Transdermal delivery device

• US 20050228340A1
• Filed: 03/24/2005
• Published: 10/13/2005
• Est. Priority Date: 03/24/2004
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Cleary, Gary W., Klemm, Steven R.
• Granted Patent: US 7,611,481 B2
• Time in Patent Office: Days
• US Class Current: 604/46
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

A dermal, transdermal, mucosal or transmucosal delivery device includes a backing layer overlying an ingredient containing reservoir, and having a microprotrusion array attached thereto, a cover for the reservoir having at least one opening therethrough, an adhesive layer and a liner layer. Upon removal of the liner layer, the device may be placed over the desired area of the skin or mucosa and adhesively applied thereto allowing the ingredients to flow from the reservoir through the at least one opening to the skin or mucosa.

Claims

1. An ingredient delivery device, comprising:

an ingredient-containing reservoir;

a backing layer overlying the ingredient-containing reservoir, a microprotrusion array having a plurality of microprotrusions; and

a release liner overlying the backing layer and the microprotrusion array.

2. The ingredient delivery device of claim 1, wherein the backing layer is from about ½

mil to about 5 mils thick.

3. The ingredient delivery device of claim 2, wherein the release liner film is from about 1 mil to about 10 mils thick.

4. The ingredient delivery device of claim 1, further including an adhesive layer disposed between the ingredient-containing reservoir and the backing layer film, the microprotrusion array being adhered to the backing layer film by the adhesive layer.

5. The ingredient delivery device of claim 1, wherein the microprotrusion array is comprised of a base layer with microprotrusions projecting from the base layer, wherein the base layer is from about 1 mil to about 10 mils thick and the microprotrusions are from about 20 to about 500 microns in length.

6. The ingredient delivery device of claim 5, wherein the base layer is from about 2 mils to about 8 mils thick and the microprotrusions are from about 50 to about 500 microns in length.

7. The ingredient delivery device of claim 6, wherein the base layer is from about 4 mils to about 6 mils thick and the microprotrusions are from about 100 to about 250 microns in length.

8. The ingredient delivery device of claim 5, wherein the release liner film includes an outer protective layer and at least an adhesive layer thereon, wherein the adhesive layer includes a gap in coverage which is approximately coextensive with the microprotrusion array to at least partially accommodate the thickness of the microprotrusion array between the backing layer and the outer protective layer.

9. The ingredient delivery device of claim 8, wherein the release liner film further includes a barrier layer adhered to the adhesive layer, and a release coating layer on the barrier layer, the barrier layer and the release coating layer including a gap generally corresponding in size to the gap in coverage of the adhesive layer.

10. The ingredient delivery device of claim 1, wherein the backing layer and the cover layer define a space therebetween, and the reservoir comprises the space between the backing layer film and a cover layer attached to the backing layer, wherein the cover layer covers at least one opening such that ingredients contained within the reservoir can pass from the reservoir.

11. The ingredient delivery device of claim 10, wherein the at least one opening comprises a plurality of micro pores.

12. The ingredient delivery device of claim 1, wherein the microprotrusion array is attached to the backing layer.

29. The device of claim 1, wherein the backing member overlies the ingredient containing reservoir, the backing member including a force gauge, wherein the force gauge includes an indicator which indicates when the microprotrusion layer has penetrated to a desired depth in a patient'"'"'s skin.

30. The device of claim 29 in which the adhesive layer overlies at least a portion of the cover.

31. The device of claim 30, wherein the liner is a release liner for the device, the release liner substantially covering the microprotrusion layer, the adhesive layer, the sealing surface, and the opening of the cover.

32. The device of claim 31, wherein the first and second seals are heat seals between the cover and the backing member and between the liner and the cover respectively.

33. The device of claim 31, wherein the liner is a composite member comprising:

an outer protective layer and a barrier layer having an exposed surface, the liner further including an adhesive coating between the outer protective layer and the barrier layer, and a release coating on the exposed surface of the barrier layer; and

wherein

the barrier layer has an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

34. The device of claim 33, wherein the adhesive layer is a composite member comprising:

a first adhesive coating, a second adhesive coating and a barrier layer therebetween; and

wherein

the barrier layer, including its first adhesive coating and its second adhesive coating, has an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

35. The device of claim 34, wherein the release coating of the liner is releasably adhered to at least a portion of the second adhesive coating of the adhesive layer.

