Dry powder inhalers, related blister package indexing and opening mechanisms, and associated methods of dispensing dry powder substances

• US 7,451,761 B2
• Filed: 10/21/2004
• Issued: 11/18/2008
• Est. Priority Date: 10/27/2003
• Status: Expired due to Fees

• Current Assignee: Oriel Therapeutics, Inc. (Novartis Ag)
• Original Assignee: Oriel Therapeutics, Inc. (Novartis Ag)
• Inventors: Fording, Jay Kinsley, Warden, Jeffrey Alan, Hickey, Anthony James, Riley, William Myles, Rockwell, Paul Gilbert, Ferris, Bruce Seymour, Anderson, Sean Derek, Crowder, Timothy, Garten, Michael Duane, Johnson, Keith Arthur, Ketner, Mark Ennis
• Primary Examiner(s): Yu; Justine R
• Assistant Examiner(s): Matter; Kristen C
• Application Number:
  US10/970,154
• Publication Number:
  US 20050103337A1
• Time in Patent Office: 1,489 Days
• Field of Search: 128/203.15, 128/203.12, 128/203.19, 128/203.21, 128/200.14, 128/200.21
• US Class Current: 128/203.21
• CPC Class Codes: A61M 15/001 using ultrasonic means
• CPC Class Codes: A61M 15/0023 retractable
• CPC Class Codes: A61M 15/0038 Cutting means
• 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 15/0078 on a strip
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0081 Locking means
• CPC Class Codes: A61M 15/0083 Timers
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/18 with alarm
• CPC Class Codes: A61M 2205/43 making noise when used correctly
• CPC Class Codes: A61M 2205/44 making noise when used incorrectly
• CPC Class Codes: A61M 2205/581 by audible feedback
• CPC Class Codes: A61M 2205/584 having a color code

Abstract

Dry powder inhalers with a multi-dose dry powder package for dispensing pharmaceutical grade formulations of inhalable dry powder, include: (a) a blister package comprising a plurality of spaced apart sealed blisters thereon, each blister having a projecting ceiling and a floor defining a blister channel therebetween, the blister channel comprising a dry powder therein; (b) a movable blade cartridge holding a blade at a forward portion thereof; and (c) an extendable mouthpiece attached to the movable blade cartridge. In operation, a user pulls the mouthpiece outward and then pushes the mouthpiece inward to cause the blister package to advance to position a blister in a selected dispensing position in the inhaler and to cause the blade cartridge to move the blade across a blister ceiling held in the dispensing position in the inhaler to thereby open the blister held in the dispensing position.

Claims

1. A dry powder inhaler with a multi-dose dry powder package for dispensing pharmaceutical grade formulations of inhalable dry powder, comprising:

an inhaler housing;

a blister package held in the housing, the blister package comprising a plurality of spaced apart sealed blisters thereon, each blister having a projecting ceiling and a floor defining a blister channel therebetween, the blister channel comprising a dry powder therein;

a blister indexing mechanism in communication with the blister package to position a blister in a dispensing position;

a movable blade cartridge mounted in the housing configured to hold a blade at a forward portion thereof; and

an extendable mouthpiece attached to the movable blade cartridge, wherein, in operation, a user extends the mouthpiece outward and then retracts the mouthpiece inward to cause the blister package to advance thereby positioning a blister in the dispensing position in the inhaler, the retraction causing the blade cartridge to move the blade lengthwise across a blister ceiling held in the dispensing position in the inhaler to open the blister held in the dispensing position.

2. A dry powder inhaler according to claim 1, wherein the blister channels have a width, depth, and length, and wherein the blade is configured to travel in the inhaler above and across at least a major portion of the length of a respective channel, substantially horizontally.

3. A dry powder inhaler according to claim 1, wherein, in operation, a forwardmost portion of the blade stops traveling inward into the inhaler before the blade reaches an innermost edge portion of blister.

4. A dry powder inhaler according to claim 1, wherein, in operation, a forwardmost portion of the blade travels beyond the innermost edge portion of the blister.

5. A dry powder inhaler according to claim 1, wherein the indexing mechanism comprises a rotatable gear that cooperates with the mouthpiece and the blister package to advance the blister package a desired distance to position a blister in the dispensing position in the inhaler.

6. A dry powder inhaler according to claim 5, wherein the indexing mechanism further comprises a pawl that is attached to the mouthpiece and positioned in the inhaler so as to engage the gear and rotate the blister package a predetermined distance to serially advance blisters toward the dispensing position when the mouthpiece is extended outward.

7. A dry powder inhaler according to claim 5, wherein the indexing mechanism includes a gear window sized and configured to hold the gear therein, wherein the pawl is located about an outer perimeter of one side of the gear window and configured and sized so as to contact and advance at least one gear tooth forward when the mouthpiece is extended outward.

