Compositions Comprising Azelastine and Methods of Use Thereof

• US 20100152147A1
• Filed: 09/29/2009
• Published: 06/17/2010
• Est. Priority Date: 11/24/2004
• Status: Active Grant

• Current Assignee: Meda Pharmaceuticals Incorporated (Mylan N.V.)
• Original Assignee: Meda Pharmaceuticals Incorporated (Mylan N.V.)
• Inventors: Higson, John, Balwani, Gul, Fuge, Dennis, D'Addio, Alexander D., Roecklein, Bryan A.
• Granted Patent: US 8,758,816 B2
• Time in Patent Office: Days
• US Class Current: 514/179
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

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 generally relates to pharmaceutical compositions comprising one or more active pharmaceutical ingredients, such as azelastine or pharmaceutically acceptable salts or esters thereof including azelastine hydrochloride, particularly wherein the compositions are provided in unit dosage form. In certain embodiments, the invention provides such unit dosage pharmaceutical compositions comprising azelastine hydrochloride formulated for use as nasal sprays and/or ocular solutions or drops. 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 a variety of allergic and non-allergic conditions, particularly conjunctivitis, sinusitis, rhinitis and rhinosinusitis. The compositions and methods of the present invention provide significant value in terms of patient acceptability, convenience, and compliance.

Claims

1. A composition of matter comprising:

(a) a single unit dosage of a pharmaceutical composition; and

(b) a unit dosage container comprising;

(i) a squeezable chamber holding said single unit dosage and having an opening wherein said single unit dosage exits said opening when said squeezable chamber is squeezed; and

(ii) a closure mechanism removably attached to said opening of said squeezable chamber,

wherein said unit dosage container is made of high density polyethylene (HDPE) and wherein said single unit dosage of said pharmaceutical composition has a volume of less than about 0.6 ml, and wherein said squeezable chamber has a volume of less than or equal to about 1.0 ml.

2. The composition of matter of claim 1, wherein said volume of said single unit dosage of the pharmaceutical composition is in a range of from about 0.1 ml to about 0.5 ml.

3. The composition of matter of claim 1, wherein said squeezable chamber has a volume of about 0.5 ml to about 1.0 ml.

4. The composition of matter of claim 1, further comprising:

an extension attached to said squeezable chamber having opposed first and second surfaces, wherein identification can be located on at least one of said first and second surfaces.

5. The composition of matter of claim 4, wherein said identification is engraved on said extension.

6. The composition of matter of claim 4, wherein said identification indicates the contents of the unit dosage container.

7. The composition of matter of claim 4, wherein said identification is in writing.

8. The composition of matter of claim 4, wherein said identification indicates an expiration date of said pharmaceutical composition.

9. The composition of matter of claim 1, wherein said pharmaceutical composition comprises an active pharmaceutical ingredient selected from the group consisting of one or more antihistamines, one or more steroids, one or more leukotriene antagonists, one or more prostaglandin D2 receptor antagonists, one or more decongestants, one or more expectorants, one or more anti-fungal agents, triamcinolone or one or more triamcinolone derivatives, one or more non-steroidal immunophilin-dependent immunosuppressants (NsIDIs), one or more anti-inflammatory agents, one or more non-steroidal anti-inflammatory agents (NSAIDs), one or more COX-2 inhibitors, one or more anti-infective agents, one or more mucolytic agents, one or more anticholinergic agents, one or more mast cell stabilizers, one or more non-antibiotic anti-microbial agents, one or more anti-viral agents, one or more antiseptics, one or more neurokinin antagonists, platelet activating factor (PAF) and one or more 5-lipoxygenase (5-LO) inhibitors.

10. The composition of matter of claim 9, wherein said pharmaceutical composition comprises one or more antihistamines.

11. The composition of matter of claim 10, wherein said one or more antihistamines are selected from the group consisting of azelastine, acrivastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, doxylamine, dimethindene, ebastine, epinastine, efletirizine, ketotifen, levocabastine, mizolastine, mequitazine, mianserin, noberastine, meclizine, norastemizole, olopatadine, picumast, tripelenamine, temelastine, trimeprazine, triprolidine, bromopheniramine, chlorpheniramine, dexchlorpheniramine, triprolidine, clemastine, diphenhydramine, diphenylpyraline, tripelennamine, hydroxyzine, methdilazine, promethazine, trimeprazine, azatadine, cyproheptadine, antazoline, pheniramine, pyrilamine, astemizole, terfenadine, loratadine, cetirizine, levocetirizine, fexofenadine, descarboethoxyloratadine, desloratadine, dimenhydrinate and hydroxyzine, and pharmaceutically acceptable salts, esters and derivatives thereof.

12. The composition of matter of claim 10, wherein said pharmaceutical composition comprises azelastine or a pharmaceutically acceptable salt thereof.