51. The device of claim 1, wherein the reservoir includes first and second compartments that are sealed from one another.

52. The device of claim 1, including a pump operably connected to the reservoir for pressurizing the reservoir.

53. The device of claim 52, wherein the pump comprises a syringe.

54. The device of claim 52, wherein the pump is connected to the reservoir by a conduit and a releasable fitting.

55. The device of claim 52, wherein the pump is connected to the reservoir by a needle that extends through a resealing port including a film layer attached to the reservoir.

56. The device of claim 1, including a resilient member that tends to cause a recoil force pulling the microprotrusions away from and out of a patient'"'"'s skin.

57. The device of claim 56, wherein the resilient member comprises a layer of foam extending across at least a portion of the microprotrusion array.

58. The device of claim 56, wherein the resilient member has a ring-like shape and extends around a perimeter of the microprotrusion array.

59. The device of claim 1, wherein the microprotrusion array includes a plurality of openings therethrough.

60. The device of claim 1, including a bumper member adjacent the microprotrusion array, the bumper member having sufficient thickness to protect the microprotrusions from damage prior to use.

61. The device of claim 60, wherein the bumper member extends around at least a portion of the microprotrusion array.

62. The device of claim 61, wherein the bumper member has a ring-like shape and is made of a substantially incompressible material.

13. A microprotrusion transdermal delivery device, comprising:

an ingredient-containing reservoir defining a perimeter;

a backing member overlying an ingredient containing reservoir, said backing member being made of a material which is substantially impermeable to ingredients contained in the reservoir;

a cover for the reservoir, the cover being made of a material substantially impermeable to ingredients contained in the reservoir, but having at least one opening defining a perimeter, such that ingredients to be delivered from the reservoir will flow through the opening, but will not readily flow through the material of which the cover is made;

a first seal sealing the cover to the backing member at the perimeter of the reservoir wherein the first seal which is not subject to permeation, disintegration or degradation by any ingredient contained in the reservoir;

an adhesive layer adhered to the backing member for adhering the device to a patient'"'"'s skin or mucosa, the adhesive layer not extending to the perimeter of the opening in the cover, such that a portion of the cover surrounding the perimeter of the opening is exposed to thereby define a cover sealing surface;

a microprotrusion layer at least partially adhered to the adhesive layer, the microprotrusion layer including at least one opening therethrough generally aligned with the opening in the cover, such that ingredients to be delivered from the reservoir flow through the opening in the microprotrusion layer, wherein the microprotrusion layer pierces at least a portion of the skin or mucosa when the device is applied to a subject'"'"'s skin or mucosa;

a second seal;

a liner covering the sealing surface of the cover and the opening in the cover, the liner being releasably sealed to the sealing surface of the cover by a second seal, wherein the second seal is not subject to permeation, disintegration or degradation by any ingredient in the reservoir;

whereby ingredients contained in the reservoir are sealed therein during storage and non-use by the first and second seals, but are free to flow through the openings in the microprotrusion layer and the cover and onto a subject'"'"'s skin or mucosa when the liner is removed from the device and the device is applied to skin or mucosa.

14. The device of claim 13 in which the adhesive layer overlies at least a portion of the cover.

15. The device of claim 14, wherein the liner is a release liner for the device, the release liner covering the microprotrusion layer, the adhesive layer, the sealing surface, and the opening of the cover.

16. The device of claim 15, wherein the first and second seals comprise heat seals between the cover and the backing member and between the liner and the cover respectively.

17. The device of claim 15, wherein the liner is a composite member comprising:

an outer protective layer and a barrier layer and an adhesive coating therebetween, and wherein the barrier layer has an exposed surface with a release coating on the exposed surface; and

wherein

the barrier layer has an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

18. The device of claim 15, wherein the microprotrusion layer comprises a base layer having microprotrusions projecting therefrom.

19. The device of claim 18, wherein the microprotrusion layer includes a channeled surface in the base layer, adjacent to the adhesive layer to provide flow of the ingredients from the reservoir.

