Low cost electrodes for an iontophoretic device

• US 6,584,349 B1
• Filed: 11/17/1997
• Issued: 06/24/2003
• Est. Priority Date: 09/29/1995
• Status: Expired due to Fees

• Current Assignee: Vyteris, Inc.
• Original Assignee: Vyteris, Inc.
• Inventors: Haynes, John L., Sage, Burton H. Jr., Reddy, Vilambi, Bock, C. Randolph, DeNuzzio, John R.
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/971,458
• Time in Patent Office: 2,045 Days
• Field of Search: 604/20-21, 604/501, 607/115, 128/639
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir

Abstract

The present invention claims an apparatus for transdermal delivery of medicaments, with novel electrode systems, which avoids burns caused by changes in pH or excessive current applied at the sight of delivery, which is low in cost and easy to manufacture. In the present invention, preferably, the anode of the electrode system is predominantly formed from a low-cost bulk base metal which includes a coating of a precious metal thereon. The cathode of the electrode system is preferably formed from an chemically inert material which is a poor electron condutor and is coated on a good electron conductive material which has poor chemical stability. The electrode system of the present invention is highly efficient, easy to manufacture and cost-effective.

Claims

1. An anode electrode for an iontophoretic device useful for delivering a medicament comprising:

an electrode compartment, said electrode compartment including an electrolyte comprising a medicament and an anode electrode in electrical communication with said electrolyte, said anode electrode including;

at least two electrochemically active, dissimilar metals such that a first chemically inert metal provides a coating having a thickness of about 0.1 mil over a second metal, said chemically inert first metal substantially preventing a chemical reaction of said second metal with said electrolyte containing said medicament during shelf storage and a skin contacting compartment which is in ionic communication with said electrode compartment; and

an ion exchange material selected to capture positive ions of said second metal liberated by an electrochemical reaction during a use of said iontophoretic device to deliver said medicament, wherein said chemically inert first metal is substantially removed during said electrochemical reaction during an initial use of said device, said second metal thereby serving as the active electrode during subsequent delivery of said medicament.

2. An anode electrode as defined in claim 1, where the first metal comprises a precious metal and the second metal comprises a base metal wherein the anode electrode is fabricated from the base metal selected from the group consisting of iron, aluminum, tin, copper, zinc, nickel, brass, metal alloys and mixtures thereof, and wherein said precious metal coating serves to prevent said base metal from reacting with said electrolyte when said anode electrode is in electrical communication with said electrolyte and not in use, thereby prolonging the shelf-life of the anode electrode.

3. An anode electrode as defined in claim 2, wherein the anode electrode is in a form selected from the group consisting of:

printed ink on polymeric film, mesh, laminate and foil.

4. An anode electrode as defined in claim 1 wherein the second metal is expanded copper foil mesh and the first metal is silver.

5. A cathode electrode disosed in an electrode compartment comprising an ion exchange material, said cathode electrode comprising a first chemically inert electron conductor material coated to a thickness of about 0.1 mil over a second electron conductive material and wherein said chemically inert electron conductor first material is present in a sufficient quantity to inhibit interaction between an electrolyte present in said electrode compartment during shelf storage and said cathode electrode, and wherein said first material is substantially removed when an electrical potential sufficient to induce an iontophoretic current is applied to said cathode electrode thereby exposing said second material for electrochemical activity wherein said chemically inert electron conductive first material is selected from the group consisting of carbon, silver, platinum and gold.

6. A cathode of claim 5 wherein said electron conductive second material is selected from the group consisting of silver, copper, aluminum, zinc, iron, gold, platinum, conductive polymers, conductive ceramics and conductive adhesives and is different from said chemically inert first electron conductive material.

7. A cathode electrode of claim 6 wherein said electron conductive material is selected from the group consisting of printed ink on polymeric film, mesh, laminate and foil.

