Device and method of iontophoretic drug delivery

• US 5,857,992 A
• Filed: 02/27/1996
• Issued: 01/12/1999
• Est. Priority Date: 10/27/1992
• 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:
  US08/607,534
• Time in Patent Office: 1,050 Days
• Field of Search: 604/20, 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 and counter electrode assemblies, the donor electrode assembly comprising:

an agent reservoir containing an agent and adapted to be placed in agent transmitting relation with a body surface;

a donor electrode adapted to be electrically connected to the source of electrical power;

a non-hydrated, selectively-permeable membrane between the donor electrode and the agent reservoir and upon hydration being permeable to molecules less than a predetermined molecular weight and substantially less permeable to molecules greater than the predetermined molecular weight; and

,

an electrolyte reservoir containing an electrolyte intermediate the donor electrode and the non-hydrated, selectively permeable membrane,

wherein the agent dissociates into agent ions having a molecular weight less than the predetermined molecular weight and counter ions having a molecular weight greater than the predetermined molecular weight,

wherein the electrolyte dissociates into (i) electrolyte ions having a similar sign charge as the agent ions, and (ii) electrolyte ions having a similar sign charge as the agent counter ions, the electrolyte ions having the same charge as the agent ions having a molecular weight less than the predetermined molecular weight, and the electrolyte ions having the same charge as the counter ions having a molecular weight greater than the predetermined molecular weight; and

wherein the membrane is capable of being hydrated upon operation of the device.

2. The device of claim 1, wherein the hydrated selectively-permeable membrane has a mass ratio, R_mass of less than about 0.3, the mass ratio being defined as:

##EQU2## where;

M_perm is the mass of agent ions that permeate 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 hydrated, selectively-permeable membrane exhibits an area resistance of less than about 50 kohm.cm².

5. The device of claim 1, wherein the hydrated, selectively-permeable membrane exhibits an area resistance of less than about 5 kohm.cm².

6. The device of claim 1, wherein the hydrated, selectively-permeable membrane exhibits an area resistance of less than about 1 kohm.cm².

7. The device of claim 1, wherein the agent counter ions are ions selected from the group consisting of tetraalkylammonium, cholestyramine, gluconate, hyaluronate, alginate, dextran carbonate, aminated styrene, polyvinylimine, polyethyleneimine, poly(vinly-4alkylpyridinium), (poly(methylene-N,N-dimethylpiperidinium), poly(vinylbenzyltrimethylammonium), polyacrylate, polymethacrylate, polystyrene sulfonate, lauryl sulfate, tartrate, tetradecly sulfate and dextran sulfate ions.

8. The device of claim 1, wherein the body surface is intact skin or mucosal membranes.

9. The device of claim 1, wherein the agent ions have a molecular weight less than about 100 daltons and counter ions having a molecular weight greater than about 300 daltons.

10. The device of claim 1, wherein the predetermined molecular weight is from about 100 to about 10,000 daltons.

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

12. 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 a second electrolyte reservoir containing a second electrolyte adapted to be placed in electrolyte transmitting relation with a body surface.

13. The device of claim 12, wherein the second electrolyte comprises a pharmacologically suitable salt.

14. The device of claim 12, wherein the donor electrode assembly and the counter electrode assembly are separated by an electrical insulator.

15. The device of claim 1, wherein the electrolyte ions having a similar sign charge as the agent counter ions are selected from the group consisting of tetraalkylammonium, cholestyramine, gluconate, hyaluronate, alginate, dextran carbonate, aminated styrene, polyvinylimine, polyethyleneimine, poly(vinyl-4-alkylpyridinium),poly(methylene-N,N-dimethylpiperidinium), poly(vinylbenzyl trimethylammonium), polyacrylate, polymethacrylate, polystyrene sulfonate, lauryl sulfate, tartrate, tetradecyl sulfate and dextran sulfate ions.

16. The device of claim 1, wherein the electrolyte ions having a similar sign charge as the agent ions are selected from the group consisting of alkali metal, alkaline earth metal, halogen, ammonium, phosphate, sulfate, perchlorate, carbonate, citrate, acetate, benzoate, oxylate and borate ions.

17. The device of claim 1, wherein the electrolyte ions having a similar sign charge as the agent ions are selected from the group consisting of sodium, potassium and chloride ions.