Compositions comprising azelastine and methods of use thereof

• US 8,071,073 B2
• Filed: 11/22/2005
• Issued: 12/06/2011
• 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): Fetterolf, Brandon
• Assistant Examiner(s): Heyer, Dennis
• Application Number:
  US11/284,109
• Publication Number:
  US 20060110331A1
• Time in Patent Office: 2,205 Days
• Field of Search: 514/217.05, 424/45, 424/464
• 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 liquid pharmaceutical composition for treating allergic rhinitis or non-allergic vasomotor rhinitis, said liquid pharmaceutical composition comprising:

about 0.100% (w/v) azelastine hydrochloride;

about 0.100% (w/v) of hypromellose;

about 0.05% (w/v) disodium edetate;

about 0.025% (w/v) benzalkonium chloride 50% solution, NF;

about 0.150% (w/v) sucralose;

about 6.4% (w/v) sorbitol 70%;

about 0.068% (w/v) sodium citrate dihydrate; and

QS water,

wherein said liquid pharmaceutical composition is formulated in the form of a nasal spray or nasal drops.

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

5. The liquid pharmaceutical composition of claim 4, wherein said intranasal delivery system comprises a bottle and a pump.

6. The liquid pharmaceutical composition of claim 5, wherein said pump is a metered multi-dose pump.

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

16. The liquid pharmaceutical composition of claim 13, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.07 ml to about 0.15 ml per spray.

17. The liquid pharmaceutical composition of claim 13, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.14 ml per spray.

2. A liquid pharmaceutical composition for treating allergic rhinitis or non-allergic vasomotor rhinitis, said liquid pharmaceutical composition comprising:

about 0.1% to about 0.15% (w/v) azelastine hydrochloride;

about 0.1% to about 0.15% (w/v) sucratose; and

about 0.1% to about 10% (w/v) sorbitol 70%,

wherein said liquid pharmaceutical composition is formulated in the form of a nasal spray or nasal, drops.

7. The liquid pharmaceutical composition of claim 2, wherein said liquid pharmaceutical composition is contained within an intranasal delivery system.

8. The liquid pharmaceutical composition of claim 7, wherein said intranasal delivery system comprises a bottle and a pump.

9. The liquid pharmaceutical composition of claim 8, wherein said pump is a metered multi-dose pump.

14. The liquid pharmaceutical composition of claim 2, wherein said liquid pharmaceutical composition is in the form of a nasal spray.

18. The liquid pharmaceutical composition of claim 14, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.07 ml to about 0.15 ml per spray.

19. The liquid pharmaceutical composition of claim 14, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.14 ml per spray.

22. The liquid pharmaceutical composition of claim 2, wherein said liquid pharmaceutical composition further comprises:

hypromellose;

disodium edetate;

benzalkonium chloride 50% solution, NF;

sodium citrate dihydrate; and

QS water.

23. The liquid pharmaceutical composition of claim 2, wherein said liquid pharmaceutical composition further comprises:

about 0.001% to about 5.00% (w/v) of hypromellose;

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

about 0.001% to about 0.5% (w/v) benzalkonium chloride 50% solution, NF;

about 0.068% (w/v) sodium citrate dihydrate; and

QS water.

24. The liquid pharmaceutical composition of claim 2, wherein the concentration of sorbitol in said liquid pharmaceutical composition is sufficient for the osmolality of said liquid pharmaceutical composition to be from about 220 mOsmol/kg to about 350 mOsmol/kg.

26. The liquid pharmaceutical composition of claim 24, wherein the concentration of sorbitol in said liquid pharmaceutical composition is sufficient for the osmolality of said liquid pharmaceutical composition to be from about 250 mOsmol/kg to about 320 mOsmol/kg.

28. The liquid pharmaceutical composition of claim 2, wherein said liquid pharmaceutical composition comprises sucralose at a concentration of about 0.15% (w/v).

3. A liquid pharmaceutical composition for treating allergic rhinitis or non-allergic vasomotor rhinitis, said liquid pharmaceutical composition comprising:

about 0.150% (w/v) azelastine hydrochloride;

about 0.100% (w/v) of hypromellose;

about 0.05% (w/v) disodium edetate;

about 0.001% to about 0.5% (w/v) benzalkonium chloride 50% solution, NF;

about 0.150% (w/v) sucralose;

about 0.1% to about 10% (w/v) sorbitol 70%;

about 0.068% (w/v) sodium citrate dihydrate; and

QS water,

wherein said liquid pharmaceutical composition is formulated in the form of a nasal spray or nasal drops.

10. The liquid pharmaceutical composition of claim 3, wherein said liquid pharmaceutical composition is contained within an intranasal delivery system.

11. The liquid pharmaceutical composition of claim 10, wherein said intranasal delivery system comprises a bottle and a pump.

12. The liquid pharmaceutical composition of claim 11, wherein said pump is a metered multi-dose pump.

15. The liquid pharmaceutical composition of claim 3, wherein said liquid pharmaceutical composition is in the form of a nasal spray.

20. The liquid pharmaceutical composition of claim 15, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.07 ml to about 0.15 m1 per spray.

21. The liquid pharmaceutical composition of claim 15, wherein said liquid pharmaceutical composition is formulated to intranasally deliver a volume of said composition of about 0.14 ml per spray.

25. The liquid pharmaceutical composition of claim 3, wherein the concentration of sorbitol in said liquid pharmaceutical composition is sufficient for the osmolality of said liquid pharmaceutical composition to be from about 220 mOsmol/kg to about 350 mOsmol/kg.

27. The liquid pharmaceutical composition of claim 25, wherein the concentration of sorbitol in said liquid pharmaceutical composition is sufficient for the osmolality of said liquid pharmaceutical composition to be from about 250 mOsmol/kg to about 320 mOsmol/kg.