Transdermal drug delivery patch system, method of making same and method of using same

• US 20030225360A1
• Filed: 03/11/2003
• Published: 12/04/2003
• Est. Priority Date: 03/11/2002
• Status: Active Grant

• Current Assignee: ​Passport Technologies, Inc.
• Original Assignee: Altea Therapeutics Corporation (Nitto Denko Corporation)
• Inventors: Smith, Alan, McRae, Stuart, Eppstein, Jonathan
• Granted Patent: US 7,392,080 B2
• Time in Patent Office: Days
• US Class Current: 604/19
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/33 Controlling, regulating or measuring
• CPC Class Codes: A61M 2205/3303 Using a biosensor
• CPC Class Codes: A61M 2210/04 Skin
• CPC Class Codes: A61M 2230/20 Blood composition characteristics
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The invention provides for a transdermal drug delivery device for forming a drug delivery patch system comprising:

a) an actuator comprising:

i) an outer body defining a top of the actuator, the outer body containing a cavity;

ii) a controller board comprising driving electronics and a battery, the controller board being positioned within the cavity; and

iii) an interface connection port for receiving a porator array, the interface connection port containing an anode and a cathode;

b) the porator array comprising:

i) a top surface, with a removable adhesive attached to the top surface, the top surface containing two concentric electrical contact rings for contacting the interface connection port at the anode and the cathode upon removal of the adhesive layer;

ii) a bottom surface comprising a tissue interface membrane, the tissue interface membrane further comprising a substrate with at least one porator contained on or within the substrate, the bottom surface further comprising an adhesive layer for attaching the porator array to a tissue membrane; and

iii) an extension tab laterally and removably attached to the bottom surface, the extension tab including an adhesive applied on the bottom thereof, thereby allowing the extension tab to remain on the tissue membrane upon removal of the porator array; and

iv) a release liner removably attached to the bottom surface; and

c) a reservoir patch attached to the extension tab, the reservoir patch being applied to the microporated area of the tissue membrane after poration.

The invention also provides for methods of making and methods of using the same.

Claims

1. A drug delivery patch system comprising:

a) an actuator comprising;

i) an outer body defining a top of said actuator, said outer body containing a cavity;

ii) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

iii) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

b) said porator array comprising;

i) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

ii) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

iii) an extension tab laterally and removably attached to said bottom surface, said extension tab including an adhesive applied on the bottom thereof, thereby allowing said extension tab to remain on said tissue membrane upon removal of said porator array; and

iv) a release liner removably attached to said bottom surface; and

c) a reservoir patch attached to said extension tab, said reservoir patch being applied to said microporated area of said tissue membrane after poration.

2. The drug delivery patch system according to claim 1 wherein said reservoir patch further comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing a drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

3. The drug delivery patch system according to claim 2 wherein said reservoir patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane.

4. The drug delivery patch system according to claim 1 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

5. The drug delivery patch system according to claim 1 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

6. The drug delivery patch system according to claim 1 wherein said actuator further comprises a control button for initiating poration of said membrane.

7. An integrated monitoring and delivery system comprising:

a) a delivery and extraction patch comprising;

i) a first section comprising a first tissue interface layer and a first reservoir for storing a permeant composition to be applied to a tissue membrane, said first tissue interface membrane further comprising a substrate with a first porator array contained on or within said substrate;

ii) a second section comprising a second tissue interface layer and a second reservoir for collecting an analyte from said tissue membrane for analysis, said second tissue interface membrane further comprising a substrate with a second porator array contained on or within said substrate;

iii) an adhesive for adhering said patch to said tissue membrane;

b) a controller for actuating said porator array, thereby forming micropores in said tissue membrane; and

c) an apparatus for analyzing said analyte, said apparatus containing an algorithm to determine a concentration of said analyte and control delivery of said permeant composition based on said analyte concentration.

8. The integrated monitoring and delivery system according to claim 7 wherein said first and second porator arrays are the same porator array.

9. The integrated monitoring and delivery system according to claim 7 wherein said first and second porator arrays are different porator arrays.

