Canister containing aerosol formulations containing P134a and particulate medicaments

• US 5,817,293 A
• Filed: 05/30/1995
• Issued: 10/06/1998
• 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:
  US08/453,760
• Time in Patent Office: 1,225 Days
• Field of Search: 424/45, 424/47, 424/46, 222/402.1
• 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 31/167 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 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• 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 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• 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: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

This invention relates to a canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve and contains a pharmaceutical aerosol formulation for inhalation therapy consisting essentially of a physiologically effective amount of particulate medicament, 1,1,1,2-tetrafluoroethane as propellant and up to 5% w/w based upon propellant of a polar co-solvent, which formulation is substantially free of surfactant.

Claims

1. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve, and contains a pharmaceutical aerosol formulation consisting essentially of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent which is a C_2-6 aliphatic alcohol or polyol or a mixture thereof, 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, and which formulation contains less than 0.0001 % w/w surfactant based upon the weight of medicament.

2. A canister as claimed in claim 1 wherein the polar cosolvent is present in an amount from 0.05 to 3% w/w based upon the propellant.

3. A canister as claimed in claim 2 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid.

4. A canister as claimed in claim 2 wherein said medicament is selected from the group consisting of salmeterol, salbutamol, fluticasone propionate, and physiologically acceptable salts and solvates thereof.

5. A canister as claimed in claim 2 wherein said medicament is beclomethasone dipropionate or a physiologically acceptable solvate thereof.

6. A canister as claimed in claim 2 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tolubuterol, orciprenaline, (-)-4-amino-3,5-dichloro-α

- 6- 2-(2-pyridinyl)ethoxy!hexyl!-amino!methyl!benzene-methanol and physiologically acceptable salts thereof.

7. A canister as claimed in claim 2 wherein the formulation contains two or more particulate medicaments.

8. A canister as claimed in claim 2 wherein the formulation contains a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament.

9. A canister as claimed in claim 2 wherein the formulation contains salmeterol xinafoate in combination with fluticasone propionate.

10. A canister as claimed in claim 2 wherein the formulation is free of surfactant.

11. A canister as claimed in claim 2 wherein the polar cosolvent is ethanol.

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

13. A canister as claimed in claim 2 wherein the formulation has a respirable fraction of 20% or more by weight of the medicament.

26. A canister as claimed in claim 2 wherein the polar cosolvent is ethanol.

39. A canister as claimed in claim 1 wherein the polar cosolvent is present in an amount of 0.05 to 5% w/w based upon the propellant.

44. A canister as claimed in claim 2 wherein said medicament is an antiallergic medicament selected from the group consisting of cromoglycate, ketotifen, nedocromil, and physiologically acceptable salts thereof.

45. A canister as claimed in claim 2 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide.

46. A canister as claimed in claim 2 wherein said medicament is an anticholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof.

47. A canister as claimed in claim 2 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline, and physiologically acceptable salts thereof.

14. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve, and contains a pharmaceutical aerosol formulation consisting of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent which is C_2-6 aliphatic alcohol or polyol or a mixture thereof, 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.

15. A canister as claimed in claim 14 wherein the polar cosolvent is present in an amount from 0.05 to 3% w/w based upon the propellant.

16. A canister as claimed in claim 15 wherein said medicament is selected from the group consisting of salmeterol, salbutamol, fluticasone propionate, and physiologically acceptable salts and solvates thereof.

17. A canister as claimed in claim 15 wherein said medicament is beclomethasone dipropionate or a physiologically acceptable solvate thereof.

18. A canister as claimed in claim 15 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, orciprenaline, (-)-4-amino-3,5-dichloro-α

6- 2-2(-pyridinyl)ethoxy!hexyl!-amino!methyl!benzene-methanol and physiologically acceptable salts thereof.

19. A canister as claimed in claim 15 wherein the formulation contains two or more particulate medicaments.

20. A canister as claimed in claim 15 wherein the formulation contains a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament.

21. A canister as claimed in claim 15 wherein the formulation contains salmeterol xinafoate in combination with fluticasone propionate.

22. A canister as claimed in claim 15 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid.

23. A canister as claimed in claim 15 wherein the polar cosolvent is ethanol.

24. A canister as claimed in claim 15 wherein the medicament is present in an amount from 0.01 to 1 % w/w relative to the total weight of the formulation.

25. A canister as claimed in claim 15 wherein the formulation has a respirable fraction of 20% or more by weight of the medicament.

27. A canister as claimed in claim 22 wherein the polar cosolvent is ethanol.

48. A canister as claimed in claim 15 wherein said medicament is an antiallergic medicament selected from the group consisting of cromoglycate, ketotifen, nedocromil, and physiologically acceptable salts thereof.

49. A canister as claimed in claim 15 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide.

50. A canister as claimed in claim 15 wherein said medicament is an anticholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof.

51. A canister as claimed in claim 15 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline, and physiologically acceptable salts thereof.

28. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve, and contains a pharmaceutical aerosol formulation consisting essentially of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane as propellant and (iii) 0.05 to 5% w/w based upon the propellant of a polar cosolvent being ethanol, isopropanol, propylene glycol or a mixture thereof, the particulate medicament being present in an amount from 0.01 to 1% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns, and which formulation contains less than 0.0001 % w/w surfactant based upon the weight of medicament.

29. A canister as claimed in claim 28 wherein the formulation is free of surfactant.

30. A canister as claimed in claim 28 wherein the formulation contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent.

31. A canister as claimed in claim 29 wherein the formulation contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent.

32. A canister as claimed in claim 28 wherein the polar cosolvent is ethanol.

33. A canister as claimed in claim 29 wherein the polar cosolvent is ethanol.

34. A canister as claimed in claim 28 wherein said medicament is formoterol or a physiologically acceptable salt thereof.

35. A canister as claimed in claim 29 wherein said medicament is formoterol or a physiologically acceptable salt thereof.

36. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve, and contains a pharmaceutical aerosol formulation consisting of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane as propellant and (iii) 0.05 to 5% w/w based upon the propellant of a polar cosolvent being ethanol, isopropanol, propylene glycol or a mixture thereof, the particulate medicament being present in an amount from 0.01 to 1 % w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

37. A canister as claimed in claim 36 wherein the formulation contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent.

38. A canister as claimed in claim 36 wherein the polar cosolvent is ethanol.

40. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy including a propellant which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve, and contains a pharmaceutical aerosol formulation consisting of(i) a particulate medicament which is salmeterol or physiologically acceptable salts thereof, (ii) 1,1,1,2-tetrafluoroethane as propellant and (iii) 0.05 to 5% w/w based upon the propellant of a polar cosolvent being ethanol, isopropanol, propylene glycol or a mixture thereof, the particulate medicament being present in an amount from 0.01 to 1 % w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

41. A canister as claimed in claim 40 wherein the polar cosolvent is ethanol.

42. A canister as claimed in claim 40 wherein the salmeterol is in the form of salmeterol xinafoate.

43. A canister as claimed in claim 42 wherein the polar cosolvent is ethanol.