Nasal administration

• US 9,649,456 B2
• Filed: 04/07/2008
• Issued: 05/16/2017
• Est. Priority Date: 04/05/2007
• Status: Active Grant

• Current Assignee: OptiNose, Inc.
• Original Assignee: OptiNose AS (OptiNose, Inc.)
• Inventors: Djupesland, Per Gisle, Hafner, Roderick Peter
• Primary Examiner(s): Woodward, Valerie L
• Application Number:
  US12/594,365
• Publication Number:
  US 20100288275A1
• Time in Patent Office: 3,326 Days
• Field of Search: 12820024, 12820312, 12820315, 12820316, 12820317, 12820318, 12820319, 12820321, 12820322, 12820323
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61M 15/0005 with means for agitating the medicament
• CPC Class Codes: A61M 15/0008 rotating by airflow
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/003 using capsules, e.g. to be perforated or broken-up
• CPC Class Codes: A61M 15/0035 Piercing means
• CPC Class Codes: A61M 15/0041 with movable piercing or cutting means
• CPC Class Codes: A61M 15/0098 Activated by exhalation
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 16/0808 Condensation traps
• CPC Class Codes: A61M 16/1045 Devices for humidifying or heating the inspired gas by using recovered moisture or heat from the expired gas
• CPC Class Codes: A61M 16/1055 bacterial
• CPC Class Codes: A61M 16/1065 in the expiratory path
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/3606 cooled
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 2210/0625 Mouth

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).

Claims

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 μ

m, 50% less than about 50 μ

m, and 90% less than about 150 μ

m.

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 μ

m.

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 μ

m, and 10% greater than about 90 μ

m.

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 μ

m.

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 the subject is disposed in a substance container.

27. The method of claim 26, wherein the substance container is a capsule.

28. The method of claim 26, wherein the substance container contains a 10 mg dose.

29. The method of claim 23, wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a capsule.

30. The method of claim 23, wherein the powdered sumatriptan substance has a particle size distribution of 90% greater than about 10 μ

m, and 10% greater than about 90 μ

m.

31. A device for delivering a powdered sumatriptan substance to a posterior region of a nasal cavity of a subject, comprising:

a nosepiece configured for fitting to a nostril of the subject; and

a substance containing unit connected to the nosepiece, the substance containing unit comprising the powdered sumatriptan substance to be delivered to the nasal cavity of the subject, 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 μ

m;

wherein the device is configured such that, when the nosepiece is fitted to the nostril of the subject, oral exhalation by the subject through the substance containing unit and the nosepiece acts to close the oropharyngeal velum of the subject and produce an exhalation flow passing into one nasal passage of the subject and out of the other nasal passage of the subject, thereby achieving a bi-directional exhalation flow for delivering the powdered sumatriptan substance to the posterior region of the nasal cavity of the subject.

32. The device of claim 31, wherein the powdered sumatriptan substance comprises a sumatriptan base or sumatriptan succinate.

33. The device of claim 31, wherein the powdered sumatriptan substance contains only sumatriptan succinate and no introduced excipients or adjuvants.

34. The device of claim 31, wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a substance container.

35. The device of claim 34, wherein the substance container is a capsule.

36. The device of claim 34, wherein the substance container contains a 10 mg dose.

37. The device of claim 31, wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a capsule.

38. The device of claim 31, wherein the powdered sumatriptan substance has a particle size distribution of 90% greater than about 10 μ

m, and 10% greater than about 90 μ

m.

39. A device for delivering a powdered sumatriptan substance to a posterior region of a nasal cavity of a subject, comprising:

a mouthpiece configured for fitting to an oral cavity of the subject;

a nosepiece configured for fitting to a nostril of the subject; and

a substance containing unit connected to the nosepiece, the substance containing unit comprising the powdered sumatriptan substance to be delivered to the nasal cavity of the subject, 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 μ

m;

wherein the device is configured such that, when the nosepiece is fitted to the nostril of the subject and the mouthpiece is fitted to the oral cavity of the subject, oral exhalation by the subject through the mouthpiece acts to close the oropharyngeal velum of the subject and produce an exhalation air flow which entrains the powdered sumatriptan substance, passes into one nasal passage of the subject and out of the other nasal passage of the subject, thereby achieving a bi-directional exhalation flow for delivering the powdered sumatriptan substance to the posterior region of the nasal cavity of the subject.

40. The device of claim 39, wherein the powdered sumatriptan substance comprises a sumatriptan base or sumatriptan succinate.

41. The device of claim 39, wherein the powdered sumatriptan substance contains only sumatriptan succinate and no introduced excipients or adjuvants.

42. The device of claim 39, wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a substance container.

43. The device of claim 42, wherein the substance container is a capsule.

44. The device of claim 42, wherein the substance container contains a 10 mg dose.

45. The device of claim 39, wherein the powdered sumatriptan substance to be delivered to the nasal cavity of the subject is disposed in a capsule.

46. The device of claim 39, wherein the powdered sumatriptan substance has a particle size distribution of 90% greater than about 10 μ

m, and 10% greater than about 90 μ

m.