Systems and methods for the delivery of corticosteroids having an increased lung deposition

• US 20070197487A1
• Filed: 12/19/2006
• Published: 08/23/2007
• Est. Priority Date: 12/20/2005
• Status: Abandoned Application

• Current Assignee: Tika Lakemedel AB (Astrazeneca PLC)
• Original Assignee: Verus Pharmaceuticals, Inc. (Astrazeneca PLC)
• Inventors: Hill, Malcolm
• Application Number:
  US11/643,730
• Publication Number:
  US 20070197487A1
• Time in Patent Office: Days
• US Class Current: 514/169
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M

Abstract

The present invention relates to methods and systems for the delivery of a corticosteroid comprising (1) an inhalable aqueous mixture comprising a corticosteroid and a solubility enhancer and (2) an inhalable nebulizer, wherein the delivery of the aqueous mixture comprising the corticosteroid by the nebulizer results in an enhanced pharmacokinetic profile of the corticosteroid as compared to conventional inhalable therapies.

Claims

1. An inhalable composition comprising an effective amount of a single corticosteroid, a solvent and a solubility enhancer, wherein upon administration of the composition to a subject through a nebulizer, the composition achieves at least about 35% lung deposition based on the amount of corticosteroid in the composition prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than the corticosteroid.

2. The composition of claim 1, wherein the composition achieves at least about 40% lung deposition based on the amount of corticosteroid in the composition prior to administration.

3. The composition of claim 1, wherein the composition also achieves at least about 85% respirable fraction upon administration.

4. The composition of claim 1, wherein the composition comprises about 60, about 120, about 125, about 240, about 250, about 500, about 1000, about 1500, or about 2000 μ

g of said corticosteroid.

5. The composition of claim 1, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

6. The composition of claim 1, wherein the administration through the nebulizer has a delivery time of less than about 5, less than about 4, less than about 3, less than about 2, or less than about 1.5 minutes.

7. The composition of claim 1, wherein the amount of the single corticosteroid in the composition prior to administration is a nominal dosage of less than about 250 ug.

8. The composition of claim 7, wherein the amount of the single corticosteroid in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

9. The composition of claim 1, wherein the solvent comprises water.

10. The composition of claim 1, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

11. The composition of claim 10, wherein the solubility enhancer comprises SBE7-β

-CD.

12. A method of generating fine particles from an inhalable composition comprising:

adding a solvent and a solubility enhancer to an effective amount of corticosteroid, and

operating a nebulizer to produce fine particles of said composition,

wherein upon administration of the composition to a subject through the nebulizer, the method achieves at least about 35% lung deposition based on the amount of corticosteroid in the composition prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than the corticosteroid.

13. The method of claim 12, wherein the method achieves at least about 40% lung deposition based on the amount of corticosteroid in the composition prior to administration.

14. The method of claim 12, wherein the method also achieves at least about 80% respirable fraction upon administration.

15. The method of claim 12, wherein the method also achieves at least about 85% respirable fraction upon administration.

16. The method of claim 12, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

17. The method of claim 12, wherein the amount of the single corticosteroid in the composition prior to administration is a nominal dosage of less than about 250 ug.

18. The method of claim 17, wherein the amount of the single corticosteroid in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

19. The method of claim 12, wherein the solvent comprises water.

20. The method of claim 12, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

21. The method of claim 20, wherein the solubility enhancer comprises SBE7-β

-CD.

22. An inhalation system for delivering a therapeutically effective dose of a single corticosteroid to a patient comprising:

(a) an aqueous inhalation mixture comprising the corticosteroid and a solubility enhancer, and

(b) a nebulizer

whereby upon administration of the composition to a subject through said nebulizer, the system achieves at least about 35% lung deposition based on the amount of corticosteroid in the mixture prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than the corticosteroid.

23. The system of claim 22, wherein the system achieves at least about 40% lung deposition based on the amount of corticosteroid in the mixture prior to administration.

24. The system of claim 22, wherein the system also achieves at least about 80% respirable fraction upon administration.

25. The system of claim 22, wherein the system also achieves at least about 85% respirable fraction upon administration.

26. The system of claim 22, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

27. The system of claim 22, wherein the amount of the single corticosteroid in the composition prior to administration is a nominal dosage of less than about 250 ug.

28. The system of claim 26, wherein the amount of the single corticosteroid in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

29. The system of claim 22, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

30. The system of claim 29, wherein the solubility enhancer comprises SBE7-β

-CD.

31. A method for the treatment of a bronchoconstrictive disorder in a patient in need of treatment thereof, comprising:

forming a mixture by adding a solvent and a solubility enhancer to an amount of a single corticosteroid and

operating a nebulizer,

wherein upon administration of the mixture to a subject through the nebulizer, the method achieves at least about 35% lung deposition based on the amount of corticosteroid in the mixture prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than the corticosteroid.

32. The method of claim 31, wherein the method achieves at least about 40% lung deposition based on the amount of corticosteroid in the mixture prior to administration.

33. The method of claim 31, wherein the method achieves at least about 45% lung deposition based on the amount of corticosteroid in the mixture prior to administration.

