Device and method of iontophoretic drug delivery

• US 5,647,844 A
• Filed: 02/27/1996
• Issued: 07/15/1997
• Est. Priority Date: 10/03/1988
• Status: Expired due to Fees

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Gyory, J. Richard, Theeuwes, Felix, Haak, Ronald P.
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/607,533
• Time in Patent Office: 504 Days
• Field of Search: 604/201, 604/289, 604/890.1, 607/115, 210/502.1, 210/638, 424/449
• 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

A selectively permeable membrane (14) is positioned between the agent reservoir (15) and the electrode (11) of a donor electrode assembly (8) in an iontophoretic delivery device (10). Optionally, an electrolyte reservoir (13) is positioned intermediate the electrode (11) and the agent reservoir (15). In certain embodiments, the membrane (14) is permeable to species of less than a predetermined molecular weight and substantially less permeable to species of greater than the predetermined molecular weight. The agent is capable of dissociating into agent ions and counter ions. The size selectivity of the membrane (14), the molecular weight of the agent ions, the molecular weight of the counter ions, and optionally the molecular weight of the electrolyte ions are selected to (A) inhibit agent ions from interacting with the electrode (11), and from permeating into the electrolyte reservoir (13), where they might otherwise be degraded and (B) inhibit electrolyte ions, having a charge similar to that of the agent ions, from permeating into the agent reservoir (15) and competing with the agent ions for iontophoretic delivery into the patient.

Claims

1. An electrically powered iontophoretic agent delivery device including a donor electrode assembly, a counter electrode assembly and a source of electrical power adapted to be electrically connected to the donor electrode assembly and the counter electrode assembly, the donor electrode assembly comprising:

an agent reservoir containing an agent and adapted to be placed in agent transmitting relation with a body surface, the agent being at least partially dissociated into agent ions and counter ions of opposite charge during use of the device;

a selectively permeable membrane containing a chelating agent, the selectively permeable membrane being positioned within the donor electrode assembly intermediate the donor electrode and the agent reservoir, the chelating agent being one which traps ions having a charge similar to the charge of the agent ions, the membrane being permeable to species having a charge similar to the charge of the counter ions and substantially less permeable to species having a charge similar to the charge of the agent ions.

2. The device of claim 1, wherein the selectively permeable membrane exhibits, during use of the device for iontophoretic delivery of the ionized agent, a mass ratio, R_mass for the agent ions through the membrane, of less than about 0.3, the mass ratio being defined as:

##EQU2## where;

M_perm is the mass of agent ions which permeates through the membrane during the operational life of the device; and

M_res is the total mass of agent ions initially contained in the agent reservoir.

3. The device of claim 2, wherein R_mass is less than about 0.1.

4. The device of claim 1, wherein the donor electrode is comprised of an oxidizable metal, and the chelating agent traps metal ions produced during oxidation of the metal electrode.

5. The device of claim 1, wherein the membrane comprises cross-linked hydrogel.

6. The device of claim 5, wherein the hydrogel is selected from the group consisting of polyvinylalcohol, polyacrylamide, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, polyacrylic acid, polyvinyl pyrrolidone, hydroxyethylmethacrylate, albumin, gelatin and cellulosic polymers.

7. The device of claim 1, wherein the chelating agent comprises EDTA.

8. The device of claim 1, wherein the selectively permeable membrane exhibits, during use of the device for iontophoretic delivery of said agent, an area resistance of less than about 50 kohm.cm².

9. The device of claim 1, wherein the selectively permeable membrane exhibits, during use of the device for iontophoretic delivery of said agent, an area resistance of less than about 5 kohm.cm².

10. The device of claim 1, wherein the selectively permeable membrane exhibits, during use of the device for iontophoretic delivery of said agent, an area resistance of less than about 1 kohm.cm².

11. The device of claim 1, wherein the counter ions are selected from the group consisting of sodium, potassium, and chloride ions.

12. The device of claim 1, wherein the device is adapted to be placed on a body surface selected from intact skin and mucosal membranes.

13. The device of claim 1, wherein the agent is a drug.

14. The device of claim 1, wherein the agent is selected from the group consisting of peptides, polypeptides, proteins and other macromolecules.

15. The device of claim 1, wherein the source of electrical power comprises a battery.

16. The device of claim 1, wherein the counter electrode assembly comprises a counter electrode adapted to be electrically connected to the source of electrical power and an electrolyte reservoir adapted to be placed in electrolyte transmitting relation with a body surface.

17. The device of claim 16, wherein the electrolyte in the counter electrode assembly comprises a pharmacologically acceptable salt.

18. The device of claim 17, wherein the donor electrode assembly and the counter electrode assembly are separated by an electrical insulator.

19. The device of claim 1, including a donor electrolyte reservoir intermediate the donor electrode and the membrane, the electrolyte in the donor electrolyte reservoir being capable of dissociating into positively charged and negatively charged electrolyte ions.