Dry powder drug delivery system and methods

• US 9,802,012 B2
• Filed: 07/12/2013
• Issued: 10/31/2017
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Smutney, Chad C., Adamo, Benoit, Laurenzi, Brendan F., Kinsey, P. Spencer
• Primary Examiner(s): Scherbel, Todd J
• Assistant Examiner(s): Ruddie, Elliot S
• Application Number:
  US13/941,365
• Publication Number:
  US 20140014106A1
• Time in Patent Office: 1,572 Days
• Field of Search: 12820312, 12820315, 12820319, 12820321, 12820323
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0005 with means for agitating the medicament
• CPC Class Codes: A61M 15/002 with air flow regulating means
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0025 with caps
• 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 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 2016/0027 pressure meter
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/076 mouth operated
• CPC Class Codes: A61M 2206/14 Static flow deviators in tubes disturbing laminar flow in tubes, e.g. archimedes screws
• CPC Class Codes: A61M 2206/16 Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: A61M 2206/20 having means for promoting or enhancing the flow, actively or passively

Abstract

A pulmonary drug delivery system is disclosed, including a breath-powered, dry powder inhaler, with or without a cartridge for delivering a dry powder formulation. The inhaler and cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, small organic molecules, peptides and proteins, including, hormones such as insulin and glucagon-like peptide 1 for the treatment of disease and disorders, for example, diseases and disorders, including endocrine disease such as diabetes and/or obesity.

Claims

1. A dry powder inhaler comprising:

a) a first element comprising a mouthpiece;

b) a second element comprising a cartridge including a powder container and a lid; and

c) at least two rigid air conduits;

wherein one of the at least two rigid air conduits in a dosing configuration includes a deflector or stem protruding from an undersurface of the lid facing an internal volume of the powder container to direct airflow entering the internal volume of the powder container from a direction parallel to the mouthpiece to a substantially downward direction to a direction substantially parallel to the mouthpiece through the dry powder to a direction substantially perpendicular to the mouthpiece to exit the powder container; and

wherein in a containment configuration the dry powder is sealed from the at least two air conduits and from the deflector or stem;

wherein the powder container comprising a first vertical wall and a second vertical wall parallel and opposed;

wherein in the dosing configuration the deflector or stem is disposed between the first vertical wall and the second vertical wall.

2. The dry powder inhaler of claim 1 having a resistance value to airflow ranging from about 0.065 (√

kPa)/liter per minute to about 0.200 (√

kPa)/liter per minute.

3. The dry powder inhaler of claim 1, wherein the dry powder is a formulation for oral inhalation and comprises an amount from about 1 mg to about 50 mg of the dry powder.

4. The dry powder inhaler of claim 3, wherein the dry powder comprises a drug or an active agent.

5. The dry powder inhaler of claim 4, wherein the active agent is an endocrine hormone, vaccines, small molecules, including anti-asthmatics, vasodilators, vasoconstrictors, muscle relaxants, or neurotransmitter agonist or antagonists.

6. The dry powder inhaler of claim 3, wherein the dry powder comprises a peptide, a polypeptide, or fragments thereof, a small organic molecule or a nucleic acid molecule.

7. The dry powder inhaler of claim 6, wherein said peptide is insulin, glucagon, glucagon-like peptide-1, parathyroid hormone, deoxyribonuclease, oxytocin, oxyntomodulin, peptide YY, an exendin, or fragments thereof.

8. The dry powder inhaler of claim 6, wherein the small organic molecule is a vasodialator, a vasoconstrictor, a neurotransmitter agonist or a neurotransmitter antagonist.

9. The dry powder inhaler of claim 8, wherein the small organic molecule is a triptan or an opiate.

10. The dry powder inhaler of claim 9, wherein the triptan is sumatriptan or rizatriptan.

11. The dry powder inhaler of claim 1, wherein the powder container is integrated into a container housing and filled with a dry powder.

12. The dry powder inhaler of claim 1, wherein the powder container is provided separate from the inhaler and is filled with a dry powder.

13. The dry powder inhaler of claim 1, wherein the powder is an amorphous powder.

14. A method of delivering a dry powder to a subject comprising administering to said subject an effective amount of an amorphous powder medicament using the dry powder inhaler of claim 1.

15. The dry powder inhaler of claim 1, wherein the one of the at least two rigid air conduits does not have a cross-sectional O-shape.

16. The dry powder inhaler of claim 1, wherein the dry powder comprises a diketopiperazine or a pharmaceutically acceptable salt thereof.

17. The dry powder inhaler of claim 16, wherein the diketopiperazine is of the formula 2,5-diketo-3,6-bis(N—

X-4-aminobutyl)piperazine, wherein X is selected from the group consisting of fumaryl, succinyl, maleyl, malonyl, oxalyl and glutaryl.

18. The dry powder inhaler of claim 17, wherein the diketopiperazine is 3,6-bis-(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine.

19. A dry powder inhaler comprising:

a) a first element comprising a mouthpiece; and

b) at least two rigid air conduits;

wherein one of the at least two rigid air conduits in a dosing configuration includes a deflector or stem protruding from an undersurface of a lid facing an internal volume of a powder container to direct airflow entering the internal volume of the powder container from a direction parallel to the mouthpiece to a substantially downward direction to a direction substantially parallel to the mouthpiece through the dry powder to a direction substantially perpendicular to the mouthpiece to exit the powder container; and

wherein in a containment configuration the dry powder is sealed from the at least two air conduits and from the deflector or stem;

wherein the powder container comprising a first vertical wall and a second vertical wall parallel and opposed;

wherein in the dosing configuration the deflector or stem is disposed between the first vertical wall and the second vertical wall.