8. An iontophoretic device useful for delivery of a drug comprises:

an anode electrode having an electrode compartment, said electrode compartment including an electrolyte comprising a medicament and an anode electrode in electrical communication with said electrolyte, said anode electrode including at least two electrochemically active, dissimilar metals such that a first chemically inert metal disposed as a coating having a thickness of about 0.1 mil over a second metal, said chemically inert first metal substantially preventing a chemical reaction of said second metal with said electrolyte during shelf storage and a skin contacting compartment which is in ionic communication with said electrode compartment including an ion exchange material selected to capture positive ions of said second metal liberated by an electrochemical reaction during a use of said iontophoretic device to deliver said medicament, wherein said chemically inert first metal is substantially removed during said electrochemical reaction during initial use of said device, said second metal thereby serving as the active electrode during subsequent delivery of said medicament;

a cathode patch having a electrode compartment, said cathode electrode compartment including an electrolyte and a cathode electrode comprising chemically inert electron conductive first material coated on an electron conductive second material, different from said first material, said electrolyte including an ionizable reducible metal salt capable of being reduced at said cathode electrode and a cathode skin contacting compartment, the skin contacting compartment including an electrolyte for ionically contacting the skin of the patient, the skin compartment being ionically connected to said cathode electrode compartment and wherein said cathode electrode compartment further includes an ion selective material for substantially preventing ions of said reducible metal salt from migration into said cathode skin contacting compartment;

a power source electrically connected to said anode patch and said cathode patch so that when said anode patch and said cathode patch are disposed on the skin of a patient thereby forming a complete circuit capable of supporting an iontophoretic current between said patches through said patient'"'"'s skin so that when at least one of said cathode patch and said anode patch further includes a suitable medicament, said medicament is delivered into the skin of the patient.

9. A method for substantially preventing a destructive interaction during shelf storage between an electrolyte comprising a medicament and an electrode in an iontophoretic drug delivery device useful for delivering the medicament comprising:

providing an electrode having an electrode compartment;

providing an electrolyte comprising a medicament;

placing said electrolyte comprising said medicament in said electrode compartment;

providing a skin contacting compartment in ionic communication with said electrode compartment;

forming an electrode from a first electrochemically active metal capable of forming metallic ions in an electrochemical reaction;

selecting an ion exchange material capable of binding said metallic ions formed from said first electrochemically active metal;

placing said ion exchange material in one of said skin contacting compartment and said electrode compartment;

selecting another electrochemically active metal, different from said first metal and substantially inert when in contact with said electrolyte comprising said medicament;

applying said second electrochemically active metal as a coating having a thickness about 0.1 mil, over said electrode formed from said first electrochemically active metal; and

placing said electrode having said coating thereon in said electrode compartment in electrical communication with said electrolyte comprising said medicament, thereby providing said electrode having said chemically inert first metal substantially for substantially preventing a chemical reaction of said second metal with said electrolyte comprising said medicament during shelf storage of said device, said chemically inert first metal being substantially removed during an electrochemical reaction during an initial use of said device, said second metal thereby serving as the active electrode during subsequent delivery of said medicament.

10. An anode electrode for an iontophoretic medicament delivery device comprising:

an electrode compartment including an electrolyte comprising a medicament and an anode electrode in electrical communication with said electrolyte, said anode electrode including copper having an outside surface, said surface having a coating with a thickness of about 0.1 mil of silver thereon, said silver substantially preventing a chemical reaction between said copper and said electrolyte containing said medicament during shelf storage;

a skin contacting compartment which is in ionic communication with said electrode compartment; and

an ion exchange material selected to capture positive ions of said copper liberated by an electrochemical reaction during a use of said iontophoretic device to deliver said medicament, wherein said chemically inert first metal is substantially removed during said electrochemical reaction during an initial use of said device, said copper thereby serving as the active electrode during subsequent iontophoretic delivery of said medicament.

11. A cathode electrode for an iontophoretic delivery device comprising:

an electrode compartment including an electrolyte and a cathode electrode comprising carbon coated on silver, said electrolyte including an ionizable reducible metal salt capable of being reduced at said cathode electrode; and

a skin contacting compartment, the skin contacting compartment including an electrolyte for ionically contacting the skin of the patient, the skin compartment being ionically connected to said electrode compartment and wherein said electrode compartment further includes an ion selective material for substantially preventing ions of said reducible metal salt from migration into said skin contacting compartment.