13. The composition of matter of claim 12, wherein said pharmaceutical composition comprises azelastine hydrochloride.

14. The composition of matter of claim 9, wherein said one or more steroids are selected from the group consisting of fluoromethalone, fluticasone, mometasone, triamcinolone, betamethasone, flunisolide, budesonide, beclomethasone, rimexolone, loteprednol, beloxil, prednisone and dexamethasone, and pharmaceutically acceptable conjugates, salts, esters, variants or derivatives thereof.

15. The composition of matter of claim 14, wherein said steroid is fluticasone or a pharmaceutically acceptable conjugate, salt, ester, variant or derivative thereof.

16. The composition of matter of claim 15, wherein said steroid is selected from the group consisting of fluticasone propionate fluticasone dipropionate, fluticasone fuorate, fluticasone maleate and fluticasone valerate.

17. The composition of matter of claim 9, wherein said one or more leukotriene antagonists are selected from the group consisting of albuterol sulfate, aminophylline, amoxicillin, ampicillin, astemizole, attenuated tubercle bacillus, azithromycin, bacampicillin, beclomethasone dipropionate, budesonide, bupropion hydrochloride, cefaclor, cefadroxil, cefixime, cefprozil, cefuroxime axetil, cephalexin, ciprofloxacin hydrochloride, clarithromycin, clindamycin, cloxacillin, doxycycline, erythromycin, ethambutol, fenoterol hydrobromide, fluconazole, flunisolide, fluticasone propionate, formoterol fumarate, gatifloxacin, influenza virus vaccine, ipratropium bromide, isoniazid, isoproterenol hydrochloride, itraconazole, ketoconazole, ketotifen, levofloxacin, minocycline, montelukast, moxifloxacin, nedocromil sodium, nicotine, nystatin, ofloxacin, orciprenaline, oseltamivir, oseltamivir sulfate, oxtriphylline, penicillin, pirbuterol acetate, pivampicillin, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, prednisone, pyrazinamide, rifampin, salbutamol, salmeterol xinafoate, sodium cromoglycate, terbutaline sulfate, terfenadine, theophylline, triamcinolone acetonide, zafirlukast and zanamivir.

18. The composition of matter of claim 9, wherein said pharmaceutical composition comprises one or more prostaglandin D2 receptor antagonists.

19. The composition of matter of claim 9, wherein said one or more decongestants are selected from the group consisting of pseudoephedrine, phenylephedrine, phenylephrine, phenylpropanolamine, oxymetazoline, propylhexedrine, xylometazoline, epinephrine, ephedrine, desoxyephedrine, naphazoline, and tetrahydrozoline.

20. The composition of matter of claim 9, wherein said one or more expectorants are selected from the group consisting of guaifenesin, sodium cromoglycate, codeine phosphate and isoproternol hydrochloride.

21. The composition of matter of claim 9, wherein said one or more anti-fungal agents are selected from the group consisting of amphotericin B, nystatin, fluconazole, ketoconazole, terbinafine, itraconazole, imidazole, triazole, ciclopirox, clotrimazole, and miconazole.

22. The composition of matter of claim 9, wherein said pharmaceutical composition comprises a triamcinolone or one or more triamcinolone derivatives.

23. The composition of matter of claim 9, wherein said one or more non-steroidal anti-inflammatory agents are selected from the group consisting of ibuprofen, diclofenac, aceclofenac, 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.

24. The composition of matter of claim 9, wherein said one or more non-steroidal immunophilin-dependent immunosuppressants (NsIDIs) are selected from the group consisting of cyclosporine, tacrolimus, ascomycin, pimecrolimus, rapamycin, everolimus, and other agents that inhibit calcineurin.

25. The composition of matter of claim 9, wherein said one or more COX-2 inhibitors are selected from the group consisting of rofecoxib, celecoxib, valdecoxib, lumiracoxib, meloxicam, and nimesulide.

26. The composition of matter of claim 9, wherein said one or more anti-infective agents are selected from the group consisting of penicillin, beta lactam antibiotics, cephalosporins, macrolides, ketolides, sulfonamides, quinolones, aminoglycosides, cefuroxime, vancomycin, amoxicillin, gentamicin and linezolid

27. The composition of matter of claim 9, wherein said one or more mucolytic agents are selected from the group consisting of acetylcysteine and dornase alpha.

28. The composition of matter of claim 9, wherein said pharmaceutical composition comprises one or more anticholinergic agents selected from the group consisting of mivacurium, atracurium, fazadinium, rocuronium, vecuronium, doxacurium, metocurine, pancuronium, pipecuronium, gallamine, hexafluoronium, suxamethonium, succinylcholine, decamethonium, atropine, scopolamine, hyoscyamine, benzatropine, trihexyphenidyl, biperiden, glycopyrrolate, ipratropium, pirenzepine, telenzepine, tiotropium, darifenacin, vedaclidine, tropicamide, cyclopentolate, dicycloverine, tolterodine, oxybutynin, homatropine, orphenadrine, diphenhydramine, hemicholinium-3, vesamicol, pralidoxime, obidoxime, oxitropium, alcuronium, dimethyltubocurarine, tubocurarine and ipratropium.