10. The integrated monitoring and delivery system according to claim 7 wherein said first and second porator arrays are each selected from the group consisting of a probe element, an electromechanical actuator, a microlancet, an array of micro-needles or lancets, a thermal energy ablator, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer.

11. The integrated monitoring and delivery system according to claim 7, wherein said first and second reservoirs each further comprise:

a) a top layer;

b) a middle layer that has at least one cavity for storing a drug or other permeant composition to be applied to said membrane in said first reservoir, and for accepting said analyte in said second reservoir; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane in said first reservoir, and through which said analyte is extracted in said second reservoir.

12. The integrated monitoring and delivery system according to claim 7 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

13. The integrated monitoring and delivery system according to claim 7 wherein said first and second porator arrays are each selected from the group consisting of a wire conductor, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a shape memory alloy material and an etched conductive material.

14. A flux enhancement device comprising:

a) an outer wall defining a cell cavity, said outer wall having an edge which bounds said cell cavity and interfaces with a tissue membrane having a micropore, said cell cavity having an opening on at least one end, said opening interfacing with said tissue membrane;

b) a reservoir defining an inner cavity, said reservoir being contained within said cell cavity and having an opening oriented toward said opening in said cell cavity;

c) a first compliant membrane spanning a gap between said reservoir and said outer wall at said membrane interface end of said cell cavity; and

d) a second compliant membrane forming a pressure chamber defined by a wall of said reservoir, said outer wall and said first compliant membrane.

15. The flux enhancement device according to claim 14 wherein said outer wall is a hollow cylinder in a shape selected from the group consisting a circular cross-section and a polygonal cross-section.

16. The flux enhancement device according to claim 14 wherein said reservoir contains a permeant composition to be administered to said tissue membrane by way of said micropore.

17. The flux enhancement device according to claim 14 wherein said reservoir is adapted to receive an analyte extracted from said tissue membrane by way of said micropore.

18. The flux enhancement device according to claim 14 wherein said reservoir is removably contained within said cell cavity.

19. The flux enhancement device according to claim 14 wherein said reservoir is formed as an integral portion of said cell cavity.

20. The flux enhancement device according to claim 14 wherein said first compliant membrane includes an adhesive layer to promote sealing with said tissue membrane.

21. The flux enhancement device according to claim 14 wherein said edge of said outer wall and said opening of said reservoir include an adhesive layer to promote sealing with said tissue membrane.

22. The flux enhancement device according to claim 14 further comprising a first pressure port which modulates pressure in said cell cavity and a second pressure port which modulates pressure in said inner cavity.

23. The flux enhancement device according to claim 14 further comprising a controller for controlling delivery of a permeant composition to said tissue membrane or extraction of an analyte from said tissue membrane.

24. A method of delivering a drug to a patient in need thereof, comprising the steps of:

a) contacting a poration device to a tissue membrane of said patient, said a poration device comprising;

i) an outer body defining a top of said poration device, said outer body containing a cavity;

ii) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

iii) a tissue interface layer for contacting a tissue membrane of an animal, said tissue interface layer containing at least one porator, and said tissue interface layer forming the bottom of said poration device;

b) actuating said poration device to form at least one micropore in said tissue membrane;

c) removing said poration device from said tissue membrane; and

d) applying a reservoir drug patch to said microporated area of said tissue membrane after poration.

25. The method according to claim 24 wherein said reservoir drug patch comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing said drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

26. The method according to claim 25 wherein said reservoir drug patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane.

27. The method according to claim 24 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

28. The method according to claim 24 wherein said at least one porator is selected from the group consisting of a probe element, an electromechanical actuator, a microlancet, an array of micro-needles or lancets, a thermal energy ablator, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer.

29. The method according to claim 28 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

30. The method according to claim 24 wherein said tissue interface layer is removably attached to said outer body.

31. The method according to claim 24 further comprising a control button for initiating actuation of said poration device.

32. The drug method according to claim 24 wherein said tissue interface layer further comprises an adhesive layer for attachment of said poration device to said tissue membrane.