12. An iontophoretic drug delivery device comprising:

an anode electrode comprising an electrode compartment including an electrolyte comprising a medicament and an anode electrode in electrical communication with said electrolyte, said anode electrode including copper having an outside surface, said surface having a coating with a thickness of about 0.1 mil of silver thereon, said silver substantially preventing a chemical reaction between said copper and said electrolyte containing said medicament during shelf storage;

a skin contacting compartment in ionic communication with said electrode compartment;

an ion exchange material selected to capture positive ions of said copper liberated by an electrochemical reaction during a use of said iontophoretic device to deliver said medicament, wherein said chemically inert first metal is substantially removed during said electrochemical reaction during an initial use of said device, said copper thereby serving as the active electrode during subsequent iontophoretic delivery of said medicament;

a cathode electrode comprising an electrode compartment including an electrolyte and a cathode electrode comprising carbon coated on silver, said electrolyte including an ionizable reducible metal salt capable of being reduced at said cathode electrode;

a skin contacting compartment, the skin contacting compartment including an electrolyte for ionically contacting the skin of the patient, the skin compartment being ionically connected to said electrode compartment and wherein said electrode compartment further includes an ion selective material for substantially preventing ions of said reducible metal salt from migration into said skin contacting compartment; and

a suitable power source connected to said anode electrode and said cathode electrode so that when said anode electrode and said cathode electrode are placed in ionic contact with the skin of a patient, a completed electrical circuit is established between said anode and said cathode so that said medicament is transported from said anode into said patient'"'"'s skin.

13. An anode patch for an electrode assembly of an iontophoretic medicament delivery device, the device delivering the medicament over a time period, the patch comprising:

an electrode compartment, said electrode compartment comprising an electrolyte and an electrode which is in ionic communication with said electrolyte, said electrode comprising at least two dissimilar electrochemically active metals such that a first metal is a coating over a second metal, wherein said first metal substantially prevents a chemical reaction of said second metal with said electrolyte during storage, and wherein said first metal is substantially removed by an electrochemical reaction within about a first 10% of the time period during an initial use of said patch such that said second metal serves as the active electrode; and

a skin contact compartment, said skin contact compartment in ionic communication with said electrode compartment.

14. The anode patch of claim 13 wherein said electrode is solid and substantially planar.

15. The anode patch of claim 13 wherein said electrode is selected from the group consisting of a foil, a laminate, and printed ink on polymeric film.

16. The anode patch of claim 13 wherein said electrode is an open mesh.

17. The anode patch of claim 16 wherein said open mesh is selected from the group consisting of woven, nonwoven screen, and expanded foil.

18. The anode patch of claim 13 wherein said electrode is formed by printed ink technology utilizing at least one technique selected from the group consisting of impression, lithography, offset, gravure, jet application, silk-screening, electroplating, and vacuum sputtering.

19. The anode patch of claim 13 wherein said skin contact compartment contains a medicament.

20. The anode patch of claim 13 further comprising a housing positioned on a surface of said electrode compartment.

21. The anode patch of claim 20 wherein said housing is made of a material selected from the group consisting of polymeric foam, plastic, polyvinyl chloride, and polyethylene.

22. The anode patch of claim 20 further comprising a backing film positioned on at least a part of said housing.

23. The anode patch of claim 13 further comprising a release liner positioned on an underside surface of said skin contact compartment.

24. The anode patch of claim 13 wherein said second metal is selected from the group consisting of a non-precious metal and an electrically conductive metal composite.

25. The anode patch of claim 24 wherein said second metal is selected from the group consisting of aluminum, tin, zinc, copper, nickel, brass, iron, silver, and alloys of any of aluminum, tin, zinc, copper, nickel, brass, iron, and silver.

26. The anode patch of claim 13 wherein said first metal is selected from the group consisting of a precious metal and a chemically inert metal.

27. The anode patch of claim 26 wherein said first metal is silver.

28. The anode patch of claim 13 further comprising an ion regulating material in ionic communication with said electrolyte and said electrode.

29. The anode patch of claim 28 wherein said ion regulating material is between said electrode and said skin contact compartment.

30. The anode patch of claim 29 wherein said ion regulating material is an anion exchange material.

31. The anode patch of claim 13 wherein said electrolyte comprises a hydrogel matrix including saline.

32. The anode patch of claim 31 further comprising an ion regulating material distributed in said matrix.

33. The anode patch of claim 32 wherein said ion regulating material is a cation exchange material.

34. The anode patch of claim 13 further comprising a compartment separation material between said electrode compartment and said skin contact compartment.