29. The composition of matter of claim 9, wherein said one or more mast cell stabilizers are selected from the group consisting of cromolyn and nedcromil sodium.

30. The composition of matter of claim 9, wherein said one or more non-antibiotic anti-microbial agents is taurolidine.

31. The composition of matter of claim 9, wherein said pharmaceutical composition comprises one or more anti-viral agents are selected from the group consisting of abacavir, acyclovir, adefovir, amantadine, amprenavir, arbidol, atazanavir, atripla boceprevir, cidofovir, combivir, darunavir delavirdine, didanosine, docosanol, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fomivirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, ibacitabine, immunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitor, lamivudine, lopinavir, loviride, maraviroc, moroxydine, nelfinavir, nevirapine nexavir, oseltamivir, peginterferon alfa-2a, penciclovir, peramivir, pleconaril, podophyllotoxin, raltegravir, ribavirin, rimantadine, ritonavir, saquinavir, stavudine, tenofovir, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir and zidovudine.

32. The composition of matter of claim 9, wherein said one or more antiseptics are selected from the group consisting of iodine, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide.

33. The composition of matter of claim 9, wherein said one or more neurokinin antagonists are selected from the group consisting of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazolines, quinolines, isoquinolines, azanorbornanes, naphthyridines and benzodiazepines.

34. The composition of matter of claim 9, wherein said one or more 5-lipoxygenase inhibitors are selected from the group consisting of zileuton, docebenone, piripost and tenidap.

35. The composition of matter of claim 9, wherein said pharmaceutical composition further comprises one or more additional active pharmaceutical ingredients.

36. The composition of matter of claim 35, wherein said one or more additional active pharmaceutical ingredients is 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.

37. A composition of matter comprising:

(a) a plurality of unit dosage containers, each of said unit dosage containers comprising a single unit dosage of a pharmaceutical composition, wherein each unit dosage container comprises;

(b) a squeezable chamber holding said single unit dosage and having an opening wherein said single unit dosage exits said opening when said squeezable chamber is squeezed; and

(c) a closure mechanism removably attached to said opening of said squeezable chamber,

wherein said unit dose container is made of high density polyethylene (HDPE) and wherein said single unit dosage of said pharmaceutical composition has a volume of less than about 0.6 ml and wherein said squeezable chamber has a volume of less than or equal to about 1.0 ml.

38. The composition of matter of claim 37, wherein said volume of said single unit dosage of said pharmaceutical composition is in a range from about 0.1 ml to about 0.5 ml.

39. The composition of matter of claim 37, wherein said squeezable chamber has a volume of about 0.5 ml to about 1.0 ml.

40. An assembly comprising the composition of matter of claim 37, wherein at least two of said unit dosage containers are removably attached to each other.

41. A container comprising the composition of matter of claim 37.

42. The container of claim 40, further comprising instructions for use of the unit dosage containers.

43. A unit dosage form comprising a unit dosage container made of high density polyethylene, said unit dosage form having a volume of less than about 0.6 ml and said dosage container having a volume of less than about 1.0 ml, said unit dosage form containing one or more antihistamines or pharmaceutically acceptable salts thereof.

44. The unit dosage form of claim 43, wherein said antihistamine comprises azelastine or a pharmaceutically acceptable salt thereof.

45. The unit dosage form of claim 44, wherein said unit dosage form comprises azelastine hydrochloride.

46. The unit dosage form of claim 43, further comprising one more pharmaceutically acceptable carriers or diluents.

47. The unit dosage form of claim 43, further comprising one or more additional active pharmaceutical ingredients.

48. The unit dosage form of claim 47, wherein said one or more additional active pharmaceutical ingredients is selected from the group consisting of one or more antihistamines, one or more steroids, one or more leukotriene antagonists, one or more prostaglandin D2 receptor antagonists, one or more decongestants, one or more expectorants, one or more anti-fungal agents, triamcinolone, one or more non-steroidal immunophilin-dependent immunosuppressants, one or more anti-inflammatory agents, one or more non-steroidal anti-inflammatory agents (NSAIDs), one or more COX-2 inhibitors, one or more anti-infective agents, one or more mucolytic agents, one or more anticholinergic agents, one or more mast cell stabilizers, one or more non-antibiotic anti-microbial agents, one or more anti-viral agents, one or more antiseptics, one or more neurokinin antagonists, platelet activating factor and one or more 5-lipoxygenase (5-LO) inhibitors.

