WO1991011216A1

WO1991011216A1 - Iontophoretic transfer electrode and method

Info

Publication number: WO1991011216A1
Application number: PCT/US1991/000279
Authority: WO
Inventors: Robert Steven Hillman; John Michael Pawelchak
Original assignee: Gensia Pharmaceuticals, Inc.
Priority date: 1990-01-26
Filing date: 1991-01-14
Publication date: 1991-08-08
Also published as: IE910234A1; AU7242091A

Abstract

An electrode and method for iontophoretic transdermal drug delivery includes an electrode having disposed therein a gel reservoir and a silver/silver chloride conductive element in laterally coextensive adjacent engagement. An adhesive circumferential frame houses the reservoir and conductive element and a connector is attached to the conductive element at a location laterally adjacent the reservoir, for connecting the electrode to an outside power source.

Description

DESCRIPTION

lontophoretic Transfer Electrode and Method

Field of the Invention

The present invention relates to transdermal iontophoretic drug delivery, and more particularly, to iontophoresis electrodes and methods for their use. Iontophoresis is the transport of ionized or charged species by application of an electrical current. Transdermal iontophoresis is the transport of an ionic drug into a patient's skin by application of a current through a drug containing electrode placed against the skin. A second electrode, termed the return or indiffe¬ rent electrode, is also placed against the skin, normally several inches from the first. The current is evoked by applying a potential between the electrodes in either a constant or pulsed DC or AG mode. It carries the ionized drug "through" the stratum corneum into the dermis where the drug diffuses into the capillaries situated near the dermal-epidermal junction, to the systemic circulation.

Flux refers to the amount of drug transported across the skin into the circulation per area per unit time. Flux is proportional to the applied electrical potential, the drug concentration and the electrode area. To achieve clinically effective transdermal iontophoretic delivery, the drug must be transported in sufficient quantity under the application of DC currents that do not damage the skin. Generally, the upper limit of current density is taken to be 0.5 mA/cm2. Other limits on available flux include drug solubility, the partition coefficient of drug in the stratum corneum and. the drug's iontophoretic mobility. Various electrodes and iontophoresis devices have been proposed. See, e.g.. U.S. Patent Nos. 3,977,392; 4,557,723; 4,640,689; 4,383,529; 4,474,570; and 4,722,726 and European Patent Nos. 182,520 and 252,732. The present invention provides an electrode for iontophoretic delivery which is capable of delivering pharmacologically effective quantities of drugs within the limits of acceptable current densities and which should be well tolerated by the patient on whom the electrode is used.

Summary of the Invention

The present invention is directed to a novel transdermal iontophoresis electrode having optimal flux capability. To that end, a drug reservoir is provided in combination with a conductive member of unique design in a compact adhesive electrode. Means are provided for ensuring uniform current distribution and for minimizing undesirable ions.

Brief Description of the Drawings

Figure 1 is a top view of an electrode constructed in accordance with the present invention.

Figure 2 is a bottom view of the electrode shown in

Figure 1. Figure 3 is a cross-sectional view taken along line

3-3 in Figure 1 of the electrode shown in Figures 1 and 2.

Figure 4 is a cross-sectional view taken along line

4-4 in Figure 1 of the electrode shown in Figures 1 and 2.

Figure 5 is a perspective view of the electrode shown in Figures 1 to 4.

Detailed Description of the Preferred Embodiment

Referring to the Figures, a drug-containing electrode is shown as being generally ovular, although many other shapes could be advantageously employed, provided the electrode is conformable to the area of the body where it is to be applied. The electrode includes interiorly disposed drug delivery components and an exterior support framework. The drug delivery coirφonents include a gel reservoir or pad sandwiched between a conductive strip and an exterior mesh element. The gel reservoir, conductive strip and mesh elements are laterally coextensive to provide uniform current distribution. The surface area of the reservoir may be up to about 10 cm2, but preferably is only as large as required to keep current density below 0.5 amp/cm2, since increased pad area reduces current density, which may be a major factor in pH change, damage to the patient's skin and build up of a drug depot. The preferred reservoir contains about 1 ml volume and has an area of 1.8 cm2. The depth is in a range of 3-10 mm and is preferably about 5 mm.

The conductive strip is formed from a silver strip chlorided by an electrode discharge process impregnated mylar. As thus formed, the electrode undergoes an oxidation reduction reaction during iontophoretic delivery whereby silver chloride is produced. This provides a highly uniform silver-silver chloride contact boundary that enhances flux and minimizes skin irritation by counteracting the formation of highly mobile ions such as H+, which not only compete with the ionized drug for available current, but also decrease pH.

