Dry powder drug delivery system

• US 20100197565A1
• Filed: 03/04/2010
• Published: 08/05/2010
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Marino, Mark T., Overfield, Dennis, Billings, Christine, Smutney, Chad C., Adamo, Benoit, Kinsey, P. Spencer, Polidoro, John M., Sahi, Carl R.
• Granted Patent: US 8,485,180 B2
• Time in Patent Office: Days
• US Class Current: 514/1.1
• 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 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. An inhalation system, comprising:

a dry powder inhaler; and

a dry powder formulation comprising a plurality of powder particles of a diketopiperazine;

wherein the inhalation system is configured to deliver the diketopiperazine to the pulmonary circulation of a subject, and said diketopiperazine is measured in a subject'"'"'s plasma having an AUC_0-∞

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

2. The inhalation system of claim 1, further comprising a cartridge configured to adapt to said dry powder inhaler.

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

4. The inhalation system of claim 3, wherein the diketopiperazine is bis-3,6-(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine.

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

6. The inhalation system of claim 2, wherein the cartridge containing a dry powder formulation is reconfigurable in the inhaler from a containment configuration to a dosing configuration.

7. The inhalation system of claim 4, wherein the bis-3,6-(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine has a T_max of less than 1 hour.

8. The inhalation system of claim 5, wherein the active ingredient is a protein, a peptide, a polypeptide or fragments thereof.

9. The inhalation system of claim 5, wherein the active ingredient is insulin.

10. An inhalation system, comprising:

a dry powder inhaler, and

a dry powder formulation comprising a plurality of diketopiperazine particles;

wherein the inhalation system is operably configured to emit a powder plume comprising the diketopiperazine microparticles 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.

11. The inhalation system of claim 10, further comprising a cartridge for adapting to said dry powder inhaler.

12. The inhalation system of claim 10, wherein the dry powder inhaler is a breath powered inhaler.

13. The inhalation system of claim 10, wherein the diketopiperazine is bis-3,6-(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine.

14. The inhalation system of claim 10, wherein the dry powder formulation comprises an active ingredient.

15. The inhalation system of claim 14, wherein the active ingredient is a protein, a peptide, a polypeptide or fragments thereof.

16. The inhalation system of claim 14, wherein the active ingredient is insulin.

17. An inhalation system for pulmonary delivery of a drug, comprising:

a breath-powered dry powder inhaler, and

a dry powder formulation comprising a plurality of diketopiperazine particles;

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

18. An inhalation system, comprising:

a dry powder inhaler; and

a dry powder formulation comprising a plurality of dry powder particles comprising insulin;

wherein the inhalation system is configured to deliver the insulin to the pulmonary circulation of a subject, and said insulin can be measured in a subject'"'"'s plasma at an exposure having a AUC_{0-2 hr} greater than 160 uU*min/mL per unit of insulin emitted in the dry powder formulation administered in a single inhalation.

19. The inhalation system of claim 18, wherein a C_max for insulin is measured in less than 30 minutes after administration to a patient by oral inhalation.

20. The inhalation system of claim 18, wherein the powder formulation comprises a diketopiperazine.

21. The inhalation system of claim 19, wherein the diketopiperazine is bis-3,6-(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine.