Method and apparatus for iontophoretic drug delivery

• US 4,722,726 A
• Filed: 02/12/1986
• Issued: 02/02/1988
• Est. Priority Date: 02/12/1986
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: Key Pharmaceuticals, Inc. (Merck & Co., Inc.)
• Inventors: Deriel, Stanton R., Sanderson, John E.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Costantino, Mario
• Application Number:
  US06/828,794
• Time in Patent Office: 720 Days
• Field of Search: 604/20, 604/891, 604/892, 604/896, 604/897, 128/783, 128/798, 128/803, 128/799
• US Class Current: 604/20
• 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: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir

Abstract

A device for iontophoretic delivery of active ingredient to a patient, that includes an electrode, a first cavity for holding a solution of at least partially active ingredient in ionizing form to be delivered to a patient, a member for maintaining a solution in the first cavity while allowing passage of active ingredient from the first cavity, and an ion exchange member separating the electrode and the first cavity for inhibiting the flow of ions having a charge similar to the charge of the ionized form of the active ingredient from the electrode means to the first cavity is disclosed. A method for iontophoretic delivery of active ingredients to a patient is also disclosed.

Claims

1. An electrode device for iontophoretic delivery of an at least partially ionized active ingredient through the skin of a patient, comprising:

(a) a first containment means defining a first chamber for containing an electrolyte;

(b) an electrical connection in electrical contact with said first chamber defined by said first containment means, for electrically contacting an electrolyte within said first chamber;

(c) a second containment means defining a second chamber for containing an active ingredient in at least partially ionized form and for iontophoretically delivering said at least partially ionized ingredient into the skin of a patient, said second containment means being separated from said first containment means;

(d) an ion mobility inhibiting means separating said first and second containment means, capable of passing current from the first containment means to said second containment means while inhibiting the flow of electrolytic ions having a charge like that of the at least partially ionized active ingredient from said first containment means into said second containment means and allowing the flow from the second containment means to the first containment means of ions having a charge which is different from the charge of the at least partially ionized active ingredient, said ion mobility inhibiting means being spacially separated from said electrical contact, and

(e) maintaining means for maintaining the unionized active ingredient within the second cavity, while allowing electrical current and said at least partially ionized active ingredient to pass from said second containment means into the skin of a patient during iontophoretic treatment.

2. The device of claim 1, wherein the ion mobility inhibiting means comprises an ion exchange membrane.

3. The device of claim 1 further comprising electrolyte in said first containment means, said electrolyte further comprising buffering means for neutralizing ions produced at said electrode.

4. The device of claim 1, wherein the electrode is an anode.

5. The device of claim 1, wherein the electrode is a cathode.

6. The device of claim 1, further comprising active ingredient in a solution in said second containment means, said solution further comprising buffering means for the solution, wherein the ions of the buffering means of like charge to the active ingredient have a limited ionic mobility of less than 1×

10^-4 cm² /volt-sec.

7. The device of claim 3, wherein the electrolyte means is in the form of a gel.

8. The device of claim 1, further comprising a filling means in communication with said second containment means.

9. A method for iontophoretic delivery of active ingredient to a patient, comprising the steps of:

(a) applying to the skin surface of the patient a first electrode device as described in claim 1, said device further comprising electrolyte in said first containment means and active ingredient in said second containment means;

(b) applying to the skin surface of the patient a second electrode device spaced from said first device; and

(c) supplying current to the electrodes of said first electrode device and said second electrode device to cause migration of an effective amount of the active ingredient into the patient from said first electrode device.

10. The method of claim 9, wherein said first and second electrode devices are housed in a unitary body.

11. The method of claim 9, wherein the skin surface below said first electrode device is pretreated iontophoretically with a solution of a surface active agent, said surface active agent having a charge opposite that of the active ingredient ions.

12. The method of claim 9, wherein the active ingredient is contained in a solution and which further comprises incorporating buffering means into this solution, wherein the ions of the buffering means of like charge to the charge of the active ingredient have a limiting ionic mobility of less than 1×

10^-4 cm² /volt-sec.

13. The method of claim 9, wherein the active ingredient is in basic form and is associated with a pharmaceutically acceptable weak acid.

14. The method of claim 13, wherein the pharmaceutically acceptable weak acid is selected from the group consisting of acetic acid, maleic acid, and succinic acid.

15. The method of claim 9, wherein the active ingredient is in acidic form and is associated with a pharmaceutically acceptable weak base.

16. The method of claim 15, wherein the pharmaceutically acceptable weak base is ammonia.

23. A method for iontophoretic delivery of an at least partially ionized active ingredient to the skin of a patient, comprising the steps of:

(a) applying to the skin surface of said patient a first device of claim 1;

(b) applying to said skin surface a second electrode spaced from said first device; and

(c) supplying current to said first device and second electrode sufficient to cause migration of an effective amount of the at least partially ionized active ingredient into the skin of said patient from said first electrode device.

24. The method of claim 23 further comprising pretreating the skin below said first electrode device with a surface active agent having a charge opposite to that of the at least partially ionized active ingredient and iontophoretically delivering said surface active agent into the skin of said patient.

25. A method for iontophoretic delivery of an active ingredient which is in either anionic or cationic form to the skin of a patient, comprising:

(a) pretreating the skin with a cationic or anionic surfactant, respectively;

(b) iontophoretically delivering said surfactant into the skin of a patient;

(c) applying to the skin surface a first electrode device of claim 1;

(d) applying to the skin surface a second electrode spaced from said first electrode device; and

(e) supplying current to said first electrode device and second electrode to cause migration of an effective amount of the at least partially ionized active ingredient into the skin of said patient.

17. A method for iontophoretic delivery of active ingredient which is in either anionic or cationic form to a patient, comprising pretreating the skin with a cationic or anionic surfactant, respectively;

iontophoretically delivering said surfactant into the skin of a patient;

applying to the skin surface of the patient a first electrode device that includes an electrode and an associated ionized active ingredient, applying to the skin surface of the patient a second electrode device spaced from said first electrode device, and supplying current to the electrode devices to cause migration of an effective amount of the active ingredient into the patient.

18. A method for iontophoretic delivery of active ingredient to a patient, comprising applying to the skin surface of the patient a first electrode device that includes an electrode and an associated ionized active ingredient, applying to the skin surface of the patient a second electrode device spaced from said first electrode device, and supplying current to the electrode devices to cause migration of an effective amount of the active ingredient into the patient, said active ingredient being in basic form and being associated with a pharmaceutically acceptable weak acid.

19. The method of claim 18, wherein the weak acid is selected from the group consisting of maleic acid, acetic acid and succinic acid.

20. A method for iontophoretic delivery of active ingredient to a patient, comprising applying to the skin surface of the patient a first electrode device that includes an electrode and an associated ionized active ingredient, applying to the skin surface of the patient a second electrode device spaced from said first electrode devices, and supplying current to the electrode devices to cause migration of an effective amount of the active ingredient into the patient, said active ingredient being in acidic form and being associated with a pharmaceutically acceptable weak base.

21. The method of claim 20, wherein the weak base is ammonia.

22. A method for iontophoretic delivery of active ingredient to a patient, comprising applying to the skin surface of the patient a first electrode device that includes an electrode and an associated at least partially ionized active ingredient, applying to the skin surface of the patient a second electrode device spaced from said first electrode device, supplying current to the electrode devices to cause migration of a therapeutically effective amount of the active ingredient into the patient, and associating said active ingredient with buffering means, wherein the ions of said buffering means of like charge to the active ingredient have a limiting ionic mobility of less than 1×

10^-4 cm² /volt-sec.