Dry powder inhaler and system for drug delivery

• US 9,192,675 B2
• Filed: 07/30/2013
• Issued: 11/24/2015
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mankind
• Inventors: Smutney, Chad C., Kinsey, P. Spencer, Sahi, Carl R., Adamo, Benoit, Polidoro, John M., McLean, Scott, Overfield, Dennis, Kraft, Kelly S., Somerville, Karla
• Primary Examiner(s): GHALI, ISIS A D
• Application Number:
  US13/954,731
• Publication Number:
  US 20130338065A1
• Time in Patent Office: 847 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 drug delivery system comprising an inhaler, a powder container, comprising fumaryl diketopiperazine (FDKP) microparticles comprising a trans-FDKP isomer content of about 45% to about 65% and a drug, wherein the aerodynamic performance of the microparticles is improved as compared to fumaryl diketopiperazine microparticles having a trans isomer content outside of said trans isomer content of about 45% to about 65%;

and

wherein in use about 10% to 70% of an air flow exiting the inhaler and entering a user passes through the powder container and about 90% to 30% of said air flow bypasses the powder container.

2. The drug delivery system of claim 1 wherein the FDKP microparticles have a trans-FDKP isomer content of about 45% to about 56%.

3. The drug delivery system of claim 1 wherein said powder container comprises a unit dose cartridge.

4. The drug delivery system of claim 1 wherein the FDKP microparticles comprise a drug comprising insulin, GLP-1, heparin, calcitonin, felbamate, parathyroid hormone and fragments thereof, oxyntomodulin, growth hormone, erythropoietin, AZT, DDI, G-CSF, lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, β

-galactosidase or Argatroban.

5. The drug delivery system of claim 1 having a resistance to flow of about 0.065 to about 0.200 (√

kPa)/liter per minute.

6. The drug delivery system of claim 4 wherein the drug is insulin.

7. The drug delivery system of claim 6 wherein the insulin content of the FDKP microparticles is about 3 to about 4 U/mg.

8. A method of treating an insulin-related disorder comprising providing, for self-administration, the drug delivery system of claim 1 to administer insulin to a person in need thereof.

13. The drug delivery system of claim 1 wherein the FDKP microparticles are prepared by a process comprising recrystallizing FDKP from a solvent, then forming microparticles, wherein the trans-FDKP content of the microparticles is about 45% to about 65%.

14. The drug delivery system of claim 13 wherein the FDKP microparticles have a trans-FDKP isomer content of about 50% to about 65%.

15. The drug delivery system of claim 13 wherein the FDKP microparticles have a trans-FDKP isomer content of about 54% to about 65%.

16. The drug delivery system of claim 4 having a manufacturing specification in a range of about 53% to about 63% trans-FDKP isomer content, based upon the total content of FDKP.

17. The drug delivery system of claim 15 wherein the FDKP microparticles have a trans-FDKP isomer content of about 54% to about 63%.

18. The drug delivery system of claim 17 wherein the FDKP microparticles have a trans-FDKP isomer content of about 54% to about 56%.

9. A drug delivery system comprising an inhaler, a powder container comprising FDKP microparticles having improved aerodynamic performance that have been prepared by a process comprising determining the trans-FDKP isomer content;

wherein the microparticles have a trans-FDKP isomer content of about 45% to about 65% and the aerodynamic performance of the microparticles is improved as compared to fumaryl diketopiperazine microparticles having a trans isomer content outside of said trans isomer content of about 45% to about 65%; and

wherein in use about 10% to 70% of an air flow exiting the inhaler and entering a user passes through the powder container and about 90% to 30% of said air flow bypasses the powder container.

10. The drug delivery system of claim 9 comprising FDKP microparticles having a trans-FDKP isomer content of about 50% to about 63%.

11. The drug delivery system of claim 9 comprising FDKP microparticles having a trans-FDKP isomer content of about 45% to about 56%.

12. The drug delivery system of claim 9 having a resistance to flow of approximately 0.065 to about 0.200 (IkPa)/liter per minute.