20. The device of claim 17, wherein the adhesive layer is a composite member comprising:

a first adhesive coating, a second adhesive coating and a barrier layer therebetween; and

wherein

the barrier layer has an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

21. The device of claim 20, wherein the second adhesive coating adjacent the microprotrusion layer comprises a pattern-coated adhesive.

22. The device of claim 20, wherein the release coating of the liner is releasably adhered to at least a portion of the second adhesive coating of the adhesive layer.

23. The device of claim 13, wherein the ingredients contained in the reservoir comprise a liquid.

24. The device of claim 13, wherein the reservoir comprises an absorbable material.

25. The device of claim 13, wherein the ingredients contained in the reservoir comprise a gel.

26. The device of claim 13, including a rate controlling membrane disposed between the cover and said reservoir.

27. The device of claim 13, including a rate controlling membrane disposed between the cover and the adhesive layer.

28. The device of claim 13, wherein the microprotrusion layer includes a channeled surface in the base layer, adjacent to the adhesive layer, to provide flow of ingredients from the reservoir.

36. A transdermal delivery device, comprising:

a reservoir containing ingredients and defining a perimeter;

a backing member overlying the reservoir, the backing member being made of a material which is substantially impermeable to the ingredients contained in the reservoir;

a cover for the reservoir, the cover being made of a material substantially impermeable to ingredients contained in the reservoir, but having at least one opening therein defining a perimeter, such that ingredients from the reservoir flow through the opening, but will not readily flow through the material of which the cover is made;

a first seal sealing the cover to the backing member at the perimeter of the reservoir, wherein the first seal which is not subject to permeation, disintegration or degradation by any ingredient contained in the reservoir;

an adhesive layer adhered to the backing member for adhering the device to a patient'"'"'s skin or mucosa, the adhesive layer not extending to the perimeter of the opening in the cover, such that a portion of the cover surrounding said perimeter of the opening is exposed to thereby define a cover sealing surface;

an ingredient containing material layer at least partially adhered to the adhesive layer, wherein the ingredient containing material does not extend to the perimeter of the opening;

a liner covering the sealing surface of the cover and the opening in the cover;

a second seal releasably sealing the liner to the sealing surface of the cover, wherein the second seal is not subject to permeation, disintegration or degradation by any ingredient in the reservoir;

whereby ingredients in the reservoir are sealed therein during storage and non-use by the first and second seals, the cover and liner, but are free to flow through the opening and onto a subject'"'"'s skin or mucosa when the liner is removed from the device and the device is applied to such skin or mucosa.

37. The device of claim 36, further including a microprotrusion layer at least partially adhered to the adhesive layer, the microprotrusion layer including at least one opening therethrough substantially aligned with the opening in the cover, such that ingredients from the reservoir may flow through the opening, and wherein the microprotrusion layer pierces at least a portion of the skin or mucosa when the device is applied to a subject'"'"'s skin or mucosa;

the opening in the ingredient containing material layer being sufficiently large that the microprotrusion layer is positioned within the opening in the ingredient containing material layer.

38. The device of claim 37, wherein the liner is a release liner for the device, the release liner covering the microprotrusion layer and the adhesive layer as well as the sealing surface and the opening of the cover.

39. The device of claim 38, wherein the first and second seals comprise heat seals between the cover and the backing member and between the liner and the cover respectively.

40. The device of claim 36, wherein the liner is a composite member comprising:

an outer protective layer and a barrier layer with an adhesive coating therebetween, the barrier layer defining an exposed surface, the outer protective layer further including a release coating on the exposed surface of the barrier layer; and

wherein

the barrier layer, including its adhesive coating and its release coating, has an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

41. The device of claim 40, wherein the release coating of the liner is releasably adhered to the second adhesive coating of the adhesive layer.