33. A method of delivering a drug to a patient in need thereof, comprising the steps of:

a) contacting a poration device to a tissue membrane of said patient, said poration device comprising;

i) an actuator comprising;

A) an outer body defining a top of said actuator, said outer body containing a cavity;

B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

ii) said porator array comprising;

A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

C) a release liner removably attached to said bottom surface; and

b) actuating said poration device to form at least one micropore in said tissue membrane;

c) removing said poration device from said tissue membrane; and

d) applying a reservoir drug patch to said microporated area of said tissue membrane after poration.

34. The method according to claim 33 wherein said reservoir drug patch further comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing a drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

35. The method according to claim 34 wherein said reservoir patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane.

36. The method according to claim 33 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

37. The method according to claim 33 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

38. The method according to claim 33 wherein said porator is removably attached to said actuator.

39. The method according to claim 33 wherein said actuator further comprises a control button for initiating actuation of said poration device.

40. A method of delivering a drug to a patient in need thereof, comprising the steps of:

a) contacting a poration device to a tissue membrane of said patient, said a poration device comprising;

i) an actuator comprising;

A) an outer body defining a top of said actuator, said outer body containing a cavity;

B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

ii) said porator array comprising;

A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

C) an extension tab laterally and removably attached to said bottom surface, said extension tab including an adhesive applied on the bottom thereof, thereby allowing said extension tab to remain on said tissue membrane upon removal of said porator array; and

D) a release liner removably attached to said bottom surface;

b) removing said actuator from said porator array;

c) removing said porator array from said tissue membrane without removing said extension tab; and

d) applying a reservoir drug patch to said microporated area of said tissue membrane, said reservoir drug patch being attached to said extension tab.

41. The method according to claim 40 wherein said reservoir drug patch further comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing said drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

42. The method according to claim 41 wherein said reservoir drug patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane, said method further comprising the step of removing said cover layer prior to applying said drug patch to said microporated tissue membrane.

43. The method according to claim 40 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

44. The method according to claim 40 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

45. The method according to claim 40 wherein said actuator further comprises a control button for initiating actuation of said poration device.

46. A method for enhancing a flux across a biological membrane comprising the steps of:

a) adhering a flux enhancement cell to said biological membrane, said flux enhancement cell comprising a compliant portion which interfaces with said biological membrane, a central portion and a reservoir;

b) applying pressure to said central portion, thereby compressing tissue associated with said biological membrane;

c) pulling said central portion away from said biological membrane while keeping said flux enhancement cell attached to said biological membrane;

d) inducing a permeant composition from said reservoir to flow through a pore in said biological membrane;

e) returning said flux enhancement cell to its original state;

f) removing said flux enhancement cell from said biological membrane.

47. The method according to claim 46 wherein said flux enhancement cell is maintained on said biological membrane during said pulling step by means selected from the group consisting of an adhesive, a pneumatic suction device, a vacuum, or mixtures thereof.

48. The method according to claim 46 wherein said compliant portion is constructed of a material selected from the group consisting of silicone rubber, latex, vinyl, polyurethane, polyethylene.

49. The method according to claim 46 wherein said permeant composition is a drug or other therapeutically effective agent.

50. The method according to claim 46 further comprising controlling said method with a controller containing a microprocessor programmed to perform said method steps.

51. A method for enhancing a flux across a biological membrane comprising the steps of:

a) adhering a flux enhancement cell to said biological membrane, said flux enhancement cell comprising a compliant portion which interfaces with said biological membrane, a central portion and a reservoir;

b) applying pressure to said central portion, thereby compressing tissue associated with said biological membrane;

c) pulling said central portion away from said biological membrane while keeping said flux enhancement cell attached to said biological membrane;

d) reducing pressure in said reservoir, thereby inducing a biological fluid to flow into said reservoir;

e) returning said flux enhancement cell to its original state;

f) removing said flux enhancement cell from said biological membrane.

52. The method according to claim 51 wherein said flux enhancement cell is maintained on said biological membrane during said pulling step by means selected from the group consisting of an adhesive, a pneumatic suction device, a vacuum, or mixtures thereof.

