Compositions comprising azelastine and methods of use thereof

• US 20060110331A1
• Filed: 11/22/2005
• Published: 05/25/2006
• Est. Priority Date: 11/24/2004
• Status: Active Grant

• Current Assignee: Meda Pharmaceuticals Incorporated (Mylan N.V.)
• Original Assignee: Medpointe Healthcare Incorporated (Mylan N.V.)
• Inventors: Balwani, Gul, D'Addio, Alexander D., Lawrence, Brian D., Dang, Phuong Grace
• Granted Patent: US 8,071,073 B2
• Time in Patent Office: Days
• 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 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• 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
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention provides pharmaceutical compositions comprising azelastine, or a pharmaceutically acceptable salt or ester thereof including azelastine hydrochloride, and optionally one or more additional active agents. Preferred such compositions further comprise one or more pharmaceutically acceptable carriers or excipients that reduce the amount of post-nasal drip, and/or that minimize or mask the unpleasant bitter taste associated with post-nasal drip, of the compositions into the oral cavity, upon intranasal or ocular administration of the compositions. Especially effective excipients used in the compositions of the present invention are hypromellose as a viscosity modifier and sucralose as a taste-masking agent. The invention also provides methods of treating or preventing certain disorders, or symptomatic relief therefrom, by administering the compositions of the invention to a patient, e.g., for the symptomatic relief of allergic rhinitis, non-allergic vasomotor rhinitis, allergic conjunctivitis, as well as other disorders. The compositions and methods of the present invention provide significant value in terms of patient acceptability, convenience, and compliance.

Claims

1. A pharmaceutical composition comprising azelastine, or a pharmaceutically acceptable salt or ester thereof, at a concentration of about 0.005% to about 5.0% by weight, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of said pharmaceutically acceptable carriers or excipients is a taste-masking agent that masks the taste of said azelastine or salt or ester thereof such that the sensation of a bitter taste by a patient caused by administration of said pharmaceutical composition to said patient is reduced or eliminated.

2. The pharmaceutical composition of claim 1, wherein said composition comprises azelastine hydrochloride.

3. The pharmaceutical composition of claim 1, wherein said taste-masking agent is selected from the group consisting of sucralose, sucrose, saccharin or a salt thereof, fructose, dextrose, corn syrup, aspartame, acesulfame-K, xylitol, sorbitol, erythritol, ammonium glycyrrhizinate, thaumatin, neotame, mannitol, menthol, eucalyptus oil, camphor, a natural flavoring agent, an artificial flavoring agent, and combinations thereof.

4. The pharmaceutical composition of claim 3, wherein said taste-masking agent is sucralose.

5. The pharmaceutical composition of claim 4, wherein sucralose is present in said composition at a concentration of from about 0.001% to about 1% (w/v).

6. The pharmaceutical compositions of claim 5, wherein said sucralose is present in said composition at a concentration of from about 0.01% to about 0.5%.

7. The pharmaceutical composition of claim 6, wherein said sucralose is present in said composition at a concentration of from about 0.02% to about 0.2%.

8. The pharmaceutical composition of claim 7, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15%.

9. The pharmaceutical composition of claim 4, further comprising one or more additional taste-masking agents.

10. The pharmaceutical composition of claim 9, wherein said additional taste-masking agent is menthol.

11. The pharmaceutical composition of claim 1, wherein said composition is formulated for intranasal administration.

12. The pharmaceutical composition of claim 1, wherein said composition is formulated for ocular administration.

13. The pharmaceutical composition of claim 11, wherein said composition comprises at least one viscosity-increasing agent that reduces or prevents postnasal drip of said composition into the pharynx upon intranasal administration of said composition.

14. The pharmaceutical composition of claim 13, wherein said viscosity-increasing agent is selected from the group consisting of a polyvinylpyrrolidone, a cellulose derivative, carrageenan, guar gum, an alginate, a carbomer, a polyethylene glycol, a polyvinyl alcohol and xanthan gum.

15. The pharmaceutical composition of claim 14, wherein said cellulose derivative is selected from the group consisting of hydroxyethyl cellulose, carboxymethyl cellulose and hypromellose.

