Pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-10792256-B2
Application number	US-201716334144-A
Country	US
Kind code	B2
Filing date	Sep 18, 2017
Priority date	Sep 19, 2016
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable derivatives thereof; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a).

First claim

The invention claimed is:

1. A pharmaceutical composition for a metered dose inhaler comprising:
(i) a drug component consisting of at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable salts thereof either alone or together with at least one long acting muscarinic antagonist (LAMA) and/or at least one corticosteroid selected from mometasone, beclomethasone, fluticasone and the pharmaceutically acceptable salts and esters thereof; and
(ii) a propellant component comprising 1,1-difluoroethane (HFA-152a), wherein the composition contains greater than 0.5 ppm and less than 500 ppm of water based on the total weight of the pharmaceutical composition.

2. A pharmaceutical composition for a metered dose inhaler comprising:
(i) a drug component consisting of at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable salts thereof either alone or together with at least one long acting muscarinic antagonist (LAMA) and/or at least one corticosteroid selected from mometasone, beclomethasone, fluticasone and the pharmaceutically acceptable salts and esters thereof; and
(ii) a propellant component comprising 1,1-difluoroethane (HFA-152a), wherein the composition contains greater than 0.5 ppm and less than 1000 ppm of oxygen based on the total weight of the pharmaceutical composition.

3. The pharmaceutical composition of claim 1 , wherein the at least one salmeterol compound is salmeterol.

4. The pharmaceutical composition of claim 1 , wherein the drug component includes at least one long acting muscarinic antagonist (LAMA).

5. The pharmaceutical composition of claim 4 , wherein the at least one long acting muscarinic antagonist (LAMA) is a pharmaceutically acceptable salt of glycopyrrolate, or is selected from the group consisting of umeclidinium, ipratropium, tiotropium and aclidinium and the pharmaceutically acceptable salts thereof.

6. The pharmaceutical composition of claim 1 , wherein the drug component includes at least one corticosteroid selected from fluticasone and the pharmaceutically acceptable salts and esters thereof; or the drug component includes at least one corticosteroid selected from fluticasone and fluticasone propionate.

7. The pharmaceutical composition of claim 1 , wherein at least 90 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).

8. The pharmaceutical composition of claim 1 , wherein the propellant component is entirely 1,1-difluoroethane (HFA-152a).

9. The pharmaceutical composition of claim 7 , wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.

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

11. The pharmaceutical composition of claim 1 , further comprising a polar excipient.

12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is free of one or more of the following: (i) perforated microstructures; (ii) polymers having amide and/or carboxylic acid ester repeating structural units; (iii) acid stabilizers; (iv) pharmaceutically acceptable salts of both cromoglycic acid and nedocromil; (v) polar excipients; and (vi) ethanol.

13. The pharmaceutical composition of claim 1 , wherein the composition after storage in uncoated aluminum containers at 40° C. and 75% relative humidity for 6 months will produce less than 0.4% by weight of impurities from the degradation of the at least one salmeterol compound based on the total weight of the at least one salmeterol compound and the impurities.

14. The pharmaceutical composition of claim 1 , wherein at least 98.0% by weight of the at least one salmeterol compound that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminum containers at 40° C. and 75% relative humidity for 6 months.

15. The pharmaceutical composition of claim 1 , wherein the composition when delivered from a metered dose inhaler yields a fine particle fraction of the at least one salmeterol compound which is at least 40 weight % of the emitted dose of the at least one salmeterol compound.

16. The pharmaceutical composition of claim 1 , wherein the composition is in the form of a suspension.

17. The pharmaceutical composition of claim 10 , wherein the composition comprises a suspension of drug particles and wherein the surfactant component is not present as a surface coating on the suspended drug particles.

18. The pharmaceutical composition of claim 1 , wherein the composition is in the form of a solution.

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

20. The pharmaceutical composition of claim 6 which is adapted to deliver the compounds making up the drug component in approximately the same proportions that they occur in the pharmaceutical composition.

21. The pharmaceutical composition of claim 4 , wherein the at least one long acting muscarinic antagonist (LAMA) is glycopyrronium bromide.

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

23. The pharmaceutical composition of claim 10 , wherein the at least one surfactant compound is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol surfactants, oleic acid and lecithin.

24. The pharmaceutical composition of claim 11 , wherein the polar excipient is ethanol.

25. The pharmaceutical composition of claim 2 , wherein the at least one salmeterol compound is salmeterol.

26. The pharmaceutical composition of claim 2 , wherein the drug component includes at least one long acting muscarinic antagonist (LAMA).

27. The pharmaceutical composition of claim 26 , wherein the at least one long acting muscarinic antagonist (LAMA) is a pharmaceutically acceptable salt of glycopyrrolate, or is selected from the group consisting of umeclidinium, ipratropium, tiotropium and aclidinium and the pharmaceutically acceptable salts thereof.

28. The pharmaceutical composition of claim 2 , wherein the drug component includes at least one corticosteroid selected from fluticasone and the pharmaceutically acceptable salts and esters thereof; or the drug component includes at least one corticosteroid selected from fluticasone and fluticasone propionate.

29. The pharmaceutical composition of claim 2 , wherein at least 90 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).

30. The pharmaceutical composition of claim 2 , wherein the propellant component is entirely 1,1-difluoroethane (HFA-152a).

31. The pharmaceutical composition of claim 29 , wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.

32. The pharmaceutical composition of claim 2 , further comprising a surfactant component comprising at least one surfactant compound.

33. The pharmaceutical composition of claim 30 , wherein the at least one surfactant compound is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol surfactants, oleic acid and lecithin.

34. The pharmaceutical composition of claim 2

Assignees

• Mexichem Fluor Sa De Cv

Inventors

• Corr Stuart
• Noakes Timothy James

Classifications

• A61K31/56

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

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title

• A61K9/124

  characterised by the propellant · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title