Compositions comprising azelastine and methods of use thereof

• US 10,064,817 B2
• Filed: 10/28/2011
• Issued: 09/04/2018
• 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: Dang, Phuong Grace, Lawrence, Brian D., Balwani, Gul, D'Addio, Alexander D.
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US13/284,836
• Publication Number:
  US 20120083479A1
• Time in Patent Office: 2,503 Days
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• 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

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.

Claims

1. An intranasal pharmaceutical product, comprising a liquid pharmaceutical composition comprising:

(i) from about 0.05% to about 0.5% (w/v) azelastine hydrochloride, (ii) from about 0.01% to about 1.0% (w/v) fluticasone propionate, and (iii) from about 0.1% to about 0.5% (w/v) sucralose,

wherein the composition in the intranasal pharmaceutical product is formulated for intranasal administration in a human.

2. The intranasal pharmaceutical product of claim 1, further comprising one or more additional active agents selected from the group consisting of one or more decongestants, one or more antihistamines, one or more non-steroidal anti-inflammatory agents and one or more leukotriene antagonists.

3. The intranasal pharmaceutical product of claim 1, wherein said azelastine hydrochloride is present in said composition at a concentration of from about 0.125% to about 0.15% (w/v).

4. The intranasal pharmaceutical product of claim 1, wherein said azelastine hydrochloride is present in said composition at a concentration of from about 0.05% to about 0.15% (w/v).

5. The intranasal pharmaceutical product of claim 1, wherein said liquid pharmaceutical composition is contained within an intranasal delivery system.

6. The intranasal pharmaceutical product of claim 5, wherein said intranasal delivery system comprises a bottle and a pump.

7. The intranasal pharmaceutical product of claim 6, wherein pump is a metered multi-dose pump.

8. The intranasal pharmaceutical product of claim 1, wherein said liquid pharmaceutical composition is in the form of a nasal spray.

9. The intranasal pharmaceutical product of claim 1, wherein said liquid pharmaceutical composition is in the form of nasal drops.

10. The intranasal pharmaceutical product of claim 1, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.07 to about 0.15 ml per spray.

11. The intranasal pharmaceutical product of claim 10, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.14 ml per spray.

12. The intranasal pharmaceutical product of claim 1, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.2% (w/v).

13. The intranasal pharmaceutical product of claim 1, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.15% (w/v).

14. The intranasal pharmaceutical product of claim 1, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.15% (w/v).

15. The intranasal pharmaceutical product of claim 1, wherein said azelastine hydrochloride in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.15% (w/v).

16. The intranasal pharmaceutical product of claim 1, wherein said liquid pharmaceutical composition further comprises sorbitol.

17. The intranasal pharmaceutical product of claim 16, wherein said sorbitol in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 10% (w/v) sorbitol 70%.

18. The intranasal pharmaceutical product of claim 16, wherein said sorbitol in said liquid pharmaceutical composition is present at a concentration of about 6.4% (w/v) sorbitol 70%.

19. A method of treating allergic rhinitis, non-allergic vasomotor rhinitis or allergic conjunctivitis in a human suffering from or predisposed thereto, comprising intranasally administering to said human an effective amount of the intranasal pharmaceutical product of claim 1.

20. The method of claim 19, wherein said liquid pharmaceutical composition is contained within an intranasal delivery system.

21. The method of claim 20, wherein said liquid pharmaceutical composition is in the form of a nasal spray.

22. The method of claim 19, wherein said liquid pharmaceutical composition further comprises sorbitol.

23. The method of claim 19, wherein said liquid pharmaceutical composition is contained within an intranasal delivery system.

24. The method of claim 23, wherein said intranasal delivery system comprises a bottle and a pump.

25. The method of claim 24, wherein said pump is a metered multi-dose pump.

26. The method of claim 19, wherein said liquid pharmaceutical composition is in the form of nasal drops.

27. The method of claim 19, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.07 to about 0.15 ml per spray.

28. The method of claim 27, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.14 ml per spray.

29. The method of claim 19, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.2% (w/v).

30. The method of claim 19, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.15% (w/v).

31. The method of claim 19, wherein said sucralose in said liquid pharmaceutical composition is present at a concentration of about 0.15% (w/v).

32. The method of claim 19, wherein said azelastine hydrochloride in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 0.15% (w/v).

33. The method of claim 19, wherein said liquid pharmaceutical composition further comprises sorbitol.

34. The method of claim 33, wherein said sorbitol in said liquid pharmaceutical composition is present at a concentration of about 0.1% to about 10% (w/v) sorbitol 70%.

35. The method of claim 33, wherein said sorbitol in said liquid pharmaceutical composition is present at a concentration of about 6.4% (w/v) sorbitol 70%.