16. The pharmaceutical composition of claim 15, wherein said viscosity-increasing agent is hypromellose.

17. The pharmaceutical composition of claim 16, wherein said hypromellose is hypromellose 2900 USP 4000 at a concentration of about 0.05% to about 0.5% (w/v).

18. The pharmaceutical composition of claim 12, wherein said composition comprises at least one viscosity-increasing agent that reduces or prevents postnasal drip of said composition into the pharynx upon intranasal administration of said composition.

19. The pharmaceutical composition of claim 18, wherein said viscosity-increasing agent is selected from the group consisting of a polyvinylpyrrolidone, a cellulose derivative, carrageenan, guar gum, an alginate, a carbomer, a polyethylene glycol, a polyvinyl alcohol and xanthan gum.

20. The pharmaceutical composition of claim 19, wherein said cellulose derivative is selected from the group consisting of hydroxyethyl cellulose, carboxymethyl cellulose and hypromellose.

21. The pharmaceutical composition of claim 20, wherein said viscosity-increasing agent is hypromellose.

22. The pharmaceutical composition of claim 21, wherein said hypromellose is hypromellose 2900 USP 4000 at a concentration of about 0.05% to about 0.5% (w/v).

23. The pharmaceutical composition of claim 1, further comprising one or more additional components selected from the group consisting of one or more solvents, one or more preservatives, one or more stabilizers, one or more solubility-improving agents, one or more isotonicity agents, and one or more buffers.

33. A method of treating or preventing a physical disorder in an animal suffering from or predisposed thereto, comprising administering to said animal an effective amount of the pharmaceutical composition of any one of claims 1, 4, 9, 12, 18 and 24.

34. The method of claim 33, wherein said animal is a mammal.

35. The method of claim 34, wherein said mammal is a human.

36. The method of claim 33, wherein said physical disorder is selected from the group consisting of allergic rhinitis, non-allergic vasomotor rhinitis and allergic conjunctivitis.

24. A pharmaceutical composition comprising:

about 0.005% to about 0.5% (w/v) azelastine hydrochloride;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.001% to about 1.0% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

25. The pharmaceutical composition of claim 24, wherein said composition comprises azelastine hydrochloride at a concentration of from about 0.05% to about 0.15% (w/v).

26. The pharmaceutical composition of claim 24, wherein said water soluble polymer is hypromellose.

27. The pharmaceutical composition of claim 26, wherein said hypromellose is present in said composition at a concentration sufficient to provide a viscosity of said solution of from about 2 centipoise to about 300 centipoise.

28. The pharmaceutical composition of claim 27, wherein said hypromellose is present in said composition at a concentration of from about 0.1% to about 0.3% (w/v).

29. The pharmaceutical composition of claim 24, wherein said composition comprises sucralose at a concentration of from about 0.05% to about 0.15% (w/v).

30. The pharmaceutical composition of claim 24, further comprising menthol at a concentration of from about 0.01% to about 1% (w/v).

31. The pharmaceutical composition of claim 30, wherein said menthol is present in said composition at a concentration of from about 0.05% to about 0.1%.

32. The pharmaceutical composition of claim 24, wherein the osmolality of said composition is from about 250 mosmol/kg to about 320 mosmol/kg.

37. An oral dosage pharmaceutical composition comprising a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, at a concentration of from about 0.05% to about 5.0% by weight, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of said pharmaceutically acceptable carriers or excipients is sucralose.

38. The oral dosage pharmaceutical composition of claim 37, wherein said azelastine is present in said composition at a concentration of about 0.125% to about 0.15%.

39. The oral dosage pharmaceutical composition of claim 37, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

40. The oral dosage pharmaceutical composition of claim 37, wherein said azelastine is present in said composition at a concentration of about 0.1% by weight and said sucralbse is present in said composition at a concentration of about 0.15% by weight.