34. The method of claim 31, wherein the method achieves at least about 50% lung deposition based on the amount of corticosteroid in the mixture prior to administration.

35. The method of claim 31, wherein the method achieves between about 40% and about 55% lung deposition based on the amount of corticosteroid in the mixture prior to administration.

36. The method of claim 31, wherein the method also achieves at least about 80% respirable fraction upon administration.

37. The method of claim 31, wherein the method also achieves at least about 85% respirable fraction upon administration.

38. The method of claim 31, wherein the mixture comprises about 60, about 120, about 125, about 240, about 250, about 500, about 1000, about 1500, or about 2000 μ

g of said corticosteroid.

39. The method of claim 31, wherein the amount of the single corticosteroid in the composition prior to administration is a nominal dosage of less than about 250 ug.

40. The method of claim 39, wherein the amount of the single corticosteroid in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

41. The method of claim 31 wherein the solvent comprises water.

42. The method of claim 31 wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-c-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

43. The method of claim 42, wherein the solubility enhancer comprises SBE7-β

-CD.

44. The method of claim 31, wherein said bronchoconstrictive disorder is selected from the group consisting of asthma, pediatric asthma, bronchial asthma, allergic asthma, intrinsic asthma, chronic bronchitis, and emphysema.

45. The method of claim 31, wherein the mixture is administered to a patient not more than once a day.

46. The method of claim 31, wherein the mixture is administered to a patient twice a day or more than twice a day.

47. The method of claim 31, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

48. An inhalable composition comprising an effective amount of budesonide, a solvent and a solubility enhancer, wherein upon administration of the composition to a subject through a nebulizer, the composition achieves at least about 35% lung deposition based on the amount of budesonide in the composition prior to administration wherein the composition is substantially free of active pharmaceutical agents other than the budesonide.

49. The composition of claim 48, wherein the composition achieves at least about 40% lung deposition based on the amount of budesonide in the composition prior to administration.

50. The composition of claim 48, wherein the composition also achieves at least about 85% respirable fraction upon administration.

51. The composition of claim 48, wherein the composition comprises about 60, about 120, about 125, about 240, about 250, about 500, about 1000, about 1500, or about 2000 μ

g of budesonide.

52. The composition of claim 48, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

53. The composition of claim 48, wherein the administration through the nebulizer has a delivery time of less than about 5, less than about 4, less than about 3, less than about 2, or less than about 1.5 minutes.

54. The composition of claim 48, wherein the amount of budesonide in the composition prior to administration is a nominal dosage of less than about 250 ug.

55. The composition of claim 54, wherein the amount of budesonide in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

56. The composition of claim 48, wherein the solvent comprises water.

57. The composition of claim 48, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

58. The composition of claim 57, wherein the solubility enhancer comprises SBE7-β

-CD.

59. An inhalable composition comprising about 60 μ

g budesonide, a solvent and a solubility enhancer, wherein upon administration of the composition to a subject through a nebulizer, the composition achieves lung deposition of at least 20 μ

g of budesonide, wherein the composition is substantially free of active pharmaceutical agents other than the budesonide.

60. An inhalable composition comprising about 120 μ

g budesonide, a solvent and a solubility enhancer, wherein upon administration of the composition to a subject through a nebulizer, the composition achieves lung deposition of at least 40 μ

g of budesonide, wherein the composition is substantially free of active pharmaceutical agents other than the budesonide.

61. An inhalable composition comprising about 240 μ

g budesonide, a solvent and a solubility enhancer, wherein upon administration of the composition to a subject through a nebulizer, the composition achieves lung deposition of at least 80 μ

g of budesonide, wherein the composition is substantially free of active pharmaceutical agents other than the budesonide.

62. A method of generating fine particles from an inhalable composition comprising:

adding a solvent and a solubility enhancer to an effective amount of budesonide, and

operating a nebulizer to produce fine particles of said composition,

wherein upon administration of the composition to a subject through the nebulizer, the method achieves at least about 35% lung deposition based on the amount of budesonide in the composition prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than budesonide.

63. The method of claim 62, wherein the method achieves at least about 40% lung deposition based on the amount of budesonide in the composition prior to administration.

64. The method of claim 62, wherein the method also achieves at least about 80% respirable fraction upon administration.

65. The method of claim 62, wherein the method also achieves at least about 85% respirable fraction upon administration.

66. The method of claim 62, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

67. The method of claim 62, wherein the amount of budesonide in the composition prior to administration is a nominal dosage of less than about 250 ug.

68. The method of claim 67, wherein the amount of budesonide in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

69. The method of claim 62, wherein the solvent comprises water.

70. The method of claim 62, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-β

-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-)-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

71. The method of claim 70, wherein the solubility enhancer comprises SBE7-β

-CD.

72. An inhalation system for delivering a therapeutically effective dose of budesonide to a patient comprising:

(a) an aqueous inhalation comprising budesonide and a solubility enhancer, and

(b) a nebulizer

whereby upon administration of the composition to a subject through said nebulizer, the system achieves at least about 35% lung deposition based on the amount of budesonide in the mixture prior to administration, and wherein the mixture is substantially free of active pharmaceutical agents other than budesonide.

