Iontophoretic drug delivery

• US 5,135,477 A
• Filed: 02/10/1988
• Issued: 08/04/1992
• Est. Priority Date: 10/29/1984
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Phipps, Joseph B., Lattin, Gary A., Untereker, Darrel F.
• Primary Examiner(s): Morgan, Kriellion S.
• Application Number:
  US07/154,566
• Time in Patent Office: 1,637 Days
• Field of Search: 604/20, 128/172.1, 128/798
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

Improved methods of ionophoretic drug delivery are described. By the intentional selection of drug(s) with specific characteristics, of ionotophoresis device, components or both permits the efficiency of drug delivery is increased.

Claims

1. A method of increasing the efficiency of an iontophoretic electrode for delivery of an ionic drug having a positive charge by minimizing delivery of mobile cations other than said ionic drug, hereafter referred to as competing cations, comprising the following steps:

forming a reservoir containing said ionic drug with a negatively charged counter-ion, said reservoir being substantially free of cations which can compete with the drug ions for carrying charge from the reservoir to a body surface, the reservoir also being permeable to said ionic drug;

applying to said reservoir an electrically conductive member comprising a sacrificial material readily oxidizable when said conductive member is in contact with said reservoir and a positive voltage is applied to said conductive member, said material when oxidized readily combining with said counter-ion to form a compound which is substantially immobile within said reservoir during the application of said positive voltage;

placing said reservoir containing said ionic drug in drug transmitting relation to the body surface of a patient; and

while said reservoir is in drug transmitting relation to the body surface of said patient and said conductive member is applied to said reservoir, applying a positive voltage to said conductive member to oxidize said material and to drive said ionic drug through the body surface of said patient, whereby said ionic drug is driven through said body surface substantially without cationic competition.

2. A method according to claim 1 wherein said material is silver and wherein said counter-ion is chloride.

3. A method according to claim 1 wherein said material is silver and wherein said counter-ion is ferrocyanide.

4. A method according to claim 1 wherein said material is copper and said counter-ion is ferrocyanide.

5. A method according to claim 1 or claim 2 wherein said ionic drug comprises ionic lithium.

6. A method according to claim 1 or claim 2 wherein said ionic drug comprises ionic potassium.

7. A method according to claim 1 or claim 2 wherein said step of incorporating said ionic drug comprises incorporating propranalol with said negatively charged counter-ion.

8. A method according to claim 7 wherein said propranalol is provided in the form of propranalol hydrochloride.

10. A method according to claim 1 wherein said material is tin and said counterion is phosphate.

11. A method according to claim 1 wherein said material is zinc and said counterion is phosphate.

12. A method according to claim 1 wherein said material is zinc and said counterion is oxalate.

13. A method according to claim 1 wherein said material is copper and said counterion is citrate.

20. The method of claim 1, 9, 14 or 15 wherein the body surface is selected from the group consisting of skin and mucosal membrane.

9. A method of increasing efficiency of delivery in an iontophoretic electrode for delivery of an ionic drug having a positive charge by minimizing delivery of competing cations, comprising the steps of:

applying an electrically conductive member to a reservoir containing said ionic drug compounded with a negatively charged counter-ion, said reservoir being substantially free of cations which can compete with the drug ions for carrying charge from the reservoir to a body surface, the reservoir also being permeable to said ionic drug, said electrically conductive member comprising a sacrificial material readily oxidizable when said conductive member is in contact with said reservoir and a positive voltage is applied to said conductive member, said material when oxidized readily combining with said counter-ion and which when so combined forms a compound which is substantially immobile within said reservoir during the application of said positive voltage;

placing said reservoir in drug transmitting relation to the body surface of the patient; and

while said reservoir is in drug transmitting relation to the body surface of said patient and said conductive member is applied to said reservoir, applying a voltage to said conductive member to oxidize said material and to drive said ionic drug through the body surface of said patient substantially free of cationic competition.

14. A method of increasing the efficiency of delivery of an ionic drug having a negative charge from an iontophoretic electrode by minimizing the delivery of mobile anions other than said ionic drug, comprising the follow steps:

forming a reservoir containing the drug with a positively charged counter-ion, said reservoir being substantially free of anions which can compete with the drug ions for carrying charge from the reservoir to a body surface, the reservoir also being permeable to said ionic drug;

applying to said reservoir an electrically conductive member comprising a sacrificial material which is readily reducible when said conductive member is in contact with said reservoir and a negative voltage is applied to said conductive member, said material when reduced forming an anion which is readily combined with said counter-ion to form a compound which is immobile within said reservoir during the application of said negative voltage;

placing said reservoir in drug transmitting relation to the body surface of a patient; and

while said reservoir is in drug transmitting relation to the body surface of said patient and said conductive member is applied to said reservoir, applying a negative voltage to said conductive member to reduce said material and to drive said ionic drug through the body surface of said patient, whereby said ionic drug is driven through said body surface substantially without anionic competition.

16. The method of claim 14 or 15, wherein the sacrificial material comprises chloridized silver and the anion which is formed when the material is reduced comprises chloride anion.

17. The method of claim 14 or 15, wherein the counter-ion of the drug comprises a reducible metal.

18. The method of claim 17, wherein the reducible metal is selected from the group consisting of silver and copper.

19. The method of claim 14 or 15, wherein the ionic drug comprises salicylate.

15. A method of increasing efficiency of delivery of an ionic drug having a negative charge from an iontophoretic electrode by minimizing delivery of competing anions, comprising the steps of:

applying an electrically conductive member to a reservoir containing said ionic drug compounded with a positively charged counter-ion, said reservoir being substantially free of anions which can compete with the drug ions for carrying charge from the reservoir to a body surface, said reservoir also being permeable to said ionic drug, said electrically conductive member comprising a sacrificial material which is readily reducible when said conductive member is in contact with said reservoir and a negative voltage is applied to said conductive member, said material when reduced forming an anion which is readily combined with said counter-ion and which when so combined forms a compound which is substantially immobile within said reservoir during the application of said negative voltage;

placing said reservoir in drug transmitting relation to the body surface of the patient; and

while said reservoir is in drug transmitting relation to the body surface of said patient and said conductive member is applied to said reservoir, applying a voltage to said conductive member to reduce said material and to drive said ionic drug through the body surface of said patient substantially free of anionic competition.