41. The oral dosage pharmaceutical composition of claim 37, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight and said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

42. The oral dosage pharmaceutical composition of claim 37, wherein said azelastine is present in said composition at a concentration of about 0.15% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

43. The oral dosage pharmaceutical composition of claim 37, wherein said composition is in the form of a liquid solution or suspension.

44. The oral dosage pharmaceutical composition of claim 37, wherein said composition is in the form of a tablet or capsule.

45. The oral dosage pharmaceutical composition of claim 37, wherein said composition is a chewable tablet.

46. The oral dosage pharmaceutical composition of claim 37, wherein said composition is an orally disintegrating tablet.

47. The oral dosage pharmaceutical composition of claim 37, wherein said composition is an effervescent composition.

48. The oral dosage pharmaceutical composition of claim 37, wherein said composition is an orally dissolving/consumable film.

49. A pharmaceutical composition comprising a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, at a concentration of from about 0.05% to about 5% by weight, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of said pharmaceutically acceptable carriers or excipients is sucralose, and wherein said pharmaceutical composition further comprises one or more additional active agents.

50. The pharmaceutical composition of claim 49, wherein said one or more additional active agents are selected from the group consisting of:

(a) one or more antihistamines;

(b) one or more steroids;

(c) one or more leukotriene antagonists;

(d) one or more decongestants; and

(e) one or more non-steroidal anti-inflammatory agents.

51. The pharmaceutical composition of claim 50, wherein said one or more antihistamines are selected from the group consisting of cetirizine, olopatadine, fexofenadine, terfenadine and loratadine.

52. The pharmaceutical composition of claim 50, wherein said one or more steroids are selected from the group consisting of fluoromethalone, fluticasone, mometasone, triamcinolone, betamethasone, flunisolide, budesonide, beclomethasone, budesonide, rimexolone, loteprednol, beloxil, prednisone, loteprednol and dexamethasone.

53. The pharmaceutical composition of claim 50, wherein said one or more leukotriene antagonists are selected from the group consisting of montelukast, zafirlukast and zanamivir

54. The pharmaceutical composition of claim 50, wherein said one or more decongestants are selected from the group consisting of pseudoephedrine, phenylephedrine, phenylephrine, phenylpropanolamine, oxymetazoline, propylhexedrine, xylometazoline, epinephrine, ephedrine, desoxyephedrine, naphazoline, naphazoline, and tetrahydrozoline.

55. The pharmaceutical composition of claim 50, wherein said non-steroidal anti-inflammatory agents are selected from the group consisting of ibuprofen, diclofenac, naproxen, etodolac, flurbiprofen, fenoprofen, ketoprofen, suprofen, fenbufen, fluprofen, tolmetin sodium, oxaprozin, zomepirac, sulindac indomethacin, piroxicam, mefenamic acid, nabumetone, meclofenamate sodium, diflunisal, flufenisal, piroxicam, ketorolac, sudoxicam and isoxicam.

56. The pharmaceutical composition of claim 50, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight.

57. The pharmaceutical composition of claim 50, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

58. The pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof, sucralose and one or more steroids.

59. The pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof, sucralose and one or more decongestants.

60. The pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof, sucralose, one or more steroids and one or more decongestants.

61. The oral dosage pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof at a concentration of about 0.05% to about 0.15% by weight, sucralose at a concentration of about 0.05% to about 0.15% by weight, and one or more steroids at a concentration of about 0.01% to about 0.1%.

62. The pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof at a concentration of about 0.05% to about 0.15% by weight, sucralose at a concentration of about 0.05% to about 0.15% by weight, and one or more decongestants at a concentration of about 0.1% to about 1.0%.

63. The pharmaceutical composition of claim 50, wherein said composition comprises azelastine, or a pharmaceutically acceptable salt or ester thereof at a concentration of about 0.05% to about 0.15% by weight, sucralose at a concentration of about 0.05% to about 0.15% by weight, one or more steroids at a concentration of about 0.01% to about 0.1%, and one or more decongestants at a concentration of about 0.1% to about 1.0%.

