Dry powder inhaler and system for drug delivery

• US 9,511,198 B2
• Filed: 11/27/2013
• Issued: 12/06/2016
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Smutney, Chad C., Kinsey, P. Spencer, Sahi, Carl R., Adamo, Benoit, Polidoro, John M., McLean, Scott, Overfield, Dennis, Bryant, Anthony, He, Tom, Mann, Alfred
• Primary Examiner(s): Anderson, Lynne
• Application Number:
  US14/092,810
• Publication Number:
  US 20140083421A1
• Time in Patent Office: 1,105 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0023 retractable
• 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 15/0043 Non-destructive separation of the package, e.g. peeling
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0048 the dosages being arranged in a plane, e.g. on diskettes
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/6081 Colour codes
• CPC Class Codes: A61M 2206/20 having means for promoting or enhancing the flow, actively or passively

Abstract

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Claims

1. A method of treatment using a dry powder medicament to be delivered to the pulmonary tract with a dry powder inhalation system, comprising:

opening a dry powder inhaler having a mouthpiece;

loading a cartridge comprising a pre-metered dose of a dry powder medicament in a containment configuration;

closing the inhaler to reconfigure the cartridge to a dosing configuration, wherein in the dosing configuration the inhaler is configured to have at least two inlet apertures, wherein a first inlet aperture is in communication with a first air flow pathway and a second inlet aperture is in communication with a second air flow pathway, and the first airflow pathway and the second airflow pathway converge in a substantially perpendicular manner during an inhalation maneuver; and

inhaling once through the mouthpiece to deliver the dry powder medicament in a single inhalation.

2. The method of claim 1 wherein the dry powder medicament comprises an active agent.

3. The method of claim 2 wherein the active agent comprises at least one of a synthetic organic compound, a protein, a peptide, a sugar, a lipid, an inorganic compound, or a nucleic acid sequence.

4. The method of claim 1 wherein the dry powder medicament comprises a microparticle.

5. The method of claim 4 wherein the microparticle comprises a diketopiperazine.

6. The method of claim 5 wherein the diketopiperazine has the formula 3,6-di(4-X-aminobutyl)-2,5-diketopiperazine, wherein X is selected from the group consisting of fumaryl, succinyl, maleyl, and glutaryl.

7. The method of claim 6 wherein the diketopiperazine is 3,6-di(4-fumaryl-aminobutyl)-2,5-diketopiperazine.

8. The method of claim 5 wherein the microparticle comprises an active agent.

9. The method of claim 8 wherein the active agent comprises as least one of a hormone, an anticoagulant, an immunomodulating agent, a vaccine, a cytotoxic agent, an antibiotic, a vasoactive agent, a neuroactive agent, an anesthetic, a sedative, a steroid, a decongestant, an antiviral, an antisense molecule, an antigen, or an antibody or fragment thereof.

10. The method of claim 8 wherein the active agent comprises as least one of insulin or an analog thereof, GLP-1 or an analog thereof, heparin, calcitonin, felbamate, sumatriptan, parathyroid hormone and active fragments thereof, growth hormone, erythropoietin, AZT, DDI, granulocyte macrophage colony stimulating factor (GM-CSF), lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, β

-galactosidase, exendin, vasoactive intestinal peptide, and argatroban.

11. The method of claim 10 wherein the active agent comprises insulin or an analog thereof.

12. The method of claim 10 wherein the active agent comprises GLP-1 or an analog thereof.

13. A method of de-agglomerating a powder medicament in a dry powder inhalation system, comprising:

providing the dry powder medicament in a container having an internal volume to a dry powder inhaler configured to have at least two inlet apertures, wherein a first inlet aperture is in communication with a first air flow pathway and a second inlet aperture is in communication with a second air flow pathway, and the first airflow pathway and the second airflow pathway converge in a substantially perpendicular manner during an inhalation maneuver, wherein closing said inhaler reconfigures said inhaler into a dosing configuration;

allowing a flow to enter said container which is configured to direct a flow to lift, entrain and circulate the dry powder medicament until the powder medicament comprises individual particles and particle aggregates sufficiently small to pass through one or more dispensing apertures into a mouthpiece.

14. The method of claim 13, further comprising the step of accelerating the powder particles and/or particle aggregates entrained in the flow leaving the one or more dispensing apertures and entering the mouthpiece.

15. The method of claim 13 wherein the dry powder medicament comprises an active agent.

16. The method of claim 15 wherein the active agent comprises at least one of a synthetic organic compound, a protein, a peptide, a sugar, a lipid, an inorganic compound, or a nucleic acid sequence.

17. The method of claim 16 wherein the dry powder medicament comprises a microparticle.

18. The method of claim 17 wherein the microparticle comprises a diketopiperazine.

19. The method of claim 18 wherein the diketopiperazine has the formula 3,6-di(4-X-aminobutyl)-2,5-diketopiperazine, wherein X is selected from the group consisting of fumaryl, succinyl, maleyl, and glutaryl.

20. The method of claim 19 wherein the active agent comprises insulin or an analog thereof.

21. The method of claim 20 wherein the diketopiperazine is 3,6-di(4-fumaryl-aminobutyl)-2,5-diketopiperazine.