Blister packages with frames and associated methods of fabricating dry powder drug containment systems

• US 20050109659A1
• Filed: 10/21/2004
• Published: 05/26/2005
• Est. Priority Date: 10/27/2003
• Status: Active Grant

• 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
• Granted Patent: US 7,377,277 B2
• Time in Patent Office: Days
• US Class Current: 206/538
• CPC Class Codes: A61M 15/001 using ultrasonic 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 2202/064 Powder
• CPC Class Codes: B65D 75/327 and forming several compartments
• CPC Class Codes: B65D 83/06 for dispensing powdered or granular material B65D83/04 takes precedence

Abstract

Dry powder blister packages include sealed blisters with a piezoelectric active layer that flexes to vibrate the dry powder in a blister to facilitate active dispersion.

Claims

1. A multi-dose blister package adapted for use in an inhaler, comprising:

a frame member having a plurality of spaced apart apertures;

a ceiling having a corresponding plurality of spaced apart projections, the ceiling disposed under the frame member and oriented relative to the frame member so that a respective ceiling projection extends through and rises above a respective frame aperture; and

a flexible floor underlying and attached to the ceiling, wherein the ceiling and floor are configured to define a plurality of spaced apart sealed blisters therebetween.

2. A multi-dose blister package according to claim 1, wherein the frame member is configured to resist flexure, and wherein the floor comprises a flexible piezoelectric material.

3. A multi-dose blister package according to claim 1, wherein the frame member has a substantially planar body, and wherein the frame member has sufficient rigidity to remain substantially planar during operation, wherein the ceiling is a substantially continuous layer that is sized and configured to extend over all of the blisters under the frame member with the projections aligned to reside in the frame member apertures.

4. A multi-dose blister package according to claim 1, wherein the floor comprises substantially laminated first and second flexible layers, with at least one of the first and second layers comprising a piezoelectric polymer material, and wherein, in operation, the piezoelectric material underlying a target blister is configured to repeatedly flex generally upward and downward upon receipt of an electrical input.

5. A multi-dose blister package according to claim 1, further comprising a bolus quantity of dry powder disposed in respective blisters.

6. A multi-dose blister package according to claim 1, wherein the floor comprises first and second flexible layers of different materials, a selected one of the layers comprising a piezoelectric polymer.

7. A multi-dose blister package according to claim 6, wherein the floor second layer comprises the piezoelectric polymer material and is attached to a bottom of the floor first layer, the floor second layer further comprising a predetermined conductive pattern disposed over a first primary surface and a conductive material disposed over at least a portion of an opposing second primary surface.

8. A multi-dose blister package according to claim 7, wherein the conductive material on the second primary surface of the second layer comprises a metallized coating disposed to cover substantially all of the second primary surface.

9. A multi-dose blister package according to claim 7, wherein the predetermined conductive pattern on the second layer comprises a plurality of spaced apart conductive regions, each region sized and configured to be substantially coextensive with a bottom portion of a respective blister.

10. A multi-dose blister package according to claim 9, wherein the predetermined conductive pattern further comprises at least one signal trace extending away from each region.

11. A multi-dose blister package according to claim 10, wherein the signal trace for each blister travels toward a respective conductive contact zone on the first primary surface of the second layer.

12. A multi-dose blister package according to claim 1, wherein the ceiling, frame member, and first layer of the floor have a circular shape with substantially aligned center apertures that expose a portion of an upper surface of the second layer.

13. A multi-dose blister package according to claim 1, wherein neighboring pairs of sealed blisters comprise a different dry powder held therein.

14. A multi-dose blister package according to claim 13, wherein the neighboring blisters are sized and configured to, in operation and in position in an inhaler, release their dry powders in combination substantially concurrently to a user upon inhalation.

15. A multi-dose blister package according to claim 1, wherein the ceiling comprises foil.

16. A multi-dose blister package according to claim 7, wherein the first floor layer comprises foil.

17. A multi-dose blister package according to claim 16, wherein the second layer of the floor is defined by a PVDF film.

18. A multi-dose blister package according to claim 1, wherein the frame member comprises a molded polymer body.

19. A multi-dose blister package according to claim 7, wherein the second layer is a PVDF layer that has a surface area that is about the same as that of the first floor layer.

20. A multi-dose blister package according to claim 7, wherein the second layer is a PVDF layer that has a surface area that is less than that of the first floor layer.

21. A multi-dose blister package according to claim 20, wherein the second layer has a shape that generally corresponds to the shape of the predetermined conductive pattern.

22. A multi-dose blister package according to claim 1, wherein the frame member is a substantially flat circular shape with a center aperture and comprises a polymer material.

23. A multi-dose blister package according to claim 5, wherein the package is adapted to be releaseably inserted into an inhaler and disposable after the dry powder in the blisters has been depleted.

24. A multi-dose blister package according to claim 1, wherein the frame member is releaseably attached to the ceiling.

25. A multi-dose blister package according to claim 1, wherein the frame member is non-releasably attached to the ceiling.

26. A multi-dose blister package according to claim 1, wherein the ceiling is configured with a selected formable material having sufficient thickness and structural rigidity to be able to retain the projecting ceiling shapes.

27. A multi-dose blister package according to claim 1, wherein the blisters have a perimeter shape when viewed from the top, wherein the frame member apertures have substantially the same blister perimeter shape when viewed from the top, and wherein a respective frame member aperture surrounds a corresponding blister perimeter shape.

28. A multi-dose blister package according to claim 27, wherein the blister perimeter shape is substantially circular when viewed from the top.

29. A multi-dose blister package according to claim 27, wherein the blister has an elongate perimeter shape.

30. A multi-dose blister package according to claim 7, wherein, in operation, the piezoelectric polymer is electrically activated to vibrate a desired blister.

31. A multi-dose blister package according to claim 30, wherein the ceiling is a foil-containing ceiling having sufficient structural rigidity to be formed into and retain the ceiling projection shapes.

32. A multi-dose blister package according to claim 1, further comprising a power source and an input signal generating circuit that is configured to provide electrical input to selectively flex the floor of a target blister held in a dispensing location in the inhaler, responsive to the electrical input.

33. A multi-dose blister package according to claim 32, further comprising computer readable program code that is in communication with the input signal generating circuit and is configured with a predetermined non-linear vibration input signal selected to represent a priori flow characteristic frequencies of the dry powder formulation held in the blister.

34. A multi-dose blister package according to claim 5, wherein the dry powder is a low-density dry powder.

35. A multi-dose blister package according to claim 12, further comprising a rotatable gear having circumferentially spaced apart gear teeth, the gear disposed in the window of the aligned center apertures and mounted to the frame member so that the blister package rotates with the gear.

36. A multi-dose blister package according to claim 13, wherein selected neighboring blisters are configured closer together than other blisters.

37. A method for making a multi-dose blister package adapted for use in an inhaler, comprising:

providing a frame member having a plurality of spaced apart apertures;

forming a plurality of spaced apart wells in a ceiling that, in position on a sealed blister package, define projections;

positioning the ceiling above the frame and aligned therewith so that a respective ceiling well extends through and falls below a respective frame aperture;

positioning a quantity of dry powder in the ceiling wells; and

sealing a flexible floor to the ceiling to define a plurality of spaced apart sealed blisters therebetween.

38. A method according to claim 37, wherein the frame member is configured to resist flexure, and wherein the floor comprises a flexible piezoelectric material.

39. A method according to claim 37, wherein the frame member has a substantially planar body with sufficient rigidity to remain substantially planar during operation, wherein the ceiling is a substantially continuous layer that is sized and configured to extend over all of the blisters under the frame member, further comprising inverting the sealed blister package after the sealing step so that, in operative position, the frame member defines a top surface with the ceiling underlying the frame member with the ceiling projections extending above the frame member through the frame member apertures.

40. A method according to claim 37, wherein the floor comprises a piezoelectric polymer material.

41. A method according to claim 37, further comprising attaching first and second flexible floor layers, at least one of the first and second layers comprising a flexible piezoelectric material, the first and second floor layers configured, in operation, so that the piezoelectric material is configured to repeatedly flex generally upward and downward under a blister upon receipt of an electrical input.

42. A method according to claim 37, wherein the floor comprises first and second flexible layers of different materials, a selected one of the layers comprising a piezoelectric polymer.

43. A method according to claim 41, wherein the floor second layer comprises the piezoelectric material, the method further comprising forming a predetermined conductive pattern on a selected primary surface of the piezoelectric material before attaching the first and second floor layers together.

44. A method according to claim 43, further comprising metallizing the opposing primary surface of the second floor.

45. A method according to claim 43, wherein the predetermined conductive pattern on the second layer comprises a plurality of spaced apart conductive regions, each region sized and configured to be substantially coextensive with a bottom portion of a respective blister.

46. A method according to claim 45, wherein the predetermined conductive pattern is formed to comprise at least one signal trace extending away from each region.

47. A method according to claim 46, wherein the signal trace for each blister is formed to travel toward a respective conductive contact zone on the first primary surface of the second layer.

48. A method according to claim 47, wherein the signal trace for each blister is formed to extend toward a different contact zone.

49. A method according to claim 47, wherein selected pairs of blisters have traces that travel toward a common contact zone that is spatially separate from the other contact zones for the other blisters.

50. A method according to claim 41, wherein the ceiling, frame member, and first layer of the floor have a circular shape with center apertures, the method further comprising substantially aligning the center apertures to expose a portion of an upper surface of the second layer.

51. A method according to claim 37, further comprising forming selected neighboring pairs of sealed blisters to be closer together than other blisters, and wherein the positioning step comprises placing a different dry powder in the closer neighboring blisters.

52. A method according to claim 41, wherein the floor second layer comprises a piezoelectric polymer, wherein the sealing step comprises:

attaching the first floor layer to the ceiling to concurrently seal the blisters with the dry powder captured therein; and

then

attaching the second floor layer to the first floor layer.

53. A method according to claim 52, further comprising cutting the ceiling and first floor layer into a desired shape after the sealing step before the second floor layer is attached to the first floor layer.

54. A method according to claim 52, further comprising inverting the sealed blister package after the first attaching step so that, in operative position, the frame member defines a top surface with the ceiling underlying the frame member with the ceiling projections extending above the frame member through the frame member apertures.

55. A method according to claim 52, further comprising inverting the sealed blister package after the first and second attaching steps are complete so that, in operative position, the frame member defines a top surface with the ceiling underlying the frame member with the ceiling projections extending above the frame member through the frame member apertures.

56. A method according to claim 52, further comprising testing the second floor layer and/or blister package for electrical integrity of the piezoelectric material and/or predetermined conductive pattern.