49. The unit dosage form of claim 48, wherein said one or more steroids are selected from the group consisting of fluoromethalone, fluticasone, mometas one, triamcinolone, betamethasone, flunisolide, budesonide, beclomethasone, rimexolone, loteprednol, beloxil, prednisone and dexamethasone, and pharmaceutically acceptable conjugates, salts, esters, variants or derivatives thereof.

50. The unit dosage form of claim 49, wherein said steroid is fluticasone or a pharmaceutically acceptable conjugate, salt, ester, variant or derivative thereof.

51. The unit dosage form of claim 49, wherein said steroid is selected from the group consisting of fluticasone propionate, fluticasone dipropionate, fluticasone fuorate, fluticasone maleate and fluticasone valerate.

52. The unit dosage form of claim 48, wherein said one or more leukotriene antagonists are selected from the group consisting of albuterol sulfate, aminophylline, amoxicillin, ampicillin, astemizole, attenuated tubercle bacillus, azithromycin, bacampicillin, beclomethasone dipropionate, budesonide, bupropion hydrochloride, cefaclor, cefadroxil, cefixime, cefprozil, cefuroxime axetil, cephalexin, ciprofloxacin hydrochloride, clarithromycin, clindamycin, cloxacillin, doxycycline, erythromycin, ethambutol, fenoterol hydrobromide, fluconazole, flunisolide, fluticasone propionate, formoterol fumarate, gatifloxacin, influenza virus vaccine, ipratropium bromide, isoniazid, isoproterenol hydrochloride, itraconazole, ketoconazole, ketotifen, levofloxacin, minocycline, montelukast, moxifloxacin, nedocromil sodium, nicotine, nystatin, ofloxacin, orciprenaline, oseltamivir, oseltamivir sulfate, oxtriphylline, penicillin, pirbuterol acetate, pivampicillin, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, prednisone, pyrazinamide, rifampin, salbutamol, salmeterol xinafoate, sodium cromoglycate, terbutaline sulfate, terfenadine, theophylline, triamcinolone acetonide, zafirlukast and zanamivir.

53. The unit dosage form of claim 48, wherein said pharmaceutical composition comprises one or more prostaglandin D2 receptor antagonists.

54. The unit dosage form of claim 48, wherein said one or more decongestants are selected from the group consisting of pseudoephedrine, phenylephedrine, phenylephrine, phenylpropanolamine, oxymetazoline, propylhexedrine, xylometazoline, epinephrine, ephedrine, desoxyephedrine, naphazoline, and tetrahydrozoline.

55. The unit dosage form of claim 48, wherein said one or more expectorants are selected from the group consisting of guaifenesin, sodium cromoglycate, codeine phosphate and isoproternol hydrochloride.

56. The unit dosage form of claim 48, wherein said one or more anti-fungal agents are selected from the group consisting of amphotericin B, nystatin, fluconazole, ketoconazole, terbinafine, itraconazole, imidazole, triazole, ciclopirox, clotrimazole, and miconazole.

57. The unit dosage form of claim 48, wherein said pharmaceutical composition comprises a triamcinolone or one or more triamcinolone derivatives.

58. The unit dosage form of claim 48, wherein said one or more non-steroidal anti-inflammatory agents are selected from the group consisting of ibuprofen, diclofenac, aceclofenac, 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.

59. The unit dosage form of claim 48, wherein said one or more non-steroidal immunophilin-dependent immunosuppressants (NsIDIs) are selected from the group consisting of cyclosporine, tacrolimus, ascomycin, pimecrolimus, rapamycin, everolimus, and other agents that inhibit calcineurin.

60. The unit dosage form of claim 48, wherein said one or more COX-2 inhibitors are selected from the group consisting of rofecoxib, celecoxib, valdecoxib, lumiracoxib, meloxicam, and nimesulide.

61. The unit dosage form of claim 48, wherein said one or more anti-infective agents are selected from the group consisting of penicillin, beta lactam antibiotics, cephalosporins, macrolides, ketolides, sulfonamides, quinolones, aminoglycosides, cefuroxime, vancomycin, amoxicillin, gentamicin and linezolid.

62. The unit dosage form of claim 48, wherein said one or more mucolytic agents are selected from the group consisting of acetylcysteine and dornase alpha.

63. The unit dosage form of claim 48, wherein said pharmaceutical composition comprises one or more anticholinergic agents selected from the group consisting of mivacurium, atracurium, fazadinium, rocuronium, vecuronium, doxacurium, metocurine, pancuronium, pipecuronium, gallamine, hexafluoronium, suxamethonium, succinylcholine, decamethonium, atropine, scopolamine, hyoscyamine, benzatropine, trihexyphenidyl, biperiden, glycopyrrolate, ipratropium, pirenzepine, telenzepine, tiotropium, darifenacin, vedaclidine, tropicamide, cyclopentolate, dicycloverine, tolterodine, oxybutynin, homatropine, orphenadrine, diphenhydramine, hemicholinium-3, vesamicol, pralidoxime, obidoxime, oxitropium, alcuronium, dimethyltubocurarine, tubocurarine and ipratropium.