8. A dry powder inhaler according to claim 7, further comprising a locking arm extending into the gear window and configured to abut a portion of a gear tooth of the gear at a position that is spaced apart from the pawl to inhibit the gear from rotating backward when the mouthpiece is retracted inward.

9. A dry powder inhaler according to claim 8, wherein the pawl is configured to engage the gear in one rotating direction only when the mouthpiece is extended and to disengage the gear when the mouthpiece is retracted.

10. A dry powder inhaler according to claim 5, wherein the blister package is circular, wherein the gear is a rotatable gear substantially centrally mounted on a substantially rigid blister frame, the gear and frame being attached to the blister package to form a disposable blister and gear package assembly that is replaceable in the inhaler when the dry powder in the blisters on the package has been dispensed.

11. A dry powder inhaler according to claim 10, wherein the substantially rigid blister frame comprises apertures sized and configured to allow the projected ceilings of the blister package to extend therethrough.

12. A dry powder inhaler according to claim 1, wherein the blade cartridge has a plow-shaped forward edge portion.

13. A dry powder inhaler according to claim 12, wherein the plow-shaped forward edge portion has a leading cutting edge portion with a lateral portion that spans out horizontally and a vertical portion that rises at an angle of greater than about 30 degrees.

14. A dry powder inhaler according to claim 12, wherein the blade cartridge has a body with a flow channel formed therein, and wherein, in operation, dry powder flows through from the opened blister through the blade cartridge flow channel to the user.

15. A dry powder inhaler according to claim 1, wherein the blister package comprises a foil-containing ceiling having sufficient rigidity to be formed into and retain the ceiling projection shapes.

16. A dry powder inhaler according to claim 1, wherein the inhaler has an elongate body with a thin profile defining a pocket-sized inhaler that fits into the pocket of a garment worn by a user, wherein the floor of each blister comprises at least one thin piezoelectric polymer material layer with conductive selected portions in electrical communication therewith to define active energy releasing vibratory blister channels, and wherein, in operation, the blisters are adapted to be selectively activated to vibrate upon receipt of an electrical input.

17. A dry powder inhaler according to claim 1, wherein the blister package further comprises a substantially rigid spacer member disposed intermediate the projecting ceiling and the floor, the spacer having a plurality of spaced apart apertures, a respective aperture sized and configured to define sidewalls of a respective blister channel.

18. A dry powder inhaler according to claim 1, wherein the dry powder is a low-density dry powder.

19. A dry powder inhaler with a multi-dose dry powder package for dispensing pharmaceutical grade formulations of inhalable dry powder, comprising:

an inhaler housing;

a blister package held in the housing, the blister package comprising a plurality of spaced apart sealed blisters thereon, each blister having a projecting ceiling and a floor defining a blister channel therebetween, the blister channel comprising a dry powder therein;

a blister indexing mechanism in communication with the blister package to position a blister in a dispensing position;

a movable blade cartridge mounted in the housing configured to hold a blade at a forward portion thereof; and

an extendable mouthpiece attached to the movable blade cartridge, wherein, in operation, a user extends the mouthpiece outward and then retracts the mouthpiece inward to cause the blister package to advance thereby positioning a blister in the dispensing position in the inhaler, the retraction causing the blade cartridge to move the blade lengthwise across a blister ceiling held in the dispensing position in the inhaler to open the blister held in the dispensing position,

wherein the blisters have a perimeter shape, and wherein the blade is configured with a center aperture with a perimeter shape and size that substantially corresponds to that of a respective blister so that, when the blade and the blister are in a dispensing position, the blade defines a portion of an inspiratory exit flow path for the dry powder in the opened blister.

20. A dry powder inhaler according to claim 19, wherein, during active dispensing, the blade overlies an opened blister with the blade center aperture substantially aligned with the perimeter of the target blister.

21. A dry powder inhaler according to claim 20, wherein the ceiling has a first width, and wherein the blade has a second width that is less than the width of the ceiling.

22. A dry powder inhaler according to claim 21, wherein the blade has a substantially planar body with a beveled forward edge that travels substantially horizontally to open a respective blister.

23. A dry powder inhaler according to claim 22, wherein the beveled edge has a minor angle such that the blade forward edge rises less than about 30 degrees.

