Dry powder drug delivery system

• US 9,393,372 B2
• Filed: 07/02/2013
• Issued: 07/19/2016
• 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:
  US13/933,845
• Publication Number:
  US 20130291867A1
• Time in Patent Office: 1,113 Days
• US Class Current: 1/1
• 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.

Claims

1. An inhalation system, comprising:

a dry powder inhaler comprising;

a mouthpiece and a container, wherein the container comprises a top and a bottom which are moveable relative to one another by a translational motion to create a first flow path, wherein 20% to 70% of total airflow through the inhaler enters and exits the container, and wherein the container includes a dry powder formulation comprising diketopiperazine particles; and

a second flow path wherein 30-80% of total airflow through the inhaler by-passes the container;

wherein the second flow path converges with the first flow path at a substantially perpendicular angle, and

wherein after a single inhalation from the inhalation system, diketopiperazine in a subject'"'"'s plasma has an AUC_0-∞

greater than 2,300 ng*min/mL per mg of the diketopiperazine content in the dry powder formulation.

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

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

4. The inhalation system of claim 1, wherein the dry powder inhaler is a breath powered inhaler.

5. The inhalation system of claim 1, wherein the diketopiperazine particles include

6. The inhalation system of claim 1, wherein the diketopiperazine has a T_max of less than 1 hour.

7. The inhalation system of claim 1, wherein the dry powder formulation includes an active ingredient.

8. The inhalation system of claim 7, wherein the active ingredient is a peptide, polypeptide, protein, or a combination thereof.

9. The inhalation system of claim 7, wherein the active ingredient is insulin, glucagon-like peptide 1, oxyntomodulin, peptide YY, exendin, heparin, calcitonin, felbamate, sumatriptan, parathyroid hormone, growth hormone, erythropoietin, AZT, DDI, granulocyte macrophage colony stimulating factor, lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, beta-galactosidase, exendin, vasoactive intestinal peptide, and argatroban, anti-SSX-2_41-49, anti-NY-ES0-1, anti-PRAME, anti-PSMA, anti-Melan-A, anti-tyrosinase, or a combination thereof.

10. The inhalation system of claim 7, wherein the active ingredient is insulin, glucagon-like peptide 1, oxyntomodulin, peptide YY, exendin, analogs thereof, or a combination thereof.

11. The inhalation system of claim 7, wherein the active ingredient is insulin.

12. The inhalation system of claim 7, wherein the active ingredient is glucagon-like peptide 1.

13. The inhalation system of claim 7, wherein the active ingredient is oxyntomodulin.

14. The inhalation system of claim 1, wherein the inhalation system is operably configured to emit a powder plume comprising the diketopiperazine particles having a volumetric median geometric diameter ranging from 2 μ

m to 8 μ

m and a geometric standard deviation of less than 4 μ

m.

15. The inhalation system of claim 1, wherein the inhalation system is operably configured to emit more than 90% of the dry powder formulation and the diketopiperazine particles dissolve and are absorbed into the blood in less than 30 minutes yielding a peak concentration of the diketopiperazine after the single inhalation.

16. The inhalation system of claim 11, wherein the inhalation system is configured to deliver insulin to the pulmonary circulation of the subject, and the insulin measured at an exposure having a AUC_{0-2 hr} greater than 160 μ

U*min/mL per unit of insulin emitted in the dry powder formulation.

17. The inhalation system of claim 16, wherein an insulin C_max is achieved less than 30 minutes after administration.

18. The inhalation system of claim 1, wherein the first flow path is sheared by the second flow path when the first flow path exits the container.

19. An inhalation system, comprising:

a dry powder inhaler comprising;

a mouthpiece and a container, wherein the container includes a dry powder formulation comprising diketopiperazine particles;

a first flow path wherein 20% to 70% of total airflow through the inhaler enters and exits the container; and

a second flow path wherein 30-80% of total airflow through the inhaler by-passes the container;

wherein the first flow path exits the container substantially perpendicularly to the second flow path and is sheared by the second flow path; and

wherein after a single inhalation from the inhalation system, diketopiperazine in a subject'"'"'s plasma has an AUC_0-∞

greater than 2,300 ng*min/mL per mg of the diketopiperazine content in the dry powder formulation.

20. An inhalation system, comprising:

a dry powder inhaler comprising;

a mouthpiece and a container, wherein the container comprises a top and a bottom which are moveable relative to one another by a translational motion, wherein the container includes a dry powder formulation comprising diketopiperazine particles, and wherein the container does not include an air conduit resulting from puncturing or peeling;

a first flow path wherein 20% to 70% of total airflow through the inhaler enters and exits the container; and

a second flow path wherein 30-80% of total airflow through the inhaler by-passes the container;

wherein after a single inhalation from the inhalation system, diketopiperazine in a subject'"'"'s plasma has an AUC_0-∞

greater than 2,300 ng*min/mL per mg of the diketopiperazine content in the dry powder formulation.