Buccal, polar and non-polar spray containing zolpidem

• US 7,632,517 B2
• Filed: 09/29/2003
• Issued: 12/15/2009
• Est. Priority Date: 10/01/1997
• Status: Expired due to Fees

• Current Assignee: Magna Pharmaceuticals, Inc.
• Original Assignee: NovaDel Pharma Inc.
• Inventors: Dugger, Harry A. III, Abd El-Shafy, Mohammed
• Primary Examiner(s): Haghighatian; Mina
• Application Number:
  US10/671,715
• Publication Number:
  US 20040265239A1
• Time in Patent Office: 2,269 Days
• Field of Search: 424/435, 424/45, 514/923
• US Class Current: 424/435
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• 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 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives

Abstract

Buccal aerosol sprays or capsules using polar and non-polar solvents have now been developed which provide zolpidem for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, zolpidem, and optional flavoring agent; formulation II: aqueous polar solvent, zolpidem, optionally flavoring agent, and propellant; formulation III: non-polar solvent, zolpidem, and optional flavoring agent; formulation IV: non-polar solvent, zolpidem, optional flavoring agent, and propellant; formulation V: a mixture of a polar solvent and a non-polar solvent, zolpidem, and optional flavoring agent; formulation VI: a mixture of a polar solvent and a non-polar solvent, zolpidem, optional flavoring agent, and propellant.

Claims

1. A method of treating insomnia in a human patient, comprising:

providing an oral spray composition comprising zolpidem or a pharmaceutically acceptable salt thereof in an amount of between 2.5 and 20 percent by weight of the total composition;

a polar solvent in an amount between 15 and 60 percent by weight of the total composition; and

water; and

spraying the composition on the oral mucosa of the patient to provide transmucosal absorption of an amount of zolpidem through the oral mucosa to the systemic circulatory system of the patient sufficient to treat the patient'"'"'s insomnia.

2. The method of claim 1, wherein the composition further comprises a taste mask and/or flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.

3. The method of claim 1, wherein the zolpidem or a pharmaceutically acceptable salt thereof is present in an amount between 2.5 and 15 percent by weight of the total composition.

4. The method of claim 1, wherein the zolpidem or a pharmaceutically acceptable salt thereof is present in an amount between 2.5 and 10 percent by weight of the total composition.

5. The method of claim 1, wherein the pharmaceutically acceptable salt thereof is zolpidem tartrate.

6. The method of claim 1, wherein the polar solvent is present in an amount between 25 and 50 percent by weight of the total composition.

7. The method of claim 1, wherein the polar solvent is present in an amount between 30 and 45 percent by weight of the total composition.

8. The method of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.

9. The method of claim 1, wherein the polar solvent is polyethylene glycol.

10. The method of claim 1, wherein the polar solvent is ethanol.

11. The method of claim 1, wherein the polar solvent is propylene glycol.

12. The method of claim 1, wherein the composition comprises a flavoring agent selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.

13. The method of claim 1, wherein the amount of the spray is predetermined.

14. The method of claim 1, wherein the composition is propellant free.

15. The method of claim 1, wherein the composition further comprises a buffer.

16. The method of claim 1, wherein the composition comprises zolpidem tartrate and propylene glycol.

17. The method of claim 16, wherein the zolpidem tartrate is present in an amount between 2.5 and 10 percent by weight of the total composition.

18. The method of claim 17, wherein the propylene glycol is present in an amount between 20 and 45 percent by weight of the total composition.

19. The method of claim 18, further comprising a buffer.

20. The method of claim 19, further comprising a flavorant or taste masking agent.

21. The method of claim 20, wherein the composition is propellant free.