Dry powder drug delivery system

• US 10,342,938 B2
• Filed: 06/14/2016
• Issued: 07/09/2019
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Smutney, Chad C., Adamo, Benoit, Polidoro, John M., Kinsey, P. Spencer, Overfield, Dennis, Sahi, Carl R., Billings, Christine, Marino, Mark T.
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US15/182,503
• Publication Number:
  US 20160287820A1
• Time in Patent Office: 1,120 Days
• CPC Class Codes: A61K 38/28 Insulins
• 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 15/0028 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 15/0091 mechanically breath-triggered
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/6081 Colour codes
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

A pulmonary drug delivery system is disclosed, including a breath-powered, dry powder inhaler, and 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, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of endocrine disease, for example, diabetes and/or obesity.

Claims

1. A dry powder inhaler comprising:

a flow path through a container within the dry powder inhaler, wherein said flow path generates a resistance to flow of the dry powder inhaler which is relatively constant across a pressure differential range of between 0.5 kPa and 7 kPa and said resistance to flow in a dosing configuration ranges in value from about 0.065 to about 0.200 (√

kPa)/liter/min;

wherein the container comprises a cartridge comprising a lid and a cup in a dosing configuration and includes a dry powder formulation comprising a diketopiperazine, and wherein after a single inhalation the diketopiperazine in a subject'"'"'s plasma has an AUC_0-∞

greater than 2,300 ng*min/mL but less than or about 5,500 ng*min/mL per mg of the diketopiperazine content in the dry powder formulation.

2. The dry powder inhaler of claim 1, wherein the container is removable from the dry powder inhaler.

3. The dry powder inhaler of claim 1, wherein the container is reconfigurable in the dry powder inhaler from a containment configuration to a dosing configuration.

4. The dry powder inhaler of claim 1, wherein the diketopiperazine particles include

5. The dry powder inhaler of claim 1, wherein the diketopiperazine has a T_max of less than 1 hour.

6. The dry powder inhaler of claim 1, wherein the dry powder formulation includes a pharmaceutically active ingredient.

7. The dry powder inhaler of claim 6, wherein the active ingredient is selected from the group consisting of a peptide, polypeptide, protein, and a combination thereof.

8. The dry powder inhaler of claim 6, wherein the active ingredient is selected from the group consisting of insulin, glucagon-like peptide 1, oxyntomodulin, peptide YY, exendin, heparin, calcitonin, felbamate, sumatriptan, parathyroid hormone, growth hormone, erythropoietin, zidovudine, didanosine, granulocyte macrophage colony stimulating factor, lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, beta-galactosidase, exendin, vasoactive intestinal peptide, argatroban, anti-SSX-241-49 (synovial sarcoma, X breakpoint 2), anti-NY-ESO-1 (esophageal tumor associated antigen), anti-PRAME (preferentially expressed antigen of melanoma), anti-PSMA (prostate-specific membrane antigen), anti-Melan-A (melanoma tumor associated antigen), anti-tyrosinase (melanoma tumor associated antigen), and a combination thereof.

17. The dry powder inhaler of claim 1, wherein the container is removable from the dry powder inhaler.

18. The dry powder inhaler of claim 1, wherein the container is reconfigurable in the dry powder inhaler from a containment configuration to a dosing configuration.

19. The dry powder inhaler of claim 1, wherein the diketopiperazine has a T_max of less than 1 hour.

9. A dry powder inhaler comprising:

a flow path through a container comprising a cartridge comprising a lid and a cup in a dosing configuration and within the dry powder inhaler wherein said flow path generates a resistance to flow of the dry powder inhaler which is relatively constant across a pressure differential range of between 0.5 kPa and 7 kPa and said resistance to flow in a dosing configuration ranges in value from about 0.065 to about 0.200 (√

kPa)/liter/min,

wherein the container includes a dry powder formulation comprising a diketopiperazine and wherein the inhaler is operably configured to emit a powder plume comprising the diketopiperazine having a volumetric median geometric diameter from 2 μ

m to 8 μ

m, and

wherein the flow path through the container consists of 20% to 70% of the total airflow through the inhaler.

10. The dry powder inhaler of claim 9, wherein the container is removable from the dry powder inhaler.

11. The dry powder inhaler of claim 9, wherein the container is reconfigurable in the dry powder inhaler from a containment configuration to a dosing configuration.

12. The dry powder inhaler of claim 9, wherein the diketopiperazine particles include

13. The dry powder inhaler of claim 9, wherein the diketopiperazine has a T_max of less than 1 hour.

14. The dry powder inhaler of claim 9, wherein the dry powder formulation includes a pharmaceutically active ingredient.

15. The dry powder inhaler of claim 14, wherein the active ingredient is selected from the group consisting of a peptide, polypeptide, protein, and a combination thereof.

16. The dry powder inhaler of claim 14, wherein the active ingredient is selected from the group consisting of insulin, glucagon-like peptide 1, oxyntomodulin, peptide YY, exendin, heparin, calcitonin, felbamate, sumatriptan, parathyroid hormone, growth hormone, erythropoietin, zidovudine, didanosine, granulocyte macrophage colony stimulating factor, lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, beta-galactosidase, exendin, vasoactive intestinal peptide, argatroban, anti-SSX-241-49 (synovial sarcoma, X breakpoint 2), anti-NY-ESO-1 (esophageal tumor associated antigen), anti-PRAME (preferentially expressed antigen of melanoma), anti-PSMA (prostate-specific membrane antigen), anti-Melan-A (melanoma tumor associated antigen), anti-tyrosinase (melanoma tumor associated antigen), and a combination thereof.