35. The anode patch of claim 34 wherein said compartment separation material is a size exclusion membrane.

36. The anode patch of claim 13 wherein said skin contact compartment includes a material selected from the group consisting of a solid material, a semi-solid material, a polymeric film, a semi-permeable membrane, a differentially permeable membrane, a hydrogel, and a microporous membrane.

37. The anode patch of claim 13, wherein said skin contact compartment includes agarose.

38. The anode patch of claim 13 wherein said first metal is silver and said second metal is copper.

39. The anode patch of claim 13 wherein said electrode includes an expanded copper foil mesh.

40. An iontophoretic device useful for iontophoretically delivering a medicament comprising:

the anode patch of claim 13; and

a cathode patch.

41. A cathode patch for an electrode assembly of an iontophoretic medicament delivery device, the patch comprising:

an electrode compartment, said electrode compartment comprising an electrolyte and an electrode in ionic communication with said electrolyte, said electrode comprising at least two materials such that a first material is a coating over a second material, said first material being carbon and said second material being selected from the group consisting of copper, silver, and aluminum, wherein said first material substantially prevents a chemical reaction of said second material with said electrolyte during storage, and wherein, during use, said materials are not consumed, and said electrode serves as an active electrode; and

a skin contact compartment, said skin contact compartment in ionic communication with said electrode compartment.

42. The cathode patch of claim 41 further comprising a compartment separation material between said electrode compartment and said skin contact compartment.

43. The cathode patch of claim 41 wherein said electrode is in solid substantially planar form.

44. The cathode patch of claim 41 wherein said electrode is selected from the group consisting of printed ink on polymeric film, a foil, and a laminate.

45. The cathode patch of claim 41 wherein said electrode is an open mesh.

46. The cathode patch of claim 45 wherein said open mesh is selected from the group consisting of woven, nonwoven screen, and expanded foil.

47. The cathode patch of claim 41 wherein said electrode is formed by printed ink technology utilizing at least one technique selected from the group consisting of impression, lithography, offset, gravure, jet application, silk-screening, electroplating, and vacuum sputtering.

48. The cathode patch of claim 41 wherein said skin contact compartment contains a medicament.

49. The cathode patch of claim 41 further comprising a housing positioned on a surface of said electrode compartment.

50. The cathode patch of claim 49 wherein said housing is made of a material selected from the group consisting of polymeric foam, plastic, polyvinyl chloride, and polyethylene.

51. The cathode patch of claim 41 further comprising a backing film positioned on at least a part of said housing.

52. The cathode patch of claim 41 further comprising a release liner positioned on an underside surface of said skin contact compartment.

53. The cathode patch of claim 41 wherein said second material is capable of conducting electrons.

54. The cathode patch of claim 41 wherein said first material is chemically inert and capable of conducting electrons.

55. The cathode patch of claim 41 wherein said electrolyte comprises a soluble, ionizable, reducible metal salt.

56. The cathode patch of claim 55 wherein said salt is selected from the group consisting of copper chloride, copper nitrate, copper sulfate, silver nitrate, zinc chloride, zinc nitrate, zinc sulfate, iron chloride, iron nitrate, and iron sulfate.

57. The cathode patch of claim 41 further comprising an ion regulating material in ionic communication with said electrolyte and said electrode.

58. The cathode patch of claim 57 wherein said ion regulating material is between said electrode compartment and said skin contact compartment.

59. The cathode patch of claim 58 wherein said ion regulating material is selected from the group consisting of an anion exchange membrane and anion exchange beads.

60. The cathode patch of claim 41 wherein said patch is fabricated on a thin flexible polymeric film.

61. The cathode patch of claim 41 wherein said patch comprises an expanded copper foil mesh.

62. The cathode patch of claim 41 wherein said first material is carbon and said second material is silver.

63. The cathode patch of claim 62 wherein said electrolyte of said patch is selected from the group consisting of a ZnCl₂ solution, a ZnSO₄ solution, a CuCl₂ solution, and a CuSO₄ solution.

64. An iontophoretic device useful for iontophoretically delivering a medicament comprising:

an anode patch; and

the cathode patch of claim 41.

