Nasal administration

Patent metadata

Field	Value
Publication number	US-9649456-B2
Application number	US-59436508-A
Country	US
Kind code	B2
Filing date	Apr 7, 2008
Priority date	Apr 5, 2007
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

A delivery device for and method of delivering a powdered substance, in particular a triptan, such as sumatriptan, to the posterior region of a nasal cavity of a subject, in particular for the treatment of headaches, for example, cluster headaches and migraine, and neuropathic pain, the delivery device comprising: a nosepiece ( 47 ) for insertion into a nasal cavity of a subject through which the powdered substance is delivered to the posterior region of the nasal cavity of the subject, in particular the upper posterior two thirds of the nasal cavity; and a substance supply unit ( 16 ) which is operable to deliver the powdered substance through the nosepiece ( 47 ).

First claim

The invention claimed is:

1. A method of treating migraine in a human subject by delivering a powdered substance comprising sumatriptan to the posterior region of a nasal cavity of the human subject, the method comprising:
inserting a nosepiece into the nasal cavity of the human subject;
inserting a mouthpiece into the mouth of the human subject;
the subject exhaling through the mouthpiece to cause closure of the oropharyngeal velum of the subject, wherein the mouthpiece is fluidly connected to the nosepiece, whereby exhaled air from an exhalation breath is delivered through the nosepiece; and
delivering the powdered substance through the nosepiece to the posterior region of the nasal cavity of the subject via a bi-directional flow through the nasal cavity, wherein the powdered substance is delivered from a container chamber which houses a container which contains the powdered substance, and the container chamber includes an inlet which is fluidly connected to the mouthpiece and an outlet which is fluidly connected to the nosepiece, whereby exhaled air from the exhalation breath acts to entrain the powdered substance and deliver the powdered substance through the nosepiece;
wherein the powdered substance consists essentially of sumatriptan succinate without introduced excipients or adjuvants and;
wherein the powdered substance has an untapped bulk density of between about 0.3 g/ml and about 0.5 g/ml;
wherein the powdered substance comprises a particle size distribution of 10% less than about 20 μm, 50% less than about 50 μm, and 90% less than about 150 μm.

2. The method of claim 1 , wherein the container comprises a capsule formed from a cellulose derivative, hydroxypropyl methylcellulose (HPMC) or a gelatine derivative.

3. The method of claim 1 , wherein the nosepiece is configured, when inserted into the nasal cavity, to extend into the nasal valve and provide for expansion of the nasal valve.

4. The method of claim 1 , wherein the nosepiece is configured to obstruct the nasal valve or to close the nasal valve and thereby substantially prevent deposition of the powdered substance anteriorly of the nasal valve.

5. The method of claim 1 , wherein the powdered substance has a tapped bulk density of between about 0.5 g/ml and about 0.75 g/ml.

6. The method of claim 1 , wherein the container contains a 10 mg dose of the powdered substance.

7. The method of claim 1 , wherein the ratio of the nasal absorption fraction to total bio-availability (BA) is greater than about 1.

8. The method of claim 1 , wherein the ratio of the nasal absorption fraction to total bio-availability (BA) is greater than about 1.5.

9. The method of claim 1 , wherein the ratio of the nasal absorption fraction to total bio-availability (BA) is greater than about 2.

10. The method of claim 1 , wherein the powdered substance has an untapped bulk density of about 0.4 g/ml.

11. The method of claim 1 , wherein the powdered substance has a tapped bulk density of about 0.63 g/ml.

12. The method of claim 1 , wherein the container is a capsule, the method further comprising the step of piercing the capsule before delivering the substance.

13. The method of claim 1 , wherein the container is a capsule.

14. The method of claim 1 , wherein a time maximum plasma concentration T max is achieved that is less than about 25 minutes and has a peak plasma concentration C max of at least 10 ngml −1 .

15. A method of treating migraine in a human subject by delivering a powdered sumatriptan substance to a posterior region of a nasal cavity of the subject, comprising:
inserting a nosepiece into a nostril of the subject;
closing the oropharyngeal velum of the subject; and
delivering the powdered sumatriptan substance through the nosepiece to the posterior region of the nasal cavity of the subject via a bi-directional air flow through the nasal cavity of the subject, wherein the powdered sumatriptan substance is delivered from a substance containing unit which contains the powdered sumatriptan substance, and the substance containing unit includes an inlet and an outlet which is fluidly connected to the nosepiece, whereby the bi-directional air flow is delivered through the inlet of the substance containing unit and acts to entrain the powdered sumatriptan substance and deliver the powdered sumatriptan substance from the outlet and through the nosepiece;
wherein the powdered sumatriptan substance has an untapped bulk density of between about 0.3 g/ml and about 0.5 g/ml; and
wherein the powdered sumatriptan substance has a particle size distribution of 50% greater than about 30 μm.

16. The method of claim 15 , wherein the powdered sumatriptan substance comprises a sumatriptan base or sumatriptan succinate.

17. The method of claim 15 , wherein the powdered sumatriptan substance contains only sumatriptan succinate and no introduced excipients or adjuvants.

18. The method of claim 15 , wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a substance container.

19. The method of claim 18 , wherein the substance container is a capsule.

20. The method of claim 18 , wherein the substance container contains a 10 mg dose.

21. The method of claim 15 , wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a capsule.

22. The method of claim 15 , wherein the powdered sumatriptan substance has a particle size distribution of 90% greater than about 10 μm, and 10% greater than about 90 μm.

23. A method of treating migraine in a human subject by delivering a powdered sumatriptan substance to a posterior region of a nasal cavity of the subject, comprising:
inserting a nosepiece into a nostril of the subject;
inserting a mouthpiece into a mouth of the subject;
the subject exhaling through the mouthpiece to cause closure of the oropharyngeal velum of the subject, wherein the mouthpiece is fluidly connected to the nosepiece, whereby exhaled air from an exhalation breath is delivered through the nosepiece; and
delivering the powdered sumatriptan substance through the nosepiece to the posterior region of the nasal cavity of the subject via a bi-directional air flow through the nasal cavity of the subject, wherein the powdered sumatriptan substance is delivered from a substance containing unit which contains the powdered sumatriptan substance, and the substance containing unit includes an inlet which is fluidly connected to the mouthpiece and an outlet which is fluidly connected to the nosepiece, whereby exhaled air from the exhalation breath is delivered through the inlet of the substance containing unit and acts to entrain the powdered sumatriptan substance and deliver the powdered sumatriptan substance from the outlet and through the nosepiece;
wherein the powdered sumatriptan substance has an untapped bulk density of between about 0.3 g/ml and about 0.5 g/ml; and
wherein the powdered sumatriptan substance has a particle size distribution of 50% greater than about 30 μm.

24. The method of claim 23 , wherein the powdered sumatriptan substance comprises a sumatriptan base or sumatriptan succinate.

25. The method of claim 23 , wherein the powdered sumatriptan substance contains only sumatriptan succinate and no introduced excipients or adjuvants.

26. The method of claim 23 , wherein the powdered sumatriptan substance to be delivered to the nasal cavity of

Assignees

• Djupesland Per Gisle
• Hafner Roderick Peter
• Optinose As

Inventors

• Djupesland Per Gisle
• Hafner Roderick Peter

Classifications

• A61K31/4045

  Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin · CPC title

• A61M2210/0625

  Mouth · CPC title

• A61M2210/0618

  Nose · CPC title

• A61M2205/3606

  cooled · CPC title

• A61M2202/064

  Powder · CPC title