Aerosol formulations containing P134a and salbutamol

• US 5,674,471 A
• Filed: 05/19/1995
• Issued: 10/07/1997
• 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:
  US08/444,725
• Time in Patent Office: 872 Days
• Field of Search: 424/45, 424/47, 424/46, 514/826
• 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]
• CPC Class Codes: A61K 9/124 characterised by the propellant

Abstract

The invention relates to a pharmaceutical aerosol formulation consisting essentially of particulate medicament which is salbutamol or a physiologically acceptable salt or solvate thereof and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% surfactant based upon the weight of medicament, 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, with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:18, said salbutamol is present in the form of a physiologically acceptable salt and when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69:7900 or 0.866%.

Claims

1. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or solvate thereof and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% surfactant based upon the weight of medicament, 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, with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt and when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.866%.

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 particulate medicament.

4. A formulation as claimed in claim 1 wherein the salbutamol is in the form of its sulphate salt.

30. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 1.

31. A method as claimed in claim 30 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

32. A method as claimed in claim 30 wherein the formulation has a respirable fraction of 20% or more by weight of particulate medicament.

33. A method as claimed in claim 30 wherein the salbutamol is in the form of its sulphate salt.

5. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is in the form of a physiologically acceptable salt and when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.0866%.

6. 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.

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

8. A formulation as claimed in claim 5 wherein the salbutamol is in the form of its sulphate salt.

34. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 5.

35. A method as claimed in claim 34 wherein the salbutamol is in the form of its sulphate salt.

36. A method as claimed in claim 34 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 pharmaceutical aerosol formulation consisting of a particulate medicament which is salbutamol or a physiologically acceptable salt or solvate thereof and 1,1,1,2-tetrafluoroethene 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, with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt and when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.866%.

10. A formulation as claimed in claim 9 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

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

12. A formulation as claimed in claim 9 wherein the salbutamol is in the form of its sulphate salt.

37. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 9.

38. A method as claimed in claim 37 wherein the particulate medicament is present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

39. A method as claimed in claim 37 wherein the formulation has a respirable fraction of 20% or more by weight of particulate medicament.

40. A method as claimed in claim 37 wherein the salbutamol is in the form of its sulphate salt.

13. A pharmaceutical aerosol formulation consisting essentially of the particulate medicaments salbutamol and beclomethasone dipropionate, or physiologically acceptable salts or 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 particulate 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.

14. A formulation as claimed in claim 13 wherein the salbutamol is in the form of its sulphate salt.

15. A formulation as claimed in claim 13 which formulation is free of surfactant.

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

41. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 13.

42. A method as claimed in claim 41 wherein the formulation has a respirable fraction of 20% or more by weight of particulate medicament.

43. A method as claimed in claim 41 wherein the salbutamol is in the form of its sulphate salt.

44. A method as claimed in claim 41 which formulation is free of surfactant.

45. A method as claimed in claim 41 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

17. A pharmaceutical aerosol formulation consisting of the particulate medicaments salbutamol and beclomethasone dipropionate, or physiologically acceptable salts or solvates thereof, and 1,1,1,2-tetrafluoroethane as propellant, the particulate medicaments 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.

18. A formulation as claimed in claim 17 wherein the salbutamol is in the form of its sulphate salt.

19. A formulation as claimed in claim 17 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

46. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 17.

47. A method as claimed in claim 46 wherein the formulation has a respirable fraction of 20% or more by weight of particulate medicament.

48. A method as claimed in claim 46 wherein the salbutamol is in the form of its sulphate salt.

49. A method as claimed in claim 46 wherein the particulate medicaments are present in an amount of 0.01 to 1% w/w relative to the total weight of the formulation.

20. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, and wherein the salbutamol or a physiologically acceptable salt or solvate there is present in an amount of less than 0.866% w/w based on the total weight of the formulation, with the proviso that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt.

25. A formulation as claimed in claim 20 wherein the salbutamol is in the form of its sulphate salt.

21. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, and wherein the salbutamol or a physiologically acceptable salt or solvate thereof is present in an amount of 0.005 to 0.594% w/w based on the total weight of the formulation, with the proviso that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt.

26. A formulation as claimed in claim 21 wherein the salbutamol is in the form of its sulphate salt.

22. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, and wherein the salbutamol or a physiologically acceptable salt or solvate thereof is present in an amount of 0.005 to 0.264% w/w based on the total weight of the formulation.

27. A formulation as claimed in claim 22 wherein the salbutamol is in the form of its sulphate salt.

23. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, and wherein the salbutamol or a physiologically acceptable salt or solvate thereof is present in an amount of 0.005 to 0.174% w/w based on the total weight of the formulation.

28. A formulation as claimed in claim 23 wherein the salbutamol is in the form of its sulphate salt.

24. A pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or 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, which formulation is free of surfactant, and wherein the weight ratio of salbutamol or a pharmaceutically acceptable or solvate thereof to propellant is less than 0.05:

18.

29. A formulation as claimed in claim 24, wherein the salbutamol is in the form of its sulphate salt.

50. A pharmaceutical aerosol formulation consisting of a particulate medicament which is salbutamol sulphate and 1,1,1,2-tetrafluoroethane as propellant, the particulate medicament being present in an amount of 0.01% to 1% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns, with the proviso that the weight to weight ratio of medicament to propellant is other than 69:

7900 or 0.866%.

51. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation of claim 50.