24. A dry powder inhaler with a multi-dose dry powder package for dispensing pharmaceutical grade formulations of inhalable dry powder, comprising:

an inhaler housing;

a blister package held in the housing, the blister package comprising a plurality of spaced apart sealed blisters thereon, each blister having a projecting ceiling and a floor defining a blister channel therebetween, the blister channel comprising a dry powder therein;

a blister indexing mechanism in communication with the blister package to position a blister in a dispensing position;

a movable blade cartridge mounted in the housing configured to hold a blade at a forward portion thereof;

an extendable mouthpiece attached to the movable blade cartridge, wherein, in operation, a user extends the mouthpiece outward and then retracts the mouthpiece inward to cause the blister package to advance thereby positioning a blister in the dispensing position in the inhaler, the retraction causing the blade cartridge to move the blade lengthwise across a blister ceiling held in the dispensing position in the inhaler to open the blister held in the dispensing position; and

an input signal generating circuit that is adapted to operatively serially engage each of the blisters, the input signal generating circuit configured to provide the electrical input to selectively flex a portion of a blister held in the dispensing location in the inhaler, responsive to the electrical input,

wherein the inhaler has an elongate body with a thin profile defining a pocket-sized inhaler that fits into the pocket of a garment worn by a user, wherein the floor of each blister comprises at least one thin piezoelectric polymer material layer with conductive selected portions in electrical communication therewith to define active energy releasing vibratory blister channels, and wherein, in operation, the blisters are adapted to be selectively activated to vibrate upon receipt of an electrical input.

25. A dry powder inhaler according to claim 24, wherein, in operation, the electrical input is configured to flex a blister in the dispensing position by applying a non-linear vibration input signal thereto, and wherein the non-linear input signal is selected to represent a priori flow characteristic frequencies of the dry powder formulation held in the blister channel.

26. A dry powder inhaler according to claim 25, wherein the non-linear vibration input signal comprises a plurality of different selected frequencies that correspond to the flow characteristic frequencies of the dry powder formulation held in the package.

27. A dry powder inhaler according to claim 25, wherein the non-linear vibration input signal is formed by the superposition of the plurality of different selected frequencies.

28. A dry powder inhaler according to claim 27, wherein the input generating circuit is configured to flex the channels by applying an amplitude modulated frequency selected to represent a priori flow characteristic frequencies of the dry powder formulation held in the package.

29. A dry powder inhaler according to claim 25, wherein the non-linear input signal is a low energy input signal having a plurality of superpositioned modulating frequencies, and wherein the non-linear input signal comprises frequencies in the range of between about 10 Hz to 1000 kHz.

30. A dry powder inhaler according to claim 29, wherein the non-linear input signal comprises carrier frequencies in the range of between about 15 kHz to 50 kHz.

31. A method of dispensing dry powder from an inhaler, comprising:

extending a mouthpiece of an inhaler outward to automatically index a blister on a blister package into a dispensing position;

vibrating the indexed blister; and

retracting the mouthpiece inward to open the indexed blister, wherein the retracting step comprises automatically advancing a cutting blade across a portion of a projecting ceiling of the indexed blister in the inhaler responsive to the retraction.

32. A method according to claim 31, further comprising moving the cutting blade in concert with the mouthpiece to open the projecting ceiling of the indexed blister responsive to the retracting step, wherein the blister package is circular.

33. A method according to claim 31, wherein the opening step comprises plowing across the ceiling with a member having a three-dimensional forward edge portion to substantially concurrently open and fold ceiling material as the blade travels across the blister.

34. A method according to claim 31, wherein the opening step comprises slicing a top horizontal portion of the blister ceiling as the blade moves across the ceiling in a direction that is generally aligned with a center axis extending in a length direction of an underlying blister channel.

35. A method according to claim 31, further comprising ceasing a forward movement of the cutting blade as the blade travels across a length of the ceiling before a forwardmost portion of the cutting blade reaches an innermost portion of the blister ceiling.

36. A method according to claim 35, wherein the cutting blade is configured to cut an opening in the blister ceiling that is less than the width of the ceiling.

37. A method according to claim 31, wherein the opening step comprises advancing a forwardmost portion of the cutting blade over an entire length of the ceiling so that a leading edge of the cutting blade resides outside a boundary of the opened blister.

38. A method according to claim 31, the method further comprising releasing dry powder in the opened blister to a user upon inspiration, wherein the inhaler blisters comprise a piezoelectric polymer, wherein the vibrating step comprises concurrently oscillating the piezoelectric polymer material, opening the blister;

and wherein the inspiratory step comprises releasing inhalable dry powder aerosol to the user while the piezoelectric polymer is vibrating upon inspiration.

39. A method according to claim 38, wherein the vibrating step comprises oscillating the indexed blister to impart energy to dry powder held in a respective indexed blister cavity to cause the dry powder to vibrate at a desired amplitude modified frequency to facilitate delivery of an inhalable dry powder aerosol.

40. A method according to claim 39, wherein the oscillating step causes the dry powder to vibrate with a non-linear motion to facilitate delivery of an inhalable dry powder aerosol.

41. A method according to claim 40, wherein the oscillating step comprises a frequency that is between about 10-200 Hz.

42. A method according to claim 40, wherein the non-linear motion comprises a non-linear input signal at a low energy having a plurality of superpositioned modulating frequencies.

43. A method of dispensing dry powder from an inhaler, comprising:

extending a mouthpiece of an inhaler outward to automatically index a blister on a blister package into a dispensing position;

vibrating the indexed blister;

retracting the mouthpiece inward to open the indexed blister; and

moving a cutting blade in concert with the mouthpiece to open a projecting ceiling of the indexed blister responsive to the retracting step;

wherein the extending step comprises rotating a gear attached to the blister package to index the blister in a dispensing position.

44. A method according to claim 43, further comprising:

contacting the gear with a pawl to urge the gear in a first rotative direction toward the dispensing position during the extending step; and

then

automatically locking the gear to inhibit the gear from rotating in the reverse rotative direction during the retracting step.

45. A method of dispensing dry powder from an inhaler, comprising:

extending a mouthpiece of an inhaler outward to automatically index a blister on a blister package into a dispensing position;

vibrating the indexed blister; and

retracting the mouthpiece inward to open the indexed blister,

wherein the retracting step comprises automatically advancing a cutting blade across a portion of a projecting ceiling of the indexed blister in the inhaler responsive to the retraction,

wherein the cutting blade comprises an aperture, and wherein the inhaler comprises a frame member with a gear and the blister package mounted to the frame member, the frame member having apertures that overlie and generally follow the perimeter shape of the blisters so that the blister projecting ceilings rise through respective frame apertures, the method further comprising aligning the cutting blade aperture to a respective one of the frame apertures over the indexed blister.

46. A method according to claim 45, further comprising forming a portion of an inspiratory exit flow path for the dry powder held in the opened blister using the aligned blade aperture over a respective frame aperture and the opened blister.

47. A method according to claim 45, wherein the the blister package is circular.

48. A blister packaging opening mechanism adapted for use in an inhaler, comprising:

a translatable cutting cartridge having a body with an enclosed airflow channel therein and an airflow entry port defining an inspiratory exit flowpath, the cutting cartridge further comprising a cutting blade residing on a lower portion of the cutting cartridge with an aperture sized and configured to reside about a perimeter of an opened blister, the cutting blade aperture is configured to allow powder to flow up therethrough and into the cutting cartridge channel and wherein, the cutting cartridge is configured to mount to an inhaler and move forward in the inhaler to cause the cutting blade to slice lengthwise across a projecting ceiling portion of an aligned blister sealing a blister channel, traveling generally parallel to a plane drawn over an upper portion of the underlying blister channel, to open the blister for dispensing a dry powder medicament held therein.

49. A blister packaging opening mechanism for use in an inhaler, comprising:

a translatable cutting cartridge having a forward plow portion with a cutting blade having an aperture that resides attached to a bottom portion of the forward plow portion, wherein the forward plow portion has an outer wall with an enclosed airflow channel therein and an airflow entry port defining an inspiratory exit flowpath, wherein, the cutting cartridge is configured to mount to an inhaler and move forward in the inhaler along a length direction of the blister to open and then fold at least one loose edge portion of a projecting ceiling of an aligned blister as the cutting cartridge advances to thereby open the blister for dispensing a dry powder medicament held therein, and wherein the cutting blade aperture resides over an opened blister and the powder from the opened blister flows therethrough and into the forward plow portion to then flowably exit the inhaler using the inspiratory exit flow path.

50. A blister packaging opening mechanism according to claim 49, the cutting blade has an elongate aperture, and wherein the airflow entry port resides above and upstream of the cutting blade.

51. A blister packaging opening mechanism according to claim 50, wherein the cutting blade aperture is sized and configured to snugly abut a perimeter of a respective blister.

52. A method for opening a sealed blister on a blister package, comprising:

advancing a plow mechanism across a sealed blister to open a projecting ceiling layer thereof to automatically lift and fold a loose edge portion of the opened ceiling layer, wherein the plow mechanism comprises a slicing blade with an aperture therein positioned at a bottom forwardmost portion thereof, and wherein the slicing step is carried out automatically in response to the advancing step;

slicing the sealed blister open and then using the plow mechanism to lift and fold the loose edge portion; and

maintaining the plow mechanism in an advanced position so that the slicing blade aperture resides over a perimeter of the opened blister and a portion of the plow resides thereabove to define an enclosed portion of an exit airflow path for powder in the opened blister.