharmaceutically acceptable salts thereof. The propellant component comprises 1,1-difluoroethane (HFA-152a).

First claim

The invention claimed is:

1. A pharmaceutical composition comprising:
(i) a drug component comprising at least one pharmaceutically acceptable salt of glycopyrrolate, beclomethasone diproprionate, and at least one long acting beta-2-agonist (LABA) selected from formoterol and the pharmaceutically acceptable salts thereof; and
(ii) a propellant component consisting of one or more hydrofluorocarbon and hydrocarbon propellant compounds, at least 90 weight % of which is 1,1-difluoroethane (HFA-152a),
wherein the drug component is the sole drug component in the pharmaceutical composition, and
wherein the pharmaceutical composition is in the form of a solution and optionally comprises ethanol, but is free of additional polar excipients.

2. A pharmaceutical composition comprising:
(i) a drug component comprising at least one pharmaceutically acceptable salt of glycopyrrolate, beclomethasone diproprionate, and at least one long acting beta-2-agonist (LABA) selected from formoterol and the pharmaceutically acceptable salts thereof; and
(ii) a propellant component comprising 1,1-difluoroethane (HFA-152a),
wherein the composition contains less than 500 ppm of water and less than 1000 ppm of oxygen based on the total weight of the pharmaceutical composition, and
wherein the pharmaceutical composition is in the form of a solution and optionally comprises ethanol, but is free of additional polar excipients.

3. The pharmaceutical composition of claim 1 , wherein the at least one pharmaceutically acceptable salt of glycopyrrolate is glycopyrronium bromide.

4. The pharmaceutical composition of claim 1 , wherein the at least one long acting beta-2-agonist (LABA) is formoterol fumarate dihydrate.

5. The pharmaceutical composition of claim 1 , wherein the at least one pharmaceutically acceptable salt of glycopyrrolate, beclomethasone diproprionate, and the at least one long acting beta-2-agonist (LABA) are in a micronized form.

6. The pharmaceutical composition of claim 1 , wherein at least 95 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).

7. The pharmaceutical composition of claim 1 , wherein at least 99 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).

8. A pharmaceutical composition comprising:
(i) a drug component comprising at least one pharmaceutically acceptable salt of glycopyrrolate, beclomethasone diproprionate, and at least one long acting beta-2-agonist (LABA) selected from formoterol and the pharmaceutically acceptable salts thereof; and
(ii) a propellant component comprising 1,1-difluoroethane (HFA-152a),
wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities, and
wherein the pharmaceutical composition is in the form of a solution and optionally comprises ethanol, but is free of additional polar excipients.

9. The pharmaceutical composition of claim 1 further comprising a surfactant component comprising at least one surfactant compound.

10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises ethanol.

11. The pharmaceutical composition of claim 1 which is free of one or more of (i) acid stabilizers and (ii) perforated microstructures.

12. The pharmaceutical composition of claim 1 which after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

13. The pharmaceutical composition of claim 1 which after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

14. The pharmaceutical composition of claim 1 , wherein at least 96.0% by weight of the at least one pharmaceutically acceptable salt of glycopyrrolate that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months and after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months.

15. The pharmaceutical composition of claim 1 which when delivered from a metered dose inhaler yields a fine particle fraction of the at least one pharmaceutically acceptable salt of glycopyrrolate which is at least 40 weight % of the emitted dose of the at least one pharmaceutically acceptable salt of glycopyrrolate.

16. A metered dose inhaler (MDI) fitted with a sealed and pressurized aerosol container that contains a pharmaceutical composition as claimed in claim 1 .

17. A method for treating a patient suffering or likely to suffer from a respiratory disorder, comprising:
Administering a pharmaceutically effective amount of the pharmaceutical composition of claim 1 to the patient.

Assignees

• Mexichem Fluor Sa De Cv

Inventors

• Corr Stuart
• Noakes Timothy James

Classifications

• A61K31/40 Primary

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K9/008

  comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI] · CPC title

• A61K31/4704

  2-Quinolinones, e.g. carbostyril · CPC title

• A61K31/56

  Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids · CPC title

• A61K31/573

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