Device and method of iontophoretic drug delivery

• US 5,993,435 A
• Filed: 08/24/1998
• Issued: 11/30/1999
• Est. Priority Date: 04/30/1990
• 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:
  US09/139,036
• Time in Patent Office: 463 Days
• Field of Search: 604/20, 604/501, 607/149, 607/152-153
• US Class Current: 604/501
• 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. A method of delivering an agent through a patient body surface from 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 including an agent reservoir containing the agent and adapted to be placed in agent transmitting relation with the body surface and a donor electrode adapted to be electrically connected to the source of electrical power, comprising:

a) placing a non-hydrated selectively permeable membrane intermediate the agent reservoir and the donor electrode, (i) the membrane, in a non-hydrated condition, being substantially impermeable to ionic species, (ii) the membrane, once hydrated, being permeable to species of less than a predetermined molecular weight and substantially less permeable to species of greater than the predetermined molecular weight;

b) selecting an agent for delivery from the agent reservoir, the agent being capable of dissociating into agent ions and counter ions of opposite charge, the agent ions having less than the predetermined molecular weight, the counter ions having greater than the predetermined molecular weight;

c) hydrating the membrane at about the time the device is placed on the body surface; and

d) delivering the agent ions through the body surface.

2. The method of claim 1, further comprising placing a donor electrolyte reservoir intermediate the donor electrode and the membrane, and selecting an electrolyte for the electrolyte reservoir, the electrolyte being capable of dissociating into positively charged and negatively charged electrolyte ions, the electrolyte ions of similar charge to the agent ions having less than the predetermined molecular weight, the electrolyte ions of similar charge to the counter ions having greater than the predetermined molecular weight.

3. The method of claim 1, wherein the selectively permeable membrane has 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.

4. The method of claim 3, wherein R_mass is less than about 0.1.

5. The method of claim 1, wherein the hydrated selectively permeable membrane exhibits an area resistance of less than about 50 kohm.cm².

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

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

8. The method of claim 1, wherein the body surface is selected from intact skin and mucosal membranes.

9. The method of claim 1, wherein the agent comprises a drug capable of dissociating into drug ions having a molecular weight of less than about 100 daltons and counter ions having a molecular weight of greater than about 300 daltons.