64. The pharmaceutical composition of claim 50, wherein said composition is formulated for intranasal administration.

65. The pharmaceutical composition of claim 50, wherein said composition is formulated for ocular administration.

66. A sustained release pharmaceutical composition, comprising a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of said pharmaceutically acceptable carriers or excipients is sucralose, and wherein said azelastine, or said pharmaceutically acceptable salt or ester thereof, is:

(a) coated with one or more sustained release components;

(b) bound to a cation exchanger;

(c) reacted with one or more osmotically active substances and coated with a semi-permeable membrane and a hole is bored into the membrane;

or

(d) embedded in, or is bound to, one or more substances selected from of the group consisting of digestible fats, indigestible fats, polymers and swelling agents.

67. The sustained release pharmaceutical composition of claim 66, wherein said azelastine is present in said composition at a concentration of from about 0.5% to about 5.0% by weight.

68. The sustained release pharmaceutical composition of claim 66, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

69. The sustained release pharmaceutical composition of claim 66, wherein said azelastine is present in said composition at a concentration of about 0.1% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

70. The sustained release pharmaceutical composition of claim 66, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight and said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

71. The sustained release pharmaceutical composition of claim 66, wherein said azelastine is present in said composition at a concentration of about 0.15% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

72. A liquid, unit-dose pharmaceutical composition, comprising a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of said pharmaceutically acceptable carriers or excipients is sucralose, wherein said composition is free, or substantially free of preservatives, and wherein said composition is provided in a single unit-dose container.

73. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said azelastine is present in said composition at a concentration of from about 0.05% to about 5.0% by weight.

74. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

75. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said azelastine is present in said composition at a concentration of about 0.1% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

76. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight and said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

77. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said azelastine is present in said composition at a concentration of about 0.15% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

78. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said single unit-dose container comprises high density polyethylene.

79. The liquid, unit-dose pharmaceutical composition of claim 72, wherein said single unit-dose container is a blow-fill-seal high density polyethylene container with a volume capacity of about 1.0 mL.

80. An inhalable powder pharmaceutical composition comprising, a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers or excipients, wherein said azelastine is in the form of micronized particles and wherein at least one of said pharmaceutically acceptable carriers or excipients is micronized particles of sucralose.

81. The inhalable powder pharmaceutical composition of claim 80, wherein said micronized particles of azelastine have an average particle size of about 1 μ

m to about 5 μ

m.

82. The inhalable powder pharmaceutical composition of claim 80, wherein said micronized particles of sucralose have an average particle size of about 15 μ

m to about 80 μ

m.

83. The inhalable powder pharmaceutical composition of claim 80, wherein said composition is formulated for delivery using a dry powder inhaler.

84. The inhalable powder pharmaceutical composition of claim 80, wherein said azelastine is present in said composition at a concentration of from about 0.1% to about 0.15% by weight.

85. The inhalable powder pharmaceutical composition of claim 80, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

86. The inhalable powder pharmaceutical composition of claim 80, wherein said azelastine is present in said composition at a concentration of about 0.1% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

87. The inhalable powder pharmaceutical composition of claim 80, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight and said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

88. The inhalable powder pharmaceutical composition of claim 80, wherein said azelastine is present in said composition at a concentration of about 0.15% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

89. A method of treating snoring in an animal, comprising administering to the animal a therapeutically effective dose of azelastine, or a pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers or excipients, wherein at least one of the pharmaceutically acceptable carriers or excipients is sucralose.

90. The method of claim 89, wherein said azelastine is present in said composition at a concentration of from about 0.1% to about 0.15% by weight.

91. The method of claim 89, wherein said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

92. The method of claim 89, wherein said azelastine is present in said composition at a concentration of about 0.1% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

93. The method of claim 89, wherein said azelastine is present in said composition at a concentration of from about 0.125% to about 0.15% by weight and said sucralose is present in said composition at a concentration of from about 0.05% to about 0.15% by weight.

94. The method of claim 89, wherein said azelastine is present in said composition at a concentration of about 0.15% by weight and said sucralose is present in said composition at a concentration of about 0.15% by weight.