73. The system of claim 72, wherein the system achieves at least about 40% lung deposition based on the amount of budesonide in the mixture prior to administration.

74. The system of claim 72, wherein the system also achieves at least about 80% respirable fraction upon administration.

75. The system of claim 72, wherein the system also achieves at least about 85% respirable fraction upon administration.

76. The system of claim 72, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

77. The system of claim 72, wherein the amount of budesonide in the composition prior to administration is a nominal dosage of less than about 250 ug.

78. The system of claim 77, wherein the amount of budesonide in the composition prior to administration is about 120 ug, about 60 ug or about 40 ug.

79. The system of claim 72, wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-α

-CD, SBE-β

-CD, SBE1-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

80. The system of claim 79, wherein the solubility enhancer comprises SBE7-β

-CD.

81. A method for the treatment of a bronchoconstrictive disorder in a patient in need of treatment thereof, comprising:

forming a mixture by adding a solvent and a solubility enhancer to an amount of budesonide and

operating a nebulizer,

wherein upon administration of the mixture to a subject through the nebulizer, the method achieves at least about 35% lung deposition based on the amount of budesonide in the mixture prior to administration, and wherein the composition is substantially free of active pharmaceutical agents other than budesonide.

82. The method of claim 81, wherein the method achieves at least about 40% lung deposition based on the amount of budesonide in the mixture prior to administration.

83. The method of claim 81, wherein the method achieves at least about 45% lung deposition based on the amount of budesonide in the mixture prior to administration.

84. The method of claim 81, wherein the method achieves at least about 50% lung deposition based on the amount of budesonide in the mixture prior to administration.

85. The method of claim 81, wherein the method achieves between about 40% and about 55% lung deposition based on the amount of budesonide in the mixture prior to administration.

86. The method of claim 81, wherein the method also achieves at least about 80% respirable fraction upon administration.

87. The method of claim 81, wherein the method also achieves at least about 85% respirable fraction upon administration.

88. The method of claim 81, wherein the mixture comprises about 60, about 120, about 125, about 240, about 250, about 500, about 1000, about 1500, or about 2000 μ

g of budesonide.

89. The method of claim 81, wherein the amount of budesonide in the composition prior to administration is a nominal dosage of less than about 250 ug.

90. The method of claim 81 wherein the solvent comprises water.

91. The method of claim 81 wherein the solubility enhancer is selected from the group consisting of propylene glycol, non-ionic surfactants, tyloxapol, polysorbate 80, vitamin E-TPGS, macrogol-15-hydroxystearate, phospholipids, lecithin, purified and/or enriched lecithin, phosphatidylcholine fractions extracted from lecithin, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), cyclodextrins and derivatives thereof, SAE-CD derivatives, SBE-c-CD, SBE-β

-CD, SBE1-CD, SBE4-β

-CD, SBE7-β

-CD, SBE-γ

-CD, dimethyl β

-CD, hydroxypropyl-β

-cyclodextrin, 2-HP-β

-CD, hydroxyethyl-β

-cyclodextrin, hydroxypropyl-γ

-cyclodextrin, hydroxyethyl-γ

-cyclodextrin, dihydroxypropyl-β

-cyclodextrin, glucosyl-α

-cyclodextrin, glucosyl-β

-cyclodextrin, diglucosyl-β

-cyclodextrin, maltosyl-α

-cyclodextrin, maltosyl-β

-cyclodextrin, maltosyl-γ

-cyclodextrin, maltotriosyl-β

-cyclodextrin, maltotriosyl-γ

-cyclodextrin, dimaltosyl-β

-cyclodextrin, methyl-β

-cyclodextrin, carboxyalkyl thioether derivatives, ORG 26054, ORG 25969, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of vinyl acetate, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and combinations thereof.

92. The method of claim 91, wherein the solubility enhancer comprises SBE7-β

-CD.

93. The method of claim 81, wherein said bronchoconstrictive disorder is selected from the group consisting of asthma, pediatric asthma, bronchial asthma, allergic asthma, intrinsic asthma, chronic bronchitis, and emphysema.

94. The method of claim 81, wherein the mixture is administered to a patient not more than once a day.

95. The method of claim 81, wherein the mixture is administered to a patient twice a day or more than twice a day.

96. The method of claim 87, wherein the nebulizer is selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.

97. The method of claim 81, wherein the mixture comprises about 60 μ

g of budesonide, wherein upon administration of the mixture to a subject through a nebulizer, the composition achieves lung deposition of at least 20 μ

g of budesonide.

98. The method of claim 81, wherein the mixture comprises 120 μ

g of budesonide, wherein upon administration of the mixture to a subject through a nebulizer, the composition achieves lung deposition of at least 40 μ

g of budesonide.

99. The method of claim 81, wherein the mixture comprises 240 μ

g of budesonide, wherein upon administration of the mixture to a subject through a nebulizer, the composition achieves lung deposition of at least 80 μ

g of budesonide.