Aerosol formulations containing propellant 134a and fluticasone propionate

• US 5,658,549 A
• Filed: 05/19/1995
• Issued: 08/19/1997
• Est. Priority Date: 12/12/1991
• Status: Expired due to Term

• Current Assignee: Glaxo Group Limited (GSK plc)
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Wyatt, David Andrew, Taylor, Anthony James, Akehurst, Rachel Ann
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/444,925
• Time in Patent Office: 823 Days
• Field of Search: 424/45, 424/47
• US Class Current: 424/45
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]

Abstract

This invention relates to aerosol formulations of use for the administration of medicaments by inhalation, in particular a pharmaceutical aerosol formulation which comprises particulate medicament selected from the group comprising salmeterol, salbutamol, fluticasone propionate and physiologically acceptable salts and solvates thereof and a fluorocarbon or hydrogen-containing chlorofluorocarbon propellant, which formulation is substantially free of surfactant. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as defined is also described.

Claims

1. A pharmaceutical aerosol formulation consisting essentially of particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof, and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of medicament, the particulate medicament being present in an amount from 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

2. A formulation as claimed in claim 1 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

3. A formulation as claimed in claim 1 which has a respirable fraction of 20% or more by weight of the particulate medicament.

4. A pharmaceutical aerosol formulation consisting essentially of particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof, and 1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant, the particulate medicament being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

6. A formulation as claimed in claim 4 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

8. A formulation as claimed in claim 4 which has a respirable fraction of 20% or more by weight of the particulate medicament.

5. A pharmaceutical aerosol formulation consisting of particulate medicament consisting of fluticasone propionate or a physiologically acceptable solvate thereof, and 1,1,1,2-tetrafluoroethane as propellant, the particulate medicament being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

7. A formulation as claimed in claim 5 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

9. A formulation as claimed in claim 5 which has a respirable fraction of 20% or more by weight of the particulate medicament.

10. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof;

a particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant, the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns which formulation is free of surfactant.

12. A formulation as claimed in claim 10 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

14. A formulation as claimed in claim 10 which has a respirable fraction of 20% or more by weight of the particulate medicaments.

16. A formulation as claimed in claim 10 which contains fluticasone propionate or a physiologically acceptable solvate thereof and salmeterol or salbutamol or a physiologically acceptable salt thereof.

18. A formulation as claimed in claim 10 which contains fluticasone propionate and salmeterol xinafoate.

11. A pharmaceutical aerosol formulation consisting of particulate medicament consisting of fluticasone propionate or a physiologically acceptable solvate thereof;

particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant, the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

13. A formulation as claimed in claim 11 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

15. A formulation as claimed in claim 11 which has a respirable fraction of 20% or more by weight of the particulate medicaments.

17. A formulation as claimed in claim 11 which contains fluticasone propionate or a physiologically acceptable solvate thereof and salmeterol or salbutamol or a physiologically acceptable salt thereof.

19. A formulation as claimed in claim 11 which contains fluticasone propionate and salmeterol xinafoate.

20. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof;

a particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate, mixtures thereof and physiologically acceptable salts and solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of medicaments, the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

21. A formulation as claimed in claim 20 which contains fluticasone propionate and salmeterol xinafoate.

34. A formulation as claimed in claim 20 wherein the particulate medicaments are present in an amount of 0.01% to 1% w/w relative to the total weight of the formulation.

35. A formulation as claimed in claim 20 which has a respirable fraction of 20% or more by weight of the particulate medicaments.

22. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting essentially of particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof, and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based on the weight of medicament, the particulate medicament being present in an amount from 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

23. A method as claimed in claim 22 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

24. A method as claimed in claim 22 which has a respirable fraction of 20% or more by weight of the particulate medicament.

25. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting of particulate medicament consisting of fluticasone propionate or a physiologically acceptable solvate thereof, and 1,1,1,2-tetrafluoroethane as propellant, the particulate medicament being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

26. A method as claimed in claim 25 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

27. A method as claimed in claim 25 which has a respirable fraction of 20% or more by weight of the particulate medicament.

28. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting essentially of particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof;

a particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant which formulation contains less than 0.0001% w/w surfactant based on the weight of medicament the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

29. A method as claimed in claim 28 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

30. A method as claimed in claim 28 which contains fluticasone propionate and salmeterol xinafoate.

31. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting of particulate medicament consisting of fluticasone propionate or a physiologically acceptable solvate thereof;

a particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant, the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

32. A method as claimed in claim 31 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

33. A method as claimed in claim 32 which contains fluticasone propionate and salmeterol xinafoate.

36. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is fluticasone propionate or a physiologically acceptable solvate thereof;

and 1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant, the particulate medicament being present in an amount from 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

37. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is fluticasone propionate or physiologically acceptable solvate thereof;

particulate medicament selected from the group consisting of salmeterol, salbutamol, beclomethasone dipropionate and physiologically acceptable salts or solvates thereof; and

1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant, the particulate medicaments being present in an amount of 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

38. A method as claimed in claim 37 wherein the particulate medicaments are fluticasone propionate and salmeterol xinafoate.

39. A method as claimed in claim 38 wherein the particulate medicaments are present in an amount of from 0.01 to 1% w/w relative to the total weight of the formulation.