65. An iontophoretic device useful for iontophoretically delivering a medicament, the device delivering the medicament over a time period, comprising:

an anode patch comprising

a first electrode compartment, said first electrode compartment comprising a first electrolyte and a first electrode in ionic communication with said first electrolyte, said first electrode comprising at least two dissimilar electrochemically active metals such that a first metal is a coating over a second metal, wherein said first metal substantially prevents a chemical reaction of said second metal with said first electrolyte during storage, and wherein said first metal is substantially removed by an electrochemical reaction within about a first 10% of the time period during an initial use of said patch such that said second metal serves as an active electrode, and

a first skin contact compartment, said first skin contact compartment in ionic communication with said first electrode compartment;

a cathode patch comprising

a second electrode compartment, said second electrode compartment comprising a second electrolyte and a second electrode in ionic communication with said second electrolyte, said second electrode comprising at least two materials such that a first material is a coating over a second material, wherein said first material substantially prevents a chemical reaction of said second material with said second electrolyte during storage, and wherein, during use, said materials are not consumed, and said electrode serves as an active electrode; and

a second skin contact compartment, said second skin contact compartment in ionic communication with said second electrode compartment; and

a power source electrically connected to said anode patch and said cathode patch.

66. The iontophoretic device of claim 65 further comprising a medicament.

67. The iontophoretic device of claim 66 wherein said medicament is located in said first skin contact compartment.

68. The iontophoretic device of claim 67 wherein said medicament has a positive charge in solution.

69. The iontophoretic device of claim 66 wherein said medicament is located in said second skin contact compartment.

70. The iontophoretic device of claim 69 wherein said medicament has a negative charge in solution.

71. The iontophoretic device of claim 65 wherein, in use, said anode patch and said cathode patch are disposed on the skin of a patient, thereby forming a complete circuit capable of supporting an iontophoretic current between said anode patch and said cathode patch through said skin so that said medicament is delivered into said skin.

72. The iontophoretic device of claim 71 wherein said anode patch and said cathode patch form a galvanic couple.

73. An anode patch for an electrode assembly of an iontophoretic medicament delivery device, the device delivering the medicament over a time period, the patch comprising:

an electrode compartment, said electrode compartment comprising an electrolyte and an electrode which is in ionic communication with said electrolyte, said electrode comprising at least two dissimilar electrochemically active metals such that a first metal is a coating over a second metal, wherein said first metal substantially prevents a chemical reaction of said second metal with said electrolyte during storage, and wherein said first metal is substantially removed by an electrochemical reaction within about a first 10% of the time period during an initial use of said patch such that said second metal serves as the active electrode; and

a skin contact compartment, said skin contact compartment in ionic communication with said electrode compartment.

74. The iontophoretic device of claim 73, wherein said skin contact compartment further comprises a drug.

75. An iontophoretic device useful for iontophoretically delivering a medicament over a time period, comprising:

an anode patch comprising

a first electrode compartment, said first electrode compartment comprising a first electrolyte and a first electrode in ionic communication with said first electrolyte, said first electrode comprising at least two dissimilar electrochemically active metals such that a first metal is a coating over a second metal, wherein said first metal substantially prevents a chemical reaction of said second metal with said first electrolyte during storage, and wherein said first metal is substantially removed by an electrochemical reaction within about a first 10% of the time period during an initial use of said patch such that said second metal serves as an active electrode, and

a first skin contact compartment, said first skin contact compartment in ionic communication with said first electrode compartment;

a cathode patch comprising

a second electrode compartment, said second electrode compartment comprising a second electrolyte and a second electrode in ionic communication with said second electrolyte, said second electrode comprising at least two materials such that a first material is a coating over a second material, wherein said first material substantially prevents a chemical reaction of said second material with said second electrolyte during storage, and wherein, during use, said materials are not consumed, and said electrode serves as an active electrode; and

a second skin contact compartment, said second skin contact compartment in ionic communication with said second electrode compartment; and

a power source electrically connected to said anode patch and said cathode patch.

76. The iontophoretic device of claim 75, wherein said first skin contact compartment further comprises a drug.

77. The iontophoretic device of claim 75, wherein said second skin contact compartment further comprises a drug.