초록

Aerosol formulations suitable for use in pressurised metered dose inhalers comprise a hydrofluoroalkane propellant, an medicament for inhalation and a surfactant which is a a C8?C16 fatty acid or salt thereof, a bile salt, a phospholipid, or an alkyl saccharide.

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1. A pharmaceutical aerosol formulation comprising a hydrofluoroalkane (HFA) propellant; a physiologically effective amount of a medicament for inhalation; and an alkyl saccharide surfactant, wherein the medicament and the surfactant are suspended in the propellant as a finely divided powder.2. A ph

1. A pharmaceutical aerosol formulation comprising a hydrofluoroalkane (HFA) propellant; a physiologically effective amount of a medicament for inhalation; and an alkyl saccharide surfactant, wherein the medicament and the surfactant are suspended in the propellant as a finely divided powder.2. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the surfactant is selected from the group consisting of an alkyl glucoside and an alkyl maltoside.3. A pharmaceutical aerosol formulation as claimed in claim 2, wherein the surfactant is selected from the group consisting of decyl glucoside and dodecyl maltoside.4. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the formulation comprises a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227), or 1,1-difluoroethane (P152a).5. The pharmaceutical aerosol formulation as claimed in claim 4, wherein the surfactant is decyl glucoside.6. The pharmaceutical aerosol formulation as claimed in claim 4, wherein the surfactant is dodecyl maltoside.7. A pharmaceutical aerosol formulation as claimed in claim 4, wherein the formulation comprises a propellant mixture comprising 1,1,1,2-tetrafluoroethane (P134a) and 1,1,1,2,3,3,3-heptafluoropropane (P227).8. A pharmaceutical aerosol formulation as claimed in claim 7, wherein the formulation comprises a density-matched propellant mixture of 1,1,1,2-tetrafluoroethane (P134a) and 1,1,1,2,3,3,3-heptafluoropropane (P227).9. The pharmaceutical aerosol formulation as claimed in claim 7, wherein the surfactant is decyl glucoside.10. The pharmaceutical aerosol formulation as claimed in claim 7, wherein the surfactant is dodecyl maltoside.11. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the medicament is selected from the group consisting of a β2-adrenoreceptor agonist, an anticholinergic bronchodilator, and a glucocorticosteroid.12. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the medicament is selected from the group consisting of salbutamol, terbutaline, rimiterol, fenoterol, reproterol, adrenaline, pirbuterol, isoprenaline, orciprenaline, bitolterol, salmeterol, formoterol, clenbuterol, procaterol, broxaterol, picumeterol, mabuterol, ipratropium bromide, beclomethasone, fluticasone, budesonide, tipredane, dexamethasone, betamethasone, fluocinolone, triamcinolone acetonide, mometasone, and pharmacologically acceptable esters and salts thereof.13. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the medicament is selected from the group consisting of anti-allergic medicaments, expectorants, mucolytics, antihistamines, cyclooxygenase inhibitors, leukotriene synthesis inhibitors, leukotriene antagonists, phospholipase-A2 (PLA2) inhibitors, platelet aggregating factor (PAF) antagonists, prophylactics of asthma, antiarrhythmic medicaments, tranquilisers, cardiac glycosides, hormones, anti-hypertensive medicaments, antidiabetic medicaments, antiparasitic medicaments, anticancer medicaments, sedatives, analgesic medicaments, antibiotics, antirheumatic medicaments, immunotherapeutic agents, antifungal medicaments, antihypotension medicaments, vaccines, antiviral medicaments, proteins, peptides, vitamins, cell surface receptor blockers, antioxidants, free radical scavengers, and organic salts of N,N′-diacetylcystine.14. A pharmaceutical aerosol formulation as claimed in claim 1, including ethanol in an amount of up to 20% by weight of propellant and surfactant.15. A pharmaceutical aerosol formulation as claimed in claim 1, including ethanol in an amount of up to 5% by weight of propellant and surfactant.16. A pharmaceutical aerosol formulation as claimed in claim 1, further comprising a substance selected from the group consisting of adjuvants, carriers, flavouring agents, buffers, antioxidants and chemical stabilisers.17. A pharmaceutical aerosol formulation as claimed in claim 1, wherein at least 50% of the medicament consists of particles having a diameter of 0.01?10 microns.18. A pharmaceutical aerosol formulation as claimed in claim 17, wherein at least 70% of the medicament consists of particles having a diameter of 0.01?10 microns.19. A pharmaceutical aerosol formulation as claimed in claim 17, wherein at least 90% of the medicament consists of particles having a diameter of 0.01?10 microns.20. A pharmaceutical aerosol formulation as claimed in claim 1, wherein at least 50% of the medicament consists of particles having a diameter of 0.1?6 microns.21. A pharmaceutical aerosol formulation as claimed in claim 20, wherein at least 70% of the medicament consists of particles having a diameter of 0.01?6 microns.22. A pharmaceutical aerosol formulation as claimed in claim 20, wherein at least 90% of the medicament consists of particles having a diameter of 0.01?6 microns.23. A pharmaceutical aerosol formulation as claimed in claim 1, wherein at least 50% of the medicament consists of particles having a diameter of 0.1?5 microns.24. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the concentration of medicament in the formulation is 0.1 mg/ml to 25 mg/ml.25. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the ratio of surfactant to medicament is in the range of 1:50 to 1:0.2.26. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of a β2-adrenoreceptor agonist and a glucocorticosteriod.27. A pharmaceutical aerosol formulation as claimed in claim 26, further comprising a physiologically effective amount of an anticholinergic bronchodilator.28. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) budesonide, or a salt, ester, solvate, or solvate of a salt or ester thereof.29. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) mometasone, or a salt ester, solvate, or solvate of a salt or ester therefor.30. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) fluticasone, or a salt, ester, solvate, or solvate of a salt or ester thereof.31. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of (a) salmeterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) fluticasone, or a salt, ester, solvate, or solvate of a salt or ester thereof.32. The pharmaceutical aerosol formulation as claimed in claim 1, wherein the surfactant is decyl glucoside.33. The pharmaceutical aerosol formulation as claimed in claim 1, wherein the surfactant is dodecyl maltoside.34. A pharmaceutical aerosol formulation as claimed in claim 1, the formulation comprising a physiologically effective amount of each of (a) formoterol and (b) budesonide.35. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the formulation comprises a physiologically effective amount of each of (a) an anticholinergic bronchodilator and (b) a β2-adrenoreceptor agonist.36. A pharmaceutical aerosol formulation as claimed in claim 1, wherein the formulation comprises a physiologically effective amount of each of (a) an anticholinergic bronchodilator and (b) a glucocorticosteroid.37. A method for the manufacture of a pharmaceutical aerosol formulation as claimed in claim 1, comprising the steps of:providing a mixture of the medicament and the surfactant in a vessel;adding hydrofluoroalkane (HFA) propellant to the vessel; andmixing the propellant with the medicament/surfactant mixture to produce a medicament/surfactant/propellant mixture in which the medicament and the surfactant are suspended in the propellant as a finely divided powder.38. The method of claim 37, further comprising the step of mixing additional HFA propellant with the medicament/surfactant/propellant mixture to produce a further mixture in which the medicament and the surfactant are suspended in propellant as a finely divided powder.39. A method for the treatment of a patient in need of therapy with an inhaled medicament, comprising administering to said patient a therapeutically effective amount of a pharmaceutical aerosol formulation comprising a HFA propellant; a physiologically effective amount of a medicament for inhalation; and an alkyl saccharide surfactant, wherein the medicament and the surfactant are suspended in the propellant as a finely divided powder.40. The method of claim 39, wherein the formulation comprises a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227), and 1,1-difluoroethane (P152a).41. The method of claim 39, wherein the surfactant is selected from the group consisting of an alkyl glucoside and an alkyl maltoside.42. The method of claim 39, wherein the medicament is selected from the group consisting of a β2-adrenoreceptor agonist, an anticholinergic bronchodilator, and a glucocorticosteroid.43. The method of claim 39, wherein the medicament is selected from the group consisting of anti-allergic medicaments, expectorants, mucolytics, antihistamines, cyclooxygenase inhibitors, leukotriene synthesis inhibitors, leukotriene antagonists, phospholipase-A2 (PLA2) inhibitors, platelet aggregating factor (PAF) antagonists, prophylactics of asthma, antiarrhythmic medicaments, tranquilisers, cardiac glycosides, hormones, anti-hypertensive medicaments, antidiabetic medicaments, antiparasitic medicaments, anticancer medicaments, sedatives, analgesic medicaments, antibiotics, antirheumatic medicaments, immunotherapeutic agents, antifungal medicaments, antihypotension medicaments, vaccines, antiviral medicaments, proteins, peptides, vitamins, cell surface receptor blockers, antioxidants, free radical scavengers, and organic salts of N,N′-diacetylcystine.44. The method of claim 39, wherein the ratio of surfactant to medicament is in the range of 1:50 to 1:0.2.45. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of a β2-adrenoreceptor agonist and a glucocorticosteriod.46. The method of claim 45, wherein the formulation further comprises a physiologically effective amount of an anticholinergic bronchodilator.47. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) budesonide, or a salt, ester, solvate, or solvate of a salt or ester thereof.48. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) mometasone, or a salt ester, solvate, or solvate of a salt or ester therefor.49. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) formoterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) fluticasone, or a salt, ester, solvate, or solvate of a salt or ester thereof.50. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) salmeterol, or a salt, ester, solvate, or solvate of a salt or ester thereof; and (b) fluticasone, or a salt, ester, solvate, or solvate of a salt or ester thereof.51. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) formoterol and (b) budesonide.52. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) an anticholinergic bronchodilator and (b) a β2-adrenoreceptor agonist.53. The method of claim 39, wherein the formulation comprises a physiologically effective amount of each of (a) an anticholinergic bronchodilator and (b) a glucocorticosteroid.