Dry powder inhaler and system for drug delivery

• US 8,424,518 B2
• Filed: 06/12/2009
• Issued: 04/23/2013
• 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, McLean, Scott, Overfield, Dennis, Bryant, Anthony, Polidoro, John M.
• Primary Examiner(s): Anderson, Lynne
• Application Number:
  US12/484,137
• Publication Number:
  US 20090308392A1
• Time in Patent Office: 1,411 Days
• Field of Search: 128/203.15
• US Class Current: 128/203.15
• 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 dry powder medicament cartridge for an inhaler, comprising:

an enclosure configured to hold a medicament comprising a cartridge top and a cartridge bottom which are moveable relative to one another by a translational motion;

at least one inlet port to allow flow into the enclosure, and

at least one dispensing port to allow flow out of the enclosure;

said at least one inlet port is configured to direct at least a portion of the flow entering the

at least one inlet port at the at least one dispensing port within the enclosure in response to a pressure differential.

2. The dry powder medicament cartridge of claim 1, wherein the dry powder medicament cartridge is formed from a polymer material.

3. The cartridge of claim 2, wherein the polymer material is a thermoformable plastic selected from the group consisting of a polypropylene, a cyclicolephin co-polymer, a nylon and a polyethylene.

4. The cartridge of claim 2, wherein the dry powder medicament cartridge is formed from a high density polyethylene polymer.

5. The cartridge of claim 1, wherein the cartridge bottom has an internal surface defining an internal volume and comprising a bottom and side walls contiguous with one another, and having one or more openings.

6. The cartridge of claim 5, wherein the cartridge bottom has a cup-like structure and has one opening with a rim.

7. The cartridge of claim 1, wherein the cartridge top and the cartridge bottom are configurable to have one or more inlet ports and one or more dispensing ports.

8. The cartridge of claim 1, wherein the cartridge top and cartridge bottom are configurable to a containment positionor a dispensing or dosing position.

9. The cartridge of claim 8, wherein the cartridge top and the cartridge bottom are further configurable to have a discarding position.

10. The cartridge of claim 8, wherein the containment position restricts fluid communication to internal volume and the dispensing or dosing position forms an air passage entering the one or more inlet ports through the internal volume in the container and exiting the one or more openings in the cartridge top.

11. The cartridge of claim 7, wherein the one or more openings of the cartridge top form rigid conduits and form the one or more dispensing ports of the dry powder medicament cartridge.

12. The cartridge of claim 6, wherein a portion of the rim forms a border for one of the one or more inlet ports.

13. The cartridge of claim 1, wherein the pressure differential is generated by an inhalation by a user when installed in the inhaler.

14. The cartridge of claim 1, further comprising a powder composition comprising an active ingredient.

15. The cartridge of claim 14 wherein the active ingredient is a peptide, polypeptide, or protein.

16. The cartridge of claim 15 wherein the active ingredient is insulin.

17. The cartridge of claim 14, wherein the powder composition comprises a diketopiperazine.

18. The cartridge of claim 17, wherein the diketopiperazine is

19. A dry powder medicament cartridge for a dry powder inhaler, comprising:

a cartridge top and a cartridge bottom defining an internal volume;

wherein the cartridge top or the cartridge bottom are moveable relative to one another by a translational motion;

wherein the cartridge top has an undersurface that extends over the cartridge bottom;

said undersurface configured to engage said cartridge bottom, and having an area to seal the internal volume and an area to expose the internal volume to ambient air.

20. The dry powder medicament cartridge of claim 19, wherein the dry powder medicament cartridge is formed from a thermoformable polymer selected from the group consisting of a polypropylene, a cyclicolephin co-polymer, a nylon and a polyethylene.

21. The dry powder medicament cartridge of claim 19, wherein the dry powder medicament cartridge is formed from a high density polyethylene polymer.

22. The dry powder medicament cartridge of claim 19, wherein the cartridge bottom has an inner surface defining the internal volume and comprises a bottom and side walls contiguous with one another, and one or more openings.

23. The dry powder medicament cartridge of claim 19, wherein the cartridge top undersurface is configured to close the cartridge bottom at a section and form an air passage into the internal volume at another section.

24. The dry powder medicament cartridge of claim 19, wherein the cartridge top and the container are configurable to have one or more inlet ports and one or more dispensing ports.

25. The dry powder medicament cartridge of claim 24, wherein the one or more inlet ports has a total cross-sectional area which is larger than a total cross-sectional area of the dispensing ports.

26. The dry powder medicament cartridge of claim 24, wherein the cross-sectional area of the one or more dispensing ports ranges from 0.05 cm² to about 0.25 cm².

27. The dry powder medicament cartridge of claim 19, wherein the cartridge top and cartridge bottom are configurable to a containment position, a dispensing or dosing position.

28. The dry powder medicament cartridge of claim 27, wherein the cartridge top and cartridge bottom are further configurable to a discarding position.

29. The dry powder medicament cartridge of claim 27, wherein the containment position restricts fluid communication to internal volume and the dispensing or dosing position forms an air passage from the one or more inlet ports through the internal volume with the one or more openings in the cartridge top.

30. The dry powder medicament cartridge of claim 19, wherein the one or more openings of the cartridge top form rigid conduits and the one or more dispensing ports of the inhaler cartridge.

31. The dry powder medicament cartridge of claim 19, wherein the one or more inlet ports is configured to direct at least part of a flow into the cartridge to the one or more dispensing ports.

32. The dry powder medicament cartridge of claim 19, further comprising a powder composition comprising an active ingredient.

33. The dry powder medicament cartridge of claim 32, wherein the active ingredient is a peptide, polypeptide, or protein.