42. The device of claim 37, wherein a rate-controlling membrane is disposed between the cover and the reservoir.

43. The device of claim 37, wherein a rate controlling membrane is disposed between the cover and the adhesive layer.

44. A microprotrusion transdermal delivery device comprising:

an ingredient containing reservoir defining a perimeter;

a backing member overlying the reservoir, the backing member being made of a material which is substantially impermeable to ingredients contained in the reservoir;

a membrane covering the reservoir, the membrane being permeable by ingredients to be dispensed by the device;

a first seal sealing the membrane to the backing member at the perimeter of the reservoir by a first seal which is not subject to permeation, disintegration or degradation by any ingredient to be contained in the reservoir;

an adhesive layer adhered to the backing member for adhering the device to a patient'"'"'s skin or mucosa, the adhesive layer including an opening therein which is aligned with at least a portion of the membrane, such that a portion of the membrane is exposed to define a membrane sealing surface;

a microprotrusion layer at least partially adhered to the adhesive layer, the microprotrusion layer including at least one opening therethrough substantially aligned with the opening in said adhesive layer such that ingredients to be delivered from the reservoir through the membrane may flow through the opening in the adhesive layer and the opening in the microprotrusion layer, and wherein the microprotrusion layer pierces at least a portion of the skin or mucosa when the device is applied to a subject'"'"'s skin or mucosa;

a second seal which is not subject to permeation, disintegration or degradation by any ingredient contained in the reservoir;

a liner covering the sealing surface of the membrane, the liner being releasably sealed to the sealing surface of the membrane by the second seal;

ingredients contained in the reservoir are sealed therein during storage and nonuse by the first and second seals, and the liner, but are free to flow through the membrane and the opening and onto a subject'"'"'s skin or mucosa when the liner is removed from the device and the device is applied to such skin or mucosa.

45. The device of claim 44 wherein the adhesive layer extends at least partially over the membrane.

46. The device of claim 44 wherein the backing member includes a force gauge, the force gauge including an indicator which indicates when the microprotrusion layer has penetrated to a desired depth in a patient'"'"'s skin.

47. The device of claim 46, wherein the force gauge comprises a raised area of the backing member.

48. A transdermal delivery device comprising:

an ingredient containing reservoir;

a backing member overlying the reservoir, the backing member being made of a material which is substantially impermeable to ingredients contained in the reservoir;

a first seal which is not subject to permeation, disintegration or degradation by any ingredient to be contained in the reservoir;

a membrane made of a microporous material covering the reservoir, the membrane being sealed to the backing member at the perimeter of the reservoir by the first seal;

an adhesive layer adhered to the backing member for adhering the device to a patient'"'"'s skin or mucosa, the adhesive layer including an opening therein which is aligned with at least a portion of the membrane such that a portion of the membrane is exposed to define a membrane sealing surface;

an ingredient containing material layer at least partially adhered to the adhesive layer, the ingredient containing material layer including an opening aligned with the opening in the adhesive layer;

a second seal which is not subject to permeation, disintegration or degradation by any ingredient contained in the reservoir;

a liner covering said sealing surface of said membrane, the liner being releasably sealed to the sealing surface of the membrane by the second seal;

whereby ingredients contained in the reservoir are sealed therein during storage and nonuse by the first and second seals, and the liner, but are free to flow through the opening and onto a subject'"'"'s skin or mucosa when the liner is removed from the device and the device is applied to such skin or mucosa.

49. The device of claim 48, wherein the liner is a composite member comprising:

an outer protective layer and a barrier layer with an adhesive coating therebetween, and a release coating on an exposed surface of the barrier layer;

the barrier layer, including its adhesive coating and its release coating, having an opening therein which is sufficiently large to expose the opening and the sealing surface of the cover, whereby the outer protective layer is sealed directly to the sealing surface of the cover by the second seal.

50. The device of claim 49, wherein the microprotrusion layer comprises at least one microprotrusion, and wherein the microprotrusion layer is comprised of a synthetic material.

63. A method of making a transdermal delivery device, comprising:

providing a polymer film backing layer;

permanently deforming the polymer film to form a depression defining a perimeter;

providing a cover layer;

sealing the cover layer to the backing layer around the perimeter of the depression so that the depression forms a reservoir cavity;

at least partially filling the cavity with an active ingredient;

providing at least one opening through the cover layer to the reservoir cavity;

adhering a liner to at least a selected one of the backing layer and the cover with the liner covering the opening through the cover layer.

64. The method of claim 63, wherein:

the depression in the polymer film backing layer is made by thermoforming.

65. The method of claim 63, including providing a device for forming at least one opening in a layer of skin.

66. The method of claim 65, including securing the device to the transdermal delivery device proximate the cavity.

67. The method of claim 66, wherein the device comprises an array of microneedles that is adhered to the cover layer.