64. The unit dosage form of claim 48, wherein said one or more mast cell stabilizers are selected from the group consisting of cromolyn and nedcromil sodium.

65. The unit dosage form of claim 48, wherein said one or more non-antibiotic anti-microbial agents is taurolidine.

66. The unit dosage form of claim 48, wherein said pharmaceutical composition comprises one or more anti-viral agents are selected from the group consisting of abacavir, acyclovir, adefovir, amantadine, amprenavir, arbidol, atazanavir, atripla boceprevir, cidofovir, combivir, darunavir delavirdine, didanosine, docosanol, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fomivirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, ibacitabine, immunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitor, lamivudine, lopinavir, loviride, maraviroc, moroxydine, nelfinavir, nevirapine nexavir, oseltamivir, peginterferon alfa-2a, penciclovir, peramivir, pleconaril, podophyllotoxin, raltegravir, ribavirin, rimantadine, ritonavir, saquinavir, stavudine, tenofovir, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir and zidovudine.

67. The unit dosage form of claim 48, wherein said one or more antiseptics are selected from the group consisting of iodine, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide.

68. The unit dosage form of claim 48, wherein said one or more neurokinin antagonists are selected from the group consisting of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazolines, quinolines, isoquinolines, azanorbornanes, naphthyridines and benzodiazepines.

69. The unit dosage form of claim 48, wherein said one or more 5-lipoxygenase inhibitors are selected from the group consisting of zileuton, docebenone, piripost and tenidap.

70. A unit dosage form comprising a unit dosage container made of high density polyethylene, said unit dosage form having a volume of less than about 0.6 ml and said dosage container having a volume of less than about 1.0 ml containing about 0.1% to about 0.15% azelastine HCl, about 0.05% to about 0.15% sucralose and about 1% to about 10% sorbitol.

71. A unit dosage form comprising a unit dosage container made of high density polyethylene, said unit dosage form having a volume of less than about 0.6 ml and said dosage container having a volume of less than about 1.0 ml containing about 0.15% azelastine HCl, about 0.15% sucralose and about 5% to about 10% sorbitol.

72. A method for treating a physical disorder or a symptom thereof, said method comprising:

(a) providing a unit dosage form of a pharmaceutical formulation comprising a unit dosage container made of high density polyethylene containing a pharmaceutical composition in a volume of less than about 0.6 ml, said container having a volume of less than about 1.0 ml and said pharmaceutical composition comprising one or more antihistamines or pharmaceutically acceptable salts thereof;

(b) administering the pharmaceutical composition in said unit dosage form to a subject in need thereof; and

(c) discarding said unit dosage container.

73. The method of claim 72, wherein said pharmaceutical composition is administered to the eye or ocular mucosa of the subject.

74. The method of claim 72, wherein said pharmaceutical composition is administered to the nasal passage or nasal mucosa of the subject.

75. The method of claim 72, wherein said pharmaceutical composition is administered to the ear.

76. The method of claim 72, wherein said physical disorder is an allergic condition selected from the group consisting of allergic conjunctivitis and allergic rhinitis.

77. The method of claim 72, wherein said physical disorder is allergic conjunctivitis, and wherein the unit dosage form is administered to the eye of the subject.

78. The method of claim 72, wherein said antihistamine is azelastine hydrochloride.

79. The method of claim 72, further comprising one more pharmaceutically acceptable carriers or diluents.

80. The method of claim 72, further comprising one or more additional active pharmaceutical ingredients.

81. The method of claim 80, wherein said one or more additional active pharmaceutical ingredients is selected from the group consisting of one or more antihistamines, one or more steroids, one or more leukotriene antagonists, one or more prostaglandin D2 receptor antagonists, one or more decongestants, one or more expectorants, one or more anti-fungal agents, triamcinolone, one or more non-steroidal immunophilin-dependent immunosuppressants, one or more anti-inflammatory agents, one or more non-steroidal anti-inflammatory agents (NSAIDs), one or more COX-2 inhibitors, one or more anti-infective agents, one or more mucolytic agents, one or more anticholinergic agents, one or more mast cell stabilizers, one or more non-antibiotic anti-microbial agents, one or more anti-viral agents, one or more antiseptics, one or more neurokinin antagonists, platelet activating factor and one or more 5-lipoxygenase (5-LO) inhibitors.

82. The method of claim 81, wherein said one or more steroids are selected from the group consisting of fluoromethalone, fluticasone, mometasone, triamcinolone, betamethasone, flunisolide, budesonide, beclomethasone, rimexolone, loteprednol, beloxil, prednisone and dexamethasone, and pharmaceutically acceptable conjugates, salts, esters, variants or derivatives thereof.

