Details for Patent: 5,916,540
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| Title: | Aerosol formulations containing P134A and/or P227 and particulate medicament |
| Abstract: | A pharmaceutical aerosol formulation comprising (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture thereof as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent, 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. |
| Inventor(s): | Akehurst; Rachel Ann (Ware, GB), Taylor; Anthony James (Ware, GB), Wyatt; David Andrew (Ware, GB) |
| Assignee: | Glaxo Group Limited (Middlesex, GB) |
| Filing Date: | Apr 06, 1998 |
| Application Number: | 09/055,253 |
| Claims: | 1. A pharmaceutical aerosol formulation consisting essentially of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture thereof as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent, 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 formulation 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 formulation 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. 4. A formulation as claimed in claim 2 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid. 5. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof. 6. A formulation as claimed in claim 2 wherein said medicament is beclomethasone dipropionate or a physiologically acceptable solvate thereof. 7. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, rimiterol, terbutaline, (-)4-amino-3,5-dichloro-.alpha.-[[[6-[2-(2-pyridinyl)ethoxy]h exyl]-amino]methyl]benzene-methanol and physiologically acceptable salts thereof. 8. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of pirbuterol and physiologically acceptable salts thereof. 9. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of formoterol and physiologically acceptable salts thereof. 10. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of fenoterol, reproterol, isoetharine and tolubuterol. 11. A formulation as claimed in claim 2 which contains two or more particulate medicaments. 12. A formulation as claimed in claim 2 which contains a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament. 13. A formulation as claimed in claim 2 which contains salmeterol xinafoate in combination with fluticasone propionate. 14. A formulation as claimed in claim 2 which is free of surfactant. 15. A formulation 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. 16. A formulation as claimed in claim 2 which has a respirable fraction of 20% or more by weight of the medicament. 17. A formulation as claimed in claim 2 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen, nedocromil and physiologically acceptable salts thereof. 18. A formulation as claimed in claim 2 wherein said medicament is selected from the group consisting of cromoglycate and physiologically acceptable salts thereof. 19. A formulation as claimed in claim 2 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide. 20. A formulation as claimed in claim 2 wherein said medicament is flunisolide. 21. A formulation as claimed in claim 2 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof. 22. A formulation 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. 23. A pharmaceutical aerosol formulation consisting of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture thereof as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent, 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. 24. A formulation as claimed in claim 23 wherein the polar cosolvent is present in an amount from 0.05 to 3% w/w based upon the propellant. 25. A formulation as claimed in claim 24 wherein said medicament is selected from the group consisting of salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof. 26. A formulation as claimed in claim 24 wherein said medicament is beclomethasone dipropionate or a physiologically acceptable solvate thereof. 27. A formulation as claimed in claim 24 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, rimiterol, terbutaline, orciprenaline, (-)4-amino-3,5-dichloro-.alpha.-[[[6-[2-2(-pyridinyl)ethoxy]hexyl]-amino]m ethyl]benzene-methanol and physiologically acceptable salts thereof. 28. A formulation as claimed in claim 24 wherein said medicament is selected from the group consisting of pirbuterol and physiologically acceptable salts thereof. 29. A formulation as claimed in claim 24 wherein said medicament is selected from the group consisting of formoterol and physiologically acceptable salts thereof. 30. A formulation as claimed in claim 24 wherein said medicament is selected from the group consisting of fenoterol, reproterol, isoetharine and tolubuterol. 31. A formulation as claimed in claim 24 which contains two or more particulate medicaments. 32. A formulation as claimed in claim 24, which contains a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament. 33. A formulation as claimed in claim 24, which contains salmeterol xinafoate in combination with fluticasone propionate. 34. A formulation as claimed in claim 24 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid. 35. A formulation as claimed in claim 24 wherein the medicament is present in an amount from 0.01 to 1% w/w relative to the total weight of the formulation. 36. A formulation as claimed in claim 24 which has a respirable fraction of 20% or more by weight of the medicament. 37. A formulation as claimed in claim 24 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen, nedocromil and physiologically acceptable salts thereof. 38. A formulation as claimed in claim 24 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide. 39. A formulation as claimed in claim 24 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof. 40. A formulation as claimed in claim 24 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline and physiologically acceptable salts thereof. 41. A pharmaceutical aerosol formulation consisting essentially of (I) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture thereof as propellant and (iii) 0.05 to 5% w/w based upon the propellant of a polar cosolvent, 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. 42. A formulation as claimed in claim 41 which is free of surfactant. 43. A formulation as claimed in claim 41 which contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent. 44. A formulation as claimed in claim 42 which contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent. 45. A formulation as claimed in claim 42 wherein said medicament is flunisolide. 46. A formulation as claimed in claim 42 wherein said medicament is formoterol or a physiologically acceptable salt thereof. 