34. The dry powder medicament cartridge of claim 33, wherein the active ingredient is insulin.

35. The dry powder medicament cartridge of claim 32, wherein the powder composition comprises a diketopiperazine.

36. The dry powder medicament cartridge of claim 35, wherein the diketopiperazine is

37. A dry powder medicament cartridge for a dry powder inhaler, comprising a cartridge top and a cartridge bottom;

the cartridge top configured relatively flat and having one or more openings and one or side panels having tracks configured to engage the cartridge bottom;

wherein the cartridge top has an undersurface configured to have a relatively flat surface and provide closure of the internal volume at one end and to provide a flow conduit at the opposing end;

said cartridge bottom having an inner surface defining an internal volume and is moveably attached to the tracks on the one or more side panels on the cartridge top and configurable to attain a containment position and a dispensing or dosing position by moving along the tracks of the one or more side panels.

38. The medicament cartridge of claim 37, wherein the cartridge top and the cartridge bottom in the dispensing or dosing position form an inlet port that allows fluid communication with the chamber of the container and therethrough with the one or more openings in the cartridge top.

39. The medicament cartridge of claim 37, wherein in the dispensing dosing position, the chamber is in fluid communication with the one or more openings in the cartridge top and ambient air at least at two openings.

40. The medicament cartridge of claim 37, wherein in the dispensing or dosing position, the inlet port is configured to direct part of a flow into the internal volume to circulate the flow about the internal volume.

41. The medicament cartridge of claim 37, wherein in the dispensing or dosing position, the one or more openings in the cartridge top are the dispensing ports of the cartridge and provide resistance to flow.

42. The medicament cartridge of claim 37, wherein the cartridge top comprises one or more keying surfaces.

43. The medicament cartridge of claim 37, wherein the cartridge top is relatively rectangular in shape, comprising a recessed area on its upper surface and a boss having the one or more openings.

44. The medicament cartridge of claim 37, wherein the cartridge top further comprises grasping surfaces.

45. The medicament cartridge of claim 37, wherein the cartridge in the dosing position has an inlet port substantially rectangular and comprising a width greater than 0.2 cm and a height greater than 0.05 cm.

46. The medicament cartridge of claim 37, wherein the cartridge bottom has a width ranging from 0.4 cm to 1.2 cm and a height ranging from 0.6 cm to 1.2 cm.

47. The medicament cartridge of claim 38, wherein in use in the dispensing position with an inhaler a portion of a flow entering an inlet aperture circulates within the internal volume to lift and entrain a powder medicament and a portion of the flow exits through a dispensing aperture.

48. The medicament cartridge of claim 37, wherein the cartridge bottom holds up to about 20 mg of a powder composition.

50. The medicament cartridge of claim 48, wherein the powder composition comprises an active ingredient.

51. The cartridge of claim 50 wherein the active ingredient is a peptide, polypeptide, or protein.

52. The cartridge of claim 51 wherein the active ingredient is insulin.

53. The medicament cartridge of claim 48, wherein the powder composition comprises a diketopiperazine.

54. The medicament cartridge of claim 53, wherein the diketopiperazine is

55. The medicament cartridge of claim 52, wherein the insulin comprises up to 9 units of insulin per mg of powder.

56. The medicament cartridge of claim 48, wherein cartridge comprises one or more colors or markings to identify the powder composition.

49. A dry powder medicament cartridge for an inhaler, comprising an enclosure comprising a cartridge top and a cartridge bottom which are moveable relative to one another by a translational motion and having one or more exit ports configured to have a smallest dimension less than 3 mm to exclude release of larger powder aggregates.

57. The medicament cartridge of claim 49, further comprising a powder composition comprising an active ingredient.

58. The medicament cartridge of claim 57, wherein the active ingredient is a peptide, polypeptide, or protein.

59. The medicament cartridge of claim 58, wherein the active ingredient is insulin.

60. The medicament cartridge of claim 57, wherein the powder composition comprises a diketopiperazine.

61. The medicament cartridge of claim 60, wherein the diketopiperazine is

62. A dry powder medicament cartridge for an inhaler comprising:

a substantially flat cartridge top, arrow-like in configuration, having one or more dispensing apertures, and two side panels extending downwardly and each of the two side panels having a track; and

a cartridge bottom moveably engaged to the track of the side panels of the cartridge top, and comprising a chamber configured having a relatively cup-like shape with two relatively flat and parallel sides and a relatively rounded bottom, and interior surface defining an internal volume, which promotes tumbling of a flow entering the internal volume;

said container configurable to attain a containment position and a dosing position with said cartridge top

wherein the cartridge top and the cartridge bottom are moveable relative to one another by a translational motion.

63. The cartridge of claim 62, wherein the cartridge further comprises a dry powder medicament and in use with a dry powder inhaler in the dosing position promotes air flow entering an inlet aperture to mix with the medicament to fluidize the medicament.

64. The cartridge of claim 63, wherein fluidized medicament moves within the enclosure such that the fluidized medicament is metered through the one or more dispensing apertures.

65. The cartridge of claim 62, wherein the flow entering the internal volume is non-vortical, with an axis defining a center of rotation being substantially perpendicular to flow exiting the one or more dispensing apertures.

66. The cartridge of claim 65, wherein the non-vortical flow of air in the internal volume acts to de-agglomerate a medicament.

67. The cartridge of claim 63, wherein the dry powder medicament comprises an active ingredient.

68. The cartridge of claim 67, wherein the active ingredient is a peptide, polypeptide, or protein.

69. The cartridge of claim 68, wherein the active ingredient is insulin.

70. The cartridge of claim 67, wherein the dry powder medicament comprises a diketopiperazine.

71. The cartridge of claim 70, wherein the diketopiperazine is