83. The method of claim 82, wherein said steroid is fluticasone or a pharmaceutically acceptable conjugate, salt, ester, variant or derivative thereof.

84. The method of claim 82, wherein said steroid is selected from the group consisting of fluticasone propionate, fluticasone dipropionate, fluticasone fuorate, fluticasone maleate and fluticasone valerate.

85. The method of claim 81, wherein said one or more leukotriene antagonists are selected from the group consisting of albuterol sulfate, aminophylline, astemizole, azithromycin, dipropionate, bupropion hydrochloride, cefaclor, cefadroxil, cefixime, cefprozil, cefuroxime axetil, cephalexin, clarithromycin, clindamycin, cloxacillin, ethambutol, fenoterol hydrobromide, formoterol fumarate, gatifloxacin, ipratropium bromide, isoniazid, isoproterenol hydrochloride, ketotifen, levofloxacin, montelukast, moxifloxacin, nedocromil sodium, nystatin, ofloxacin, orciprenaline, oseltamivir, oseltamivir sulfate, oxtriphylline, pirbuterol acetate, pyrazinamide, rifampin, salbutamol, salmeterol xinafoate, terbutaline sulfate, terfenadine, theophylline, zafirlukast and zanamivir.

86. The method of claim 81, wherein said pharmaceutical composition comprises one or more prostaglandin D2 receptor antagonists.

87. The method of claim 81, wherein said one or more decongestants are selected from the group consisting of pseudoephedrine, phenylephedrine, phenylephrine, phenylpropanolamine, oxymetazoline, propylhexedrine, xylometazoline, epinephrine, ephedrine, desoxyephedrine, naphazoline, and tetrahydrozoline.

88. The method of claim 81, wherein said one or more expectorants are selected from the group consisting of guaifenesin, sodium cromoglycate, codeine phosphate and isoproternol hydrochloride.

89. The method of claim 81, wherein said one or more anti-fungal agents are selected from the group consisting of amphotericin B, nystatin, fluconazole, ketoconazole, terbinafine, itraconazole, imidazole, triazole, ciclopirox, clotrimazole, and miconazole.

90. The method of claim 81, wherein said pharmaceutical composition comprises a triamcinolone or one or more triamcinolone derivatives.

91. The method of claim 81, wherein said one or more non-steroidal anti-inflammatory agents are selected from the group consisting of ibuprofen, diclofenac, aceclofenac, 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.

92. The method of claim 81, wherein said one or more non-steroidal immunophilin-dependent immunosuppressants (NsIDIs) are selected from the group consisting of cyclosporine, tacrolimus, ascomycin, pimecrolimus, rapamycin, everolimus, and other agents that inhibit calcineurin.

93. The method of claim 81, wherein said one or more COX-2 inhibitors are selected from the group consisting of rofecoxib, celecoxib, valdecoxib, lumiracoxib, meloxicam, and nimesulide.

94. The method of claim 81, wherein said one or more anti-infective agents are selected from the group consisting of penicillin, beta lactam antibiotics, cephalosporins, macrolides, ketolides, sulfonamides, quinolones, aminoglycosides, cefuroxime, vancomycin, amoxicillin, gentamicin and linezolid

95. The method of claim 81, wherein said one or more mucolytic agents are selected from the group consisting of acetylcysteine and dornase alpha.

96. The method of claim 81, wherein said pharmaceutical composition comprises one or more anticholinergic agents selected from the group consisting of mivacurium, atracurium, fazadinium, rocuronium, vecuronium, doxacurium, metocurine, pancuronium, pipecuronium, gallamine, hexafluoronium, suxamethonium, succinylcholine, decamethonium, atropine, scopolamine, hyoscyamine, benzatropine, trihexyphenidyl, biperiden, glycopyrrolate, ipratropium, pirenzepine, telenzepine, tiotropium, darifenacin, vedaclidine, tropicamide, cyclopentolate, dicycloverine, tolterodine, oxybutynin, homatropine, orphenadrine, diphenhydramine, hemicholinium-3, vesamicol, pralidoxime, obidoxime, oxitropium, alcuronium, dimethyltubocurarine, tubocurarine and ipratropium.

97. The method of claim 81, wherein said one or more mast cell stabilizers are selected from the group consisting of cromolyn and nedcromil sodium.

98. The method of claim 81, wherein said one or more non-antibiotic anti-microbial agents is taurolidine.

99. The method of claim 81, wherein said pharmaceutical composition comprises one or more anti-viral agents are selected from the group consisting of abacavir, acyclovir, adefovir, amantadine, amprenavir, arbidol, atazanavir, atripla boceprevir, cidofovir, combivir, darunavir delavirdine, didanosine, docosanol, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fomivirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, ibacitabine, immunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitor, lamivudine, lopinavir, loviride, maraviroc, moroxydine, nelfinavir, nevirapine nexavir, oseltamivir, peginterferon alfa-2a, penciclovir, peramivir, pleconaril, podophyllotoxin, raltegravir, ribavirin, rimantadine, ritonavir, saquinavir, stavudine, tenofovir, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir and zidovudine.