53. The method according to claim 51 wherein said compliant portion is constructed of a material selected from the group consisting of silicone rubber, latex, vinyl, polyurethane, polyethylene.

54. The method according to claim 51 wherein said permeant composition is a drug or other therapeutically effective agent.

55. The method according to claim 51 further comprising controlling said method with a controller containing a microprocessor programmed to perform said method steps.

56. A method of monitoring an analyte extracted from a patient and delivering a permeant composition to said patient, comprising the steps of:

a) contacting a poration device to a tissue membrane of said patient, said poration device comprising;

i) an actuator comprising;

A) an outer body defining a top of said actuator, said outer body containing a cavity;

B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

ii) said porator array comprising;

A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

C) a release liner removably attached to said bottom surface;

b) actuating poration of said tissue membrane using said at least one poration array in said poration device;

c) extracting an analyte from said microporated tissue membrane by way of said at least one micropore array into a first of said reservoirs;

d) analyzing said analyte to determine concentration of same within said tissue membrane; and

e) delivering a permeant composition to said tissue membrane by way of said at least one micropore array for a second of said reservoirs.

57. The method according to claim 56 further comprising a first control button for actuating poration of said membrane.

58. The method according to claim 57 further comprising a second control button for initiating delivery of a permeant composition to said membrane or extraction of an analyte from said membrane.

59. The integrated poration device according to claim 58 wherein two of said additional reservoirs contain different permeant compositions to be applied to said tissue membrane.

60. The method according to claim 56 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

61. A method of delivering two or more biologically active compounds to a patient in need thereof by way of a tissue membrane, said method comprising the steps of:

a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore, said poration device comprising;

i) a actuator comprising;

A) an outer body defining a top of said actuator, said outer body containing a cavity;

B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

ii) said porator array comprising;

A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

C) a release liner removably attached to said bottom surface;

b) applying a first compound contained in a first of said reservoir of said poration device to said tissue membrane by way of said at least one micropore; and

c) applying a second compound contained in a second of said reservoirs of said poration device to said tissue membrane by way of said at least one micropore.

62. The method according to claim 61 wherein said first and second compounds are simultaneously applied to said tissue membrane.

63. The method according to claim 61 wherein said first compound is a first biologically active agent and said second compound is a different biologically active agent.

64. The method according to claim 61 wherein said first compound is a biologically active agent and said second compound is a pharmaceutically acceptable excipient.

65. The method according to claim 61 wherein said first and second compounds are mixed within said poration device prior to being applied to said tissue membrane.

66. A method of facilitating passage of biological compounds across a tissue membrane comprising the steps of:

a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore, said poration device comprising;

i) an actuator comprising;

A) an outer body defining a top of said actuator, said outer body containing a cavity;

B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

ii) said porator array comprising;

A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

C) a release liner removably attached to said bottom surface;

b) applying a first compound contained in a first said reservoirs of said poration device to said tissue membrane by way of said at least one micropore; and

c) extracting a second compound from said tissue membrane and storing said second compound in a second of said reservoirs in said poration device.

67. The method according to claim 66 wherein said steps of applying said first compound to said tissue membrane and extracting said second compound from said tissue membrane are executed simultaneously.

68. The method according to claim 66 wherein said step of extracting said second compound from said tissue membrane is carried out prior to said step of applying said first compound to said tissue membrane.

69. The method according to claim 68 further comprising the step of analyzing said second compound and applying said first compound based on said analysis.

70. A method of manufacturing a drug delivery patch system comprising the steps of:

a) assembling an actuator comprising the steps of;

i) forming an outer body defining a top of said actuator, said outer body containing a cavity;

.

ii) assembling a controller board comprising driving electronics and a battery, and positioning said controller board within said cavity; and

iii) preparing an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;

b) assembling said porator array comprising the steps of;

i) applying a removable adhesive layer to a top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;

ii) forming a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane; and

iii) attaching an extension tab laterally and removably to said bottom surface, and applying an adhesive layer to the bottom of said extension tab, thereby allowing said extension tab to remain on said tissue membrane upon removal of said porator array; and

iv) removably attaching a release liner to said bottom surface; and

c) attaching a reservoir patch to said extension tab, said reservoir patch being applied to said microporated area of said tissue membrane after poration.

