Transdermal systems for the delivery of therapeutic agents including granisetron using iontophoresis

• US 8,463,373 B2
• Filed: 11/29/2010
• Issued: 06/11/2013
• Est. Priority Date: 04/22/2005
• Status: Active Grant

• Current Assignee: Teva Pharmaceuticals International GmbH (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teikoku Pharma USA Incorporated (Teikoku Seiyaku)
• Inventors: Anderson, Carter R., Sembrowich, Walter L., Morris, Russell L., Cohen, Robert
• Primary Examiner(s): Mendez, Manuel
• Assistant Examiner(s): HOLLOWAY, IAN KNOBEL
• Application Number:
  US12/955,043
• Publication Number:
  US 20110087154A1
• Time in Patent Office: 925 Days
• Field of Search: 604/20, 604/501, 604/67, 600/573
• 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 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/044 Shape of the electrode
• 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

A disposable skin-worn device for the transdermal delivery at least one dose of charged therapeutic substances, including granisetron, by iontophoresis, the device comprising a donor reservoir containing an amount of a therapeutic substance to be delivered transdermally by iontophoresis, a counter reservoir, a source of electric power connected in a circuit between the donor reservoir and the counter reservoir and a control system for controlling current flow in the circuit to enable at least one dose of the therapeutic substance to be delivered transdermally by iontophoresis and wherein the control system includes a control element selected from the group consisting of a sensor activated by an external signal and a switch.

Claims

1. A method of providing transdermal delivery of a plurality of doses of a charged therapeutic substance comprising:

(a) providing a skin-worn device comprising;

(1) a donor reservoir containing an amount of a therapeutic substance to be delivered transdermally by iontophoresis, said donor reservoir further including circuit elements configured to deliver a plurality of successive doses of a therapeutic substance by sequentially selectively connecting a plurality of separate sources of reactive material in said circuit in a manner such that each dose is delivered by a different source of reactive material;

(2) a counter reservoir;

(3) a source of electric power connected in a circuit between said donor reservoir and said counter reservoir; and

(4) a control system for controlling current flow in said circuit and configured to enable the plurality of successive doses of said therapeutic substance to be administered from said donor reservoir;

(b) applying said skin-worn device to the skin of a patient; and

(c) using said control system to control current flow in said circuit to provide a plurality of doses of said therapeutic substance.

2. A method as in claim 1 wherein said separate sources of reactive material are donor electrodes and said control system further comprises a switch operable for selectively connecting said donor electrodes into said circuit.

3. A method as in claim 1 wherein a circuit is completed and a first dose of said therapeutic substance is provided automatically upon application of said device to a patient'"'"'s skin.

4. A method as in claim 2 wherein said switch is a two-position switch used by said patient to administer a second dosage when desired.

5. A method as in claim 1 wherein said therapeutic substance includes an anti-emesis agent.

6. A method as in claim 4 wherein said therapeutic substance includes an anti-emesis agent.

7. A method as in claim 5 wherein said anti-emesis agent comprises granisetron.

8. A method as in claim 6 wherein said anti-emesis agent comprises granisetron.

9. A method as in claim 7 wherein each said dose is between about 300 μ

g and 1000 μ

g.

10. A method as in claim 8 wherein each said dose is between about 300 μ

g and 1000 μ

g.

11. A method as in claim 9 wherein at least the first dose is delivered in about 1 hour.

12. A method as in claim 10 wherein at least the first dose is delivered in about 1 hour.

13. A method as in claim 7 wherein said granisetron is contained in a hydrogel formulation.

14. A method as in claim 8 wherein said granisetron is contained in a hydrogel formulation.

15. A method as in claim 1 wherein said control system includes a control element comprising a sensor activated by an externally generated signal to initiate delivery of a dose of said therapeutic substance from a patch device previously applied to the body of a user.

18. A method as in claim 5 wherein said granisetron is in a form that can only be delivered by iontophoresis.

19. A method as in claim 7 wherein said control system provides steady low level delivery of about 40 μ

g/hr of granisetron after said first primary dose.

20. A method as in claim 1 wherein said donor reservoir contains a single source of reactive material.

21. A method as in claim 20 wherein said control circuit electronically controls dosage administration.

22. A method as in claim 1 wherein the amount of therapeutic substance supplied in the donor reservoir exceeds a desired total quantity to be delivered by the device to a user.

24. A method as in claim 2, wherein the content of reactive material at each donor electrode is such that depletion of the reactive material produces an open circuit condition with that electrode connected.

16. A method of administering granisetron to the body of a patient comprising:

(a) providing a disposable skin-worn patch device for the delivery of granisetron by iontophoresis, capable of providing a plurality of doses of granisetron to the body, comprising;

(1) a donor reservoir containing granisetron, said donor reservoir further including circuit elements configured to deliver a plurality of successive doses of granisetron by sequentially selectively connecting a plurality of separate sources of reactive material in said circuit in a manner such that each dose is delivered by a different source of reactive material;

(2) a counter reservoir;

(3) a source of electrical power; and

(4) a control system configured for controlling administration using a first completed circuit for supplying a primary dose of between about 300 μ

g and about 1000 μ

g of granisetron in a less than 2-hour time period upon application of the patch to the body surface, and user-operable device to allow user to self-administer sequentially an additional dose of between about 300 μ

g and about 1000 μ

g of granisetron;

(b) applying said device to the skin of a patient; and

(c) using said user operable device to administer an additional dose of granisetron when desired.

17. A method as in claim 16 wherein said granisetron is contained in a hydrogel formulation.

23. A disposable skin-worn device for the transdermal delivery of a plurality of doses of a charged therapeutic substance by iontophoresis comprising:

(a) a donor reservoir containing an amount of a therapeutic substance to be delivered transdermally by iontophoresis, said donor reservoir further including elements configured to deliver a plurality of successive doses of a therapeutic substance by sequentially selectively connecting a plurality of separate sources of reactive material in said circuit in a manner such that each dose is delivered by a different source of reactive material;

(b) a counter reservoir;

(c) a source of electric power connected in a circuit between said donor reservoir and said counter reservoir; and

(d) a user-operable control system configured to enable the plurality of successive doses of said therapeutic substance to be administered from said donor reservoir.

25. A method of providing transdermal delivery of a plurality of doses of a charged therapeutic substance to a patient, the method comprising:

(a) applying to a skin site of the patient a skin-worn device comprising;

(i) a donor reservoir containing an amount of a therapeutic substance to be delivered transdermally by iontophoresis, said donor reservoir further including circuit elements configured to deliver a plurality of successive doses of a therapeutic substance by sequentially selectively connecting a first and second electrode in a manner such that each dose is delivered by a different electrode;

(2) a counter reservoir;

(3) a source of electric power connected in a circuit between said donor reservoir and said counter reservoir; and

(4) a control system for controlling current flow in said circuit and configured to enable the plurality of successive doses of said therapeutic substance to be administered from said donor reservoir;

(b) controlling current flow in said circuit in a manner sufficient to iontophoretically deliver said therapeutic substance by said first electrode until said first electrode'"'"'s reactive species is depleted; and

(c) controlling current flow in said circuit in a manner sufficient to iontophoretically deliver said therapeutic substance by said second electrode.

26. The method as in claim 25, wherein the first and second electrodes are anodes and the reactive species is an oxidizable species.