100. The method of claim 81, wherein said one or more antiseptics are selected from the group consisting of iodine, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide.

101. The method of claim 81, wherein said one or more neurokinin antagonists are selected from the group consisting of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazolines, quinolines, isoquinolines, azanorbornanes, naphthyridines and benzodiazepines.

102. The method of claim 81, wherein said one or more 5-lipoxygenase inhibitors are selected from the group consisting of zileuton, docebenone, piripost and tenidap.

103. A method of treating or preventing a physical disorder or condition in a patient comprising administering a unit dosage form comprising azelastine or a pharmaceutically acceptable salt thereof to a subject in need thereof, wherein said physical disorder or condition is selected from the group consisting of postoperative ocular inflammation, acute anterior uveitis, dermatitis/keratitis, allergic blepharitis and keratitis, said method comprising:

(a) providing a unit dosage form of a pharmaceutical formulation comprising a unit dosage container made of high density polyethylene containing a pharmaceutical composition in a volume of less than about 0.6 ml, said container having a volume of less than about 1.0 ml and said pharmaceutical composition comprising one or more antihistamines or pharmaceutically acceptable salts thereof;

(b) administering the pharmaceutical composition in said unit dosage form to a subject in need thereof; and

(c) discarding said unit dosage container.

104. A high density polyethylene (HDPE) unit dosage container containing a formulation for nasal or ocular administration, consisting essentially of a therapeutically effective amount of one or more antihistamines, one or more pharmaceutically acceptable carriers or diluents, sucralose and/or sorbitol, wherein said unit dosage container has a volume of less than about 1.0 ml.

105. The unit dose container of claim 104, wherein said one or more antihistamines is azelastine hydrochloride.

106. The unit dose container of claim 104, further comprising one more pharmaceutically acceptable carriers or diluents.

107. The unit dose container of claim 104, further comprising one or more additional active pharmaceutical ingredients.

108. The unit dosage form of claim 107, wherein said one or more additional active pharmaceutical ingredients is selected from the group consisting of one or more antihistamines, one or more steroids, one or more leukotriene antagonists, one or more prostaglandin D2 receptor antagonists, one or more decongestants, one or more expectorants, one or more anti-fungal agents, triamcinolone, one or more non-steroidal immunophilin-dependent immunosuppressants, one or more anti-inflammatory agents, one or more non-steroidal anti-inflammatory agents (NSAIDs), one or more COX-2 inhibitors, one or more anti-infective agents, one or more mucolytic agents, one or more anticholinergic agents, one or more mast cell stabilizers, one or more non-antibiotic anti-microbial agents, one or more anti-viral agents, one or more antiseptics, one or more neurokinin antagonists, platelet activating factor and one or more 5-lipoxygenase (5-LO) inhibitors.

109. The unit dosage form of claim 108, wherein said one or more steroids are selected from the group consisting of fluoromethalone, fluticasone, mometasone, triamcinolone, betamethasone, flunisolide, budesonide, beclomethasone, rimexolone, loteprednol, beloxil, prednisone and dexamethasone, and pharmaceutically acceptable conjugates, salts, esters, variants or derivatives thereof.

110. The unit dosage form of claim 109, wherein said steroid is fluticasone or a pharmaceutically acceptable conjugate, salt, ester, variant or derivative thereof.

111. The unit dosage form of claim 109, wherein said steroid is selected from the group consisting of fluticasone propionate, fluticasone dipropionate, fluticasone fuorate, fluticasone maleate and fluticasone valerate.

112. The unit dosage form of claim 109, wherein said one or more leukotriene antagonists are selected from the group consisting of albuterol sulfate, aminophylline, amoxicillin, ampicillin, astemizole, attenuated tubercle bacillus, azithromycin, bacampicillin, beclomethasone dipropionate, budesonide, bupropion hydrochloride, cefaclor, cefadroxil, cefixime, cefprozil, cefuroxime axetil, cephalexin, ciprofloxacin hydrochloride, clarithromycin, clindamycin, cloxacillin, doxycycline, erythromycin, ethambutol, fenoterol hydrobromide, fluconazole, flunisolide, fluticasone propionate, formoterol fumarate, gatifloxacin, influenza virus vaccine, ipratropium bromide, isoniazid, isoproterenol hydrochloride, itraconazole, ketoconazole, ketotifen, levofloxacin, minocycline, montelukast, moxifloxacin, nedocromil sodium, nicotine, nystatin, ofloxacin, orciprenaline, oseltamivir, oseltamivir sulfate, oxtriphylline, penicillin, pirbuterol acetate, pivampicillin, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, prednisone, pyrazinamide, rifampin, salbutamol, salmeterol xinafoate, sodium cromoglycate, terbutaline sulfate, terfenadine, theophylline, triamcinolone acetonide, zafirlukast and zanamivir.

