Aerosol formulations containing P134a and particulate medicament

• US 6,893,628 B2
• Filed: 03/31/2003
• Issued: 05/17/2005
• Est. Priority Date: 12/12/1991
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Wyatt, David Andrew, Akehurst, Rachel Ann, Taylor, Anthony James
• Primary Examiner(s): Dodson, Shelley A.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/401,722
• Publication Number:
  US 20030165437A1
• Time in Patent Office: 778 Days
• Field of Search: 424/400, 424/45, 424/46, 424/489, 514/826, 514/958
• 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 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• 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
• CPC Class Codes: A61K 9/145 : with organic compounds
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 11/08 : Bronchodilators

Abstract

A pharmaceutical formulation comprising (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafuoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of medicament, particulate medicament being present in an amount from 00005 to 5% 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 medicament is other than salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate or a physiologically acceptable salt or solvate thereof and with the proviso that when the formulation consists of betamethasone, ergotamine tartrate or sodium cromoglycate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69:7900 or 0.866% w/w.

Claims

1. A pharmaceutical aerosol formulation comprising a particulate medicament which is budesonide and 1,1,1,2-tetrafluoroethane as propellant, which formulation is substantially free of surfactant, is substantially free of chlorofluorocarbons and is free of alcohols and wherein the medicament is present in an amount of 0.01-1% w/w relative to the total weight of the formulation.

2. A formulation as claimed in claim 1 wherein said formulation contains two or more particulate medicaments.

3. A formulation as claimed in claim 2 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory steroid medicament.

11. A formulation as claimed in claim 2 which comprises particulate budesonide in combination with particulate formoterol or a physiologically acceptable salt thereof.

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

17. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 1.

18. A method according to claim 17 wherein the respiratory disorder is asthma.

19. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 3.

20. A method according to claim 19 wherein the respiratory disorder is asthma.

33. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 11.

34. A method according to claim 33 wherein the respiratory disorder is asthma.

37. A formulation as claimed in claim 1 which is free of ethanol.

38. A method of treatment of asthma which comprises administration by inhalation of an effective amount of a formulation according to claim 37.

39. A formulation as claimed in claim 3 which is free of ethanol.

40. A method of treatment of asthma which comprises administration by inhalation of an effective amount of a formulation according to claim 39.

41. A formulation as claimed in claim 11 which is free of ethanol.

42. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 41.

43. A method according to claim 42 wherein the respiratory disorder is asthma.

4. A pharmaceutical aerosol formulation consisting essentially of particulate medicament which is budesonide optionally in combination with a particulate anti-inflammatory steroid medicament and 1,1,1,2-tetrafluoroethane as propellant which formulation is substantially free of surfactant and wherein the medicament is present in an amount of 0.01-1% w/w relative to the total weight of the formulation.

6. A pharmaceutical aerosol formulation as claimed in claim 4 consisting essentially of particulate medicament which is budesonide and 1,1,1,2-tetrafluoroethane as propellant wherein the medicaments present in an amount of 0.01-1% w/w relative to the total weight of the formulation.

7. A formulation as claimed in claim 4 wherein said formulation contains two or more particulate medicaments.

9. A formulation as claimed in claim 7 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory steroid medicament.

12. A formulation as claimed in claim 7 which comprises particulate budesonidein combination with particulate formoterol or a physiologically acceptable salt thereof.

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

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

21. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 4.

22. A method according to claim 21 wherein the respiratory disorder is asthma.

25. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 6.

26. A method according to claim 25 wherein the respiratory disorder is asthma.

28. A method according to claim 25 wherein the respiratory disorder is asthma.

29. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 9.

30. A method according to claim 29 wherein the respiratory disorder is asthma.

35. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 12.

36. A method according to claim 35 wherein the respiratory disorder is asthma.

5. A pharmaceutical aerosol formulation consisting of particulate medicament which is budesonide optionally in combination with other medicaments and 1,1,1,2-tetrafluoroethane as propellant wherein the medicament is present in an amount of 0.01-1% w/w relative to the total weight of the formulation.

8. A formulation as claimed in claim 5 wherein said formulation contains two or more particulate medicaments.

10. A formulation as claimed in claim 8 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory steroid medicament.

13. A formulation as claimed in claim 8 which comprises particulate budesonide in combination with particulate formoterol or a physiologically acceptable salt thereof.

23. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 5.

24. A method according to claim 23 wherein the respiratory disorder is asthma.

27. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 13.

31. A method of treatment of respiratory disorders which comprises administration by inhalation of an effective amount of a formulation according to claim 10.

32. A method according to claim 31 wherein the respiratory disorder is asthma.