71. The method according to claim 70 wherein said reservoir patch further comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing a drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

72. The method according to claim 71 wherein said reservoir patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane.

73. The method according to claim 70 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

74. The method according to claim 70 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

75. The method according to claim 70 wherein said actuator further comprises a control button for initiating poration of said membrane.

76. A method of monitoring an analyte extracted from a patient and delivering a permeant composition to said patient, comprising the steps of:

a) contacting a delivery and extraction patch to a tissue membrane of said patient;

b) actuating poration of said tissue membrane using at least one poration array in said delivery and extraction patch;

c) extracting an analyte from said microporated tissue membrane by way of at least one micropore array;

d) analyzing said analyte to determine concentration of same within said tissue membrane; and

e) delivering a permeant composition to said tissue membrane by way of at least one micropore array.

77. The method according to claim 76 wherein said delivery and extraction patch comprises:

a) a first section comprising a first tissue interface layer and a first reservoir for storing a permeant composition to be applied to a tissue membrane, said first tissue interface membrane further comprising a substrate with a first porator array contained on or within said substrate;

b) a second section comprising a second tissue interface layer and a second reservoir for collecting an analyte from said tissue membrane for analysis, said second tissue interface membrane further comprising a substrate with a second porator array contained on or within said substrate; and

c) an adhesive for adhering said patch to said tissue membrane.

78. The method according to claim 77 wherein said first and second porator arrays are the same porator array.

79. The method according to claim 77 wherein said first and second porator arrays are different porator arrays.

80. The method according to claim 77 wherein said first and second porator arrays are each selected from the group consisting of a probe element, an electro-mechanical actuator, a microlancet, an array of micro-needles or lancets, a thermal energy ablator, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer.

81. The method according to claim 77, wherein said first and second reservoirs each further comprise:

a) a top layer;

b) a middle layer that has at least one cavity for storing a drug or other permeant composition to be applied to said membrane in said first reservoir, and for accepting said analyte in said second reservoir; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane in said first reservoir, and through which said analyte is extracted in said second reservoir.

82. The method according to claim 77 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

83. The method according to claim 77 wherein said first and second porator arrays are each selected from the group consisting of a wire conductor, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a shape memory alloy material and an etched conductive material.

84. A transdermal drug delivery patch system for delivering a drug across a tissue membrane comprising:

a) an actuator;

b) a porator array removably connected to said actuator, said porator array comprising at least one microporator which is actuated by said actuator and forms at least one micropore in said tissue membrane; and

c) a reservoir patch, said reservoir patch separate from said porator array and applied to said tissue membrane following formation of said at least one micropore.

85. The transdermal drug delivery patch system according to claim 84 wherein said actuator further comprises:

a) an outer body defining a top of said actuator, said outer body containing a cavity;

b) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity; and

c) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode.

86. The transdermal drug delivery patch system according to claim 84 wherein said reservoir patch further comprises:

a) a top layer;

b) a middle layer that has at least one cavity for containing a drug or other permeant composition to be applied to said membrane; and

c) a bottom layer, said bottom layer containing pores through which said drug is applied to said tissue membrane, and said bottom layer containing an adhesive for attachment of said reservoir patch to said microporated area of said tissue membrane.

87. The transdermal drug delivery patch system according to claim 86 wherein said reservoir patch further comprises a cover layer attached to said bottom layer to retain said drug in said middle layer until said patch is applied to said tissue membrane.

88. The transdermal drug delivery patch system according to claim 84 wherein said tissue interface layer comprises a material selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

89. The transdermal drug delivery patch system according to claim 84 wherein said at least one porator is a probe element, said probe element being a heated resistive element.

90. The transdermal drug delivery patch system according to claim 84 wherein said actuator further comprises a control button for initiating poration of said membrane.