113. The unit dosage form of claim 109, wherein said pharmaceutical composition comprises one or more prostaglandin D2 receptor antagonists.

114. The unit dosage form of claim 109, wherein said one or more decongestants are selected from the group consisting of pseudoephedrine, phenylephedrine, phenylephrine, phenylpropanolamine, oxymetazoline, propylhexedrine, xylometazoline, epinephrine, ephedrine, desoxyephedrine, naphazoline, and tetrahydrozoline.

115. The unit dosage form of claim 109, wherein said one or more expectorants are selected from the group consisting of guaifenesin, sodium cromoglycate, codeine phosphate and is oproternol hydrochloride.

116. The unit dosage form of claim 109, wherein said one or more anti-fungal agents are selected from the group consisting of amphotericin B, nystatin, fluconazole, ketoconazole, terbinafine, itraconazole, imidazole, triazole, ciclopirox, clotrimazole, and miconazole.

117. The unit dosage form of claim 109, wherein said pharmaceutical composition comprises a triamcinolone or one or more triamcinolone derivatives.

118. The unit dosage form of claim 109, wherein said one or more non-steroidal anti-inflammatory agents are selected from the group consisting of ibuprofen, diclofenac, aceclofenac, 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.

119. The unit dosage form of claim 109, wherein said one or more non-steroidal immunophilin-dependent immunosuppressants (NsIDIs) are selected from the group consisting of cyclosporine, tacrolimus, ascomycin, pimecrolimus, rapamycin, everolimus, and other agents that inhibit calcineurin.

120. The unit dosage form of claim 109, wherein said one or more COX-2 inhibitors are selected from the group consisting of rofecoxib, celecoxib, valdecoxib, lumiracoxib, meloxicam, and nimesulide.

121. The unit dosage form of claim 109, wherein said one or more anti-infective agents are selected from the group consisting of penicillin, beta lactam antibiotics, cephalosporins, macrolides, ketolides, sulfonamides, quinolones, aminoglycosides, cefuroxime, vancomycin, amoxicillin, gentamicin and linezolid

122. The unit dosage form of claim 109, wherein said one or more mucolytic agents are selected from the group consisting of acetylcysteine and dornase alpha.

123. The unit dosage form of claim 109, wherein said pharmaceutical composition comprises one or more anticholinergic agents selected from the group consisting of mivacurium, atracurium, fazadinium, rocuronium, vecuronium, doxacurium, metocurine, pancuronium, pipecuronium, gallamine, hexafluoronium, suxamethonium, succinylcholine, decamethonium, atropine, scopolamine, hyoscyamine, benzatropine, trihexyphenidyl, biperiden, glycopyrrolate, ipratropium, pirenzepine, telenzepine, tiotropium, darifenacin, vedaclidine, tropicamide, cyclopentolate, dicycloverine, tolterodine, oxybutynin, homatropine, orphenadrine, diphenhydramine, hemicholinium-3, vesamicol, pralidoxime, obidoxime, oxitropium, alcuronium, dimethyltubocurarine, tubocurarine and ipratropium.

124. The unit dosage form of claim 109, wherein said one or more mast cell stabilizers are selected from the group consisting of cromolyn and nedcromil sodium.

125. The unit dosage form of claim 109, wherein said one or more non-antibiotic anti-microbial agents is taurolidine.

126. The unit dosage form of claim 109, wherein said pharmaceutical composition comprises one or more anti-viral agents are selected from the group consisting of abacavir, acyclovir, adefovir, amantadine, amprenavir, arbidol, atazanavir, atripla boceprevir, cidofovir, combivir, darunavir delavirdine, didanosine, docosanol, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fomivirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, ibacitabine, immunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitor, lamivudine, lopinavir, loviride, maraviroc, moroxydine, nelfinavir, nevirapine nexavir, oseltamivir, peginterferon alfa-2a, penciclovir, peramivir, pleconaril, podophyllotoxin, raltegravir, ribavirin, rimantadine, ritonavir, saquinavir, stavudine, tenofovir, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir and zidovudine.

127. The unit dosage form of claim 109, wherein said one or more antiseptics are selected from the group consisting of iodine, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide.

128. The unit dosage form of claim 109, wherein said one or more neurokinin antagonists are selected from the group consisting of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazolines, quinolines, isoquinolines, azanorbornanes, naphthyridines and benzodiazepines.

129. The unit dosage form of claim 109, wherein said one or more 5-lipoxygenase inhibitors are selected from the group consisting of zileuton, docebenone, piripost and tenidap.