47. A formulation as claimed in claim 42 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, rimiterol, terbutaline, (-)-4-amino-3,5-dichloro-.alpha.-[[[6-[2-(2-pyridinyl)ethoxy] hexyl]-amino]methyl]benzene-methanol and physiologically acceptable salts thereof. 48. A formulation as claimed in claim 42 wherein said medicament is selected from the group consisting of pirbuterol and physiologically acceptable salts thereof. 49. A formulation as claimed in claim 42 wherein said medicament is selected from the group consisting of fenoterol, reproterol, isoetharine and tolubuterol. 50. A formulation as claimed in claim 42 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen or nedocromil and physiologically acceptable salts thereof. 51. A formulation as claimed in claim 42 wherein said medicament is selected from the group consisting of cromoglycate and physiologically acceptable salts thereof. 52. A formulation as claimed in claim 42 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide. 53. A formulation as claimed in claim 42 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof. 54. A formulation as claimed in claim 42 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline and physiologically acceptable salts thereof. 55. A pharmaceutical aerosol formulation consisting of (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture as propellant and (iii) 0.05 to 5% w/w based upon the propellant of a polar cosolvent, 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. 56. A formulation as claimed in claim 55 which contains 0.05 to 3% w/w based upon the propellant of a polar cosolvent. 57. A formulation as claimed in claim 56 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen, nedocromil and physiologically acceptable salts thereof. 58. A formulation as claimed in claim 56 wherein said medicament is selected from the group consisting of cromoglycate and physiologically acceptable salts thereof. 59. A formulation as claimed in claim 56 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide. 60. A formulation as claimed in claim 56 wherein said medicament is flunisolide. 61. A formulation as claimed in claim 56 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium, and physiologically acceptable salts thereof. 62. A formulation as claimed in claim 56 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline and physiologically acceptable salts thereof. 63. A formulation as claimed in claim 56 wherein said medicament is selected from the group consisting of ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tolubuterol, (-)4-amino-3,5-dichloro-.alpha.-[[[6-[2-(2-pyridinyl)ethoxy]hexyl]-amino]m ethyl]benzene-methanol and physiologically acceptable salts thereof. 64. A pharmaceutical aerosol formulation consisting of (i) a particulate medicament which is triamcinalone acetonide (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture as propellant and (iii) 0.05 to 3% w/w based upon the propellant of a polar cosolvent, 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. 65. A formulation as claimed in claim 64 wherein the polar cosolvent is ethanol. 66. A formulation as claimed in claim 64 wherein the propellant is 1,1,1,2-tetrafluoroethane. 67. A formulation as claimed in claim 65 wherein the propellant is 1,1,1,2-tetrafluoroethane. 68. A pharmaceutical aerosol formulation comprising (i) particulate medicament, (ii) 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3,-heptafluoro-n-propane or a mixture as propellant, and (iii) 0.01 to 5% w/w based upon the propellant of a polar cosolvent, 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. 69. A formulation as claimed in claimed 68 wherein the polar cosolvent is present in an amount of from 0.05% to 3% w/w based upon the propellant. 70. A formulation as claimed in claim 68 wherein the polar cosolvent is present in an amount from 0.05% to 5% w/w based upon the propellant. 71. A formulation as claimed in claim 70 wherein the polar cosolvent is ethanol. 72. A formulation as claimed in claim 70 wherein the medicament is formoterol or a physiologically acceptable salt thereof. 73. A formulation as claimed in claim 69 wherein the medicament is formoterol or a physiologically acceptable salt thereof. 74. A formulation as claimed in claim 73 wherein the polar cosolvent is ethanol. 75. A formulation as claimed in claim 9 wherein the polar cosolvent is ethanol. 76. A formulation as claimed in claim 29 wherein the polar cosolvent is ethanol. 77. A formulation as claimed in claim 46 wherein the polar cosolvent is ethanol. 78. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as claimed in claim 1. 79. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as claimed in claim 23. 80. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as claimed in claim 41. 81. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as claimed in claim 55. 82. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as claimed in claim 9. 83. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 68. 84. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 2. 85. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 24. 86. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 43. 87. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 56. 88. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 65. 89. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 46. 90. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 69. 91. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as a claimed in claim 74. 92. A formulation as claimed in claim 1 wherein the polar cosolvent is ethanol. 93. A formulation as claimed in claim 23 wherein the polar cosolvent is ethanol. 94. A formulation as claimed in claim 41 wherein the polar cosolvent is ethanol. 95. A formulation as claimed in claim 35 wherein the polar cosolvent is ethanol. 96. A formulation as claimed in claim 1 wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n-propane. 97. A formulation as claimed in claim 23 wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n-propane. 98. A formulation as claimed in claim 41 wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n-propane. 99. A formulation as claimed in claim 55 wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n-propane. 100. A formulation as claimed in claim 68 wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n-propane. 101. A formulation as claimed in claim 64 wherein the propellant is 1,1,1,2,3,3,3-heptafluoro-n-propane. 102. A formulation as claimed in claim 68 wherein the propellant is 1,1,1,2,3,3,3-heptafluoro-n-propane. |
