Pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-11311502-B2
Application number	US-202016882979-A
Country	US
Kind code	B2
Filing date	May 26, 2020
Priority date	Sep 19, 2016
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

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 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 corticosteroid selected from mometasone, beclomethasone, fluticasone and the pharmaceutically acceptable salts and esters thereof; and
(ii) a propellant component consisting of one or more hydrofluorocarbon and hydrocarbon propellant compounds, where at least 90 wt % of the propellant component is 1,1-difluoroethane (HFA-152a), wherein the drug component is the sole drug component in the pharmaceutical composition wherein the composition is free of surfactants.

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

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

4. A pharmaceutical composition comprising:
(i) a drug component consisting of at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable salts thereof 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 consisting of one or more hydrofluorocarbon and hydrocarbon propellant compounds, where at least 90 wt % of the propellant component is 1,1-difluoroethane (HFA-152a),
wherein the drug component includes at least one long acting muscarinic antagonist (LAMA),
wherein the drug component is the sole drug component in the pharmaceutical composition wherein the composition is free of surfactants.

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 4 , wherein the at least one long acting muscarinic antagonist (LAMA) is glycopyrronium bromide.

7. The pharmaceutical composition of claim 1 , wherein the drug component includes at least one corticosteroid.

8. The pharmaceutical composition of claim 7 , wherein the at least one corticosteroid is selected from fluticasone and the pharmaceutically acceptable salts and esters thereof.

9. The pharmaceutical composition of claim 8 , wherein the at least one corticosteroid is fluticasone propionate.

10. The pharmaceutical composition of claim 9 , wherein the drug component comprises a binary mixture of fluticasone propionate and salmeterol xinafoate.

11. A pharmaceutical composition 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 consisting of one or more hydrofluorocarbon and hydrocarbon propellant compounds, where at least 90 wt % of the propellant component is 1,1-difluoroethane (HFA-152a),
wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.

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

13. The pharmaceutical composition of claim 1 , wherein the polar excipient is ethanol.

14. 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 stabilisers; (iv) pharmaceutically acceptable salts of both cromoglycic acid and nedocromil; (v) polar excipients; and (vi) ethanol.

15. The pharmaceutical composition of claim 1 which after storage in uncoated aluminium 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.

16. The pharmaceutical composition of claim 15 , 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 aluminium containers at 40° C. and 75% relative humidity for 6 months.

17. The pharmaceutical composition of claim 1 which when delivered from a metered dose inhaler yields a fine particle fraction of the at least one salmeterol compound which is at least 42.5 weight % of the emitted dose of the at least one salmeterol compound.

18. The pharmaceutical composition of claim 1 in the form of a suspension.

19. The pharmaceutical composition of claim 1 in the form of a solution.

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

21. The pharmaceutical composition of claim 1 , wherein the one or more hydrofluorocarbon and hydrocarbon propellant compounds are selected from the group consisting of 1,1-difluoroethane (HFA-152a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea), 1,1,1,2-tetrafluoroethane (HFA-134a), difluoromethane (HFA-32), propane, butane, isobutane and dimethyl ether.

22. The pharmaceutical composition of claim 21 , wherein the one or more hydrofluorocarbon and hydrocarbon propellant compounds are selected from the group consisting of 1,1-difluoroethane (HFA-152a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) and 1,1,1,2-tetrafluoroethane (HFA-134a).

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

• A61K47/14

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

• A61K47/24

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

• A61K9/124

  characterised by the propellant · CPC title

• A61K31/137 Primary

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title