95. The method of claim 89, wherein said composition is administered in a nasal spray.

96. The method of claim 89, wherein said animal is a human.

97. A method of treating or preventing allergic rhinitis, non-allergic vasomotor rhinitis or allergic conjunctivitis in an animal suffering from or predisposed thereto, comprising administering to said animal a pharmaceutical composition comprising an effective amount azelastine and taste-masking amount of sucralose, thereby avoiding the bitter taste associated with the azelastine.

98. The method of claim 97, wherein said animal is a mammal.

99. The method of claim 98, wherein said mammal is a human.

100. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride; and

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone.

136. A method of treating or preventing a physical disorder in an animal suffering from or predisposed thereto, comprising administering to said animal an effective amount of the pharmaceutical composition of any one of claims 100-135.

137. The method of claim 136, wherein said animal is a mammal.

138. The method of claim 137, wherein said mammal is a human.

139. The method of claim 136, wherein said physical disorder is selected from the group consisting of allergic rhinitis, non-allergic vasomotor rhinitis and allergic conjunctivitis.

101. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone; and

about 0.1% to about 0.15% (w/v) sucralose.

102. Apharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone; and

about 0.1% (w/v) sucralose.

103. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone; and

about 0.15% (w/v) sucralose.

104. A pharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone; and

about 0.15% (w/v) sucralose.

105. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride; and

about 0.1% to about 5.0% (w/v) montelukast.

106. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.1% to about 0.15% (w/v) sucralose.

107. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.1% (w/v) sucralose.

108. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.15% (w/v) sucralose.

109. A pharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.15% (w/v) sucralose.

110. Apharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride; and

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine.

111. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.1% to about 0.15% (w/v) sucralose.

112. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.1% (w/v) sucralose.

113. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.15% (w/v) sucralose.

114. Apharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.15% (w/v) sucralose.

115. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride; and

about 0.1% to about 10.0% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen.

116. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 10.0% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen; and

about 0.1% to about 0.15% (w/v) sucralose.

117. A pharmaceutical composition comprising:

about 0.05% (w/v) azelastine hydrochloride;

about 0.1% to about 10.0% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen; and

about 0.1% (w/v) sucralose.

118. A pharmaceutical composition comprising:

about 0.05% (w/v) azelastine hydrochloride;

about 0.1% to about 10.0% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen; and

about 0.15% (w/v) sucralose.

119. A pharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 10.0% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen; and

about 0.15% (w/v) sucralose.

120. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone; and

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine.

121. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.1% to about 0.15% (w/v) sucralose.

122. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.1% (w/v) sucralose.

123. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.15% (w/v) sucralose.

124. A pharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 1.0% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine; and

about 0.15% (w/v) sucralose.

125. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone; and

about 0.1% to about 5.0% (w/v) montelukast.

126. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.1% to about 0.15% (w/v) sucralose.

127. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.1% (w/v) sucralose.

128. A pharmaceutical composition comprising:

about 0.1% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.15% (w/v) sucralose.

129. A pharmaceutical composition comprising:

about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triamcinolone;

about 0.1% to about 5.0% (w/v) montelukast; and

about 0.15% (w/v) sucralose.

130. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, and triaamcinolone;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

131. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 5% (w/v) montelukast;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

132. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 1% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

133. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 10% (w/v) NSAID selected from the group consisting of ibuprofen, diclofenac, aceclofenac and naproxen;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

134. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone;

about 0.1% to about 1% (w/v) decongestant selected from the group consisting of pseudoephedrine and phenylephrine;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.

135. A pharmaceutical composition comprising:

about 0.05% to about 0.15% (w/v) azelastine hydrochloride;

about 0.01% to about 0.1% (w/v) steroid selected from the group consisting of fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide and triamcinolone;

about 0.1% to about 5% (w/v) montelukast;

about 0.001% to about 5.00% (w/v) of a water-soluble polymer;

about 0.01% to about 0.1% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride;

about 0.1% to about 0.15% sucralose;

a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within a range of from about 4.5 to about 7.4;

a sufficient amount of an isotonicity agent to yield an osmolality of about 220 mosmol/kg to about 350 msomol/kg; and

QS water.