The mesh element, which may be nylon, polyester, cellulose, rayon or other suitable material, helps retain the drug in the gel reservoir during electrode application while allowing substantially unrestricted flow when the electrode is attached to the patient and the mesh element is compressed between the skin and the reservoir. The drug delivery components are encased in a circumferentially arranged support frame comprising a continuous adhesive foam member. The support frame is shown to be generally rectangular in cross-section although other shapes could be employed. Preferably, the support frame is slightly thinner than the drug delivery components so that when the conductive strip is flush with one side of the frame, the nylon mesh element extends slightly beyond the other side of the frame to ensure contact of the mesh with the patient's skin. Moreover, it is preferred that the drug delivery elements be slightly larger than the interior of the support frame so as to be retained therein by compressive engagement.

As shown in the Figures, an insulative vinyl backing member may be secured to the top of the support frame. Mounted to and extending through the backing member is a conductive snap connector. The snap is electrically attached to a tongue extending from the conductive strip and is adapted for connection to an external power and control source (not shown) .

Current from the power and control source enters the electrode through the snap, at a location laterally disposed from the drug reservoir. The current flows uniformly through the reservoir by means of the conductive strip, which is coextensive therewith, and thereafter through the patient to a second, indifferent electrode (not shown) . The indifferent electrode is constructed in accordance with the drug delivery electrode herein described. For ease of identification, the drug and indifferent electrodes may be color coded.

For storage purposes, a release liner may be removably attached to the bottom of the support frame to help retain the gel during storage and shipping.

Accordingly, a transdermal iontophoresis delivery electrode and method has been disclosed. While what has been hereinbefore described represents a embodiment of the invention, it will be recognized that other variations are possible, and the invention is not to be limited except as set forth in the claims appended hereto.

Claims

1. An electrode for iontophoretic delivery comprising a gel reservoir containing a substance to be iontophoretically delivered, a conductive element having a central portion disposed in adjacent engagement with said reservoir and being laterally coextensive therewith, said conductive element having a tongue portion extending laterally from said central conductor portion, and a connector electrically attached to said conductor tongue portion at a location laterally disposed from said reservoir.

2. The electrode set forth in claim 1 wherein said electrode is made from silver and has a silver chloride surface coating.

3. The electrode set forth in claim 1 further including an adhesive frame circumferentially disposed around said reservoir and said central portion of said conductive element.

4. The electrode set forth in claim 1 further, including a mesh element disposed in adjacent engagement with a portion of said reservoir which is not in engagement with said conductive element, said reservoir being sandwiched between said mesh element and said conductive element.

5. An electrode for iontophoretic delivery comprising a generally planar gel reservoir for containing a substance to be iontophoretically delivered and a generally planar silver/silver chloride conductive element in laterally coextensive adjacent engagement, said conduc- tive element having a tongue portion extending laterally therefrom, and a connector electrically attached to said tongue, whereby electrical current may be uniformly distributed through said reservoir.

6. The electrode set forth in claim 5 further including an adhesive frame disposed circumferentially about said reservoir and said conductive element, and an insulative backing extending across one side of said frame, through which said connector extends.

7. The electrode set forth in claim 6 further including a mesh element in laterally coextensive adjacent engagement with said reservoir, said reservoir being sandwiched between said mesh element and said conductive element.

8. The electrode set forth in claim 7 further including a release liner extending across the side of said frame not covered by said insulative backing.

9. An electrode for iontophoretic delivery comprising a generally toroidal adhesive support frame having disposed by compressive support in the open interior thereof a multilayer iontophoretic delivery system comprising a generally planar silver/silver chloride conductive element, a gel reservoir element for containing a substance to be iontophoretically delivered and a mesh element, said conductive element, reservoir and mesh elements being laterally coextensive and being arranged in a sandwich with said reservoir being disposed between said conductive and mesh elements, said conductive element further including a tongue extending laterally therefrom through a recess in said frame, said frame further including a generally planar backing insulator attached to one side of said frame and a connector electrically attached to said tongue and extending through and mounted to said backing insulator, said connector being adapted for connection to an external power source, said electrode further including a release liner disposed on side of said frame opposite said backing insulator. said reservoir having a surface area of not less than substantially 0.64 cm .

10. A method for iontophoretic delivery comprising securing to a patient's skin a first electrode comprising a gel reservoir containing a substance to be iontophoreti¬ cally delivered and a conductor having a central portion disposed in adjacent engagement with said reservoir and being laterally coextensive therewith, and a conductor having a tongue portion extending laterally from said central conductor portion, said conductor being silver and having a silver chloride coating thereon, said electrode further comprising a connector electrically attached to said conductor at a location laterally disposed from said reservoir, said method further comprising securing a second electrode to the patient a short distance from said first electrode, and applying an electrical potential across said electrodes.