Transdermal delivery device

• US 5,464,387 A
• Filed: 10/27/1994
• Issued: 11/07/1995
• Est. Priority Date: 07/24/1991
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Gyory, J. Richard, Theeuwes, Felix, Lattin, Gary A., Haak, Ronald P.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): SMITH, CHALIN A
• Application Number:
  US08/330,031
• Time in Patent Office: 376 Days
• Field of Search: 604/890.1, 604/891.1, 604/20, 604/26, 604/49, 128/898, 128/798, 128/799, 128/802, 128/803
• US Class Current: 604/20
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61K 9/7092 Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• 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

Abstract

A transdermal drug delivery device (20) is provided having both an active drug reservoir (24) and a passive drug reservoir (26). Drug is actively delivered by iontophoresis from the active drug reservoir (24) by an electric field generated by a power source (21). Simultaneously, drug is delivered from passive reservoir (26) by passive (i.e., non-electrically assisted) diffusion. In one embodiment, the passive drug reservoir (26) is electrically insulated from the active drug reservoir (24). In a second embodiment, both the active and the passive drug are contained in the same reservoir (34). In the second embodiment, the active drug is ionizable while the passive drug is non-ionizable. Most preferably, the active drug is an ionizable form (i.e., a salt form) of the passive drug.

Claims

1. A transdermal agent delivery device, comprising:

an agent reservoir adapted to be placed in agent transmitting relation with a body surface and positioned within an electric field generated by electrically connecting the agent reservoir to a source of electrical power, the agent reservoir containing;

a sufficient amount of a passively transported agent to achieve a therapeutically effective passive flux of the passive agent from the reservoir to, and through, a body surface when the reservoir is placed in passive agent transmitting relation with the body surface; and

a sufficient amount of an actively transported agent to achieve a therapeutically effective electrically assisted flux of the active agent from the reservoir to, and through, a body surface when the reservoir is placed in active agent transmitting relation with the body surface and an electric field is generated through said reservoir.

2. The device of claim 1, wherein the active agent is ionized and the passive agent is nonionized.

3. The device of claim 1, including means for electrically connecting and electrically disconnecting the power source and the agent reservoir.

4. The device of claim 3, wherein the means for electrically connecting and electrically disconnecting comprises an on-off switch.

5. The device of claim 2, wherein the ionized actively transported agent comprises an aqueous salt solution.

6. The device of claim 2, wherein the actively transported agent comprises an ionized form of the passively transported nonionized agent.

7. The device of claim 1, wherein the passively transported agent is an acid or a base and the actively transported agent is a salt of the acid or base.

8. The device of claim 1, wherein the actively transported agent and the passively transported agent are narcotic analgesics.

9. The device of claim 1, wherein the active agent reservoir is comprised at least in part of a hydrophilic polymer matrix containing the active agent.

10. The device of claim 1, wherein the agent reservoir comprises a donor reservoir of an iontophoretic delivery device.

11. The device of claim 1, wherein the agent reservoir comprises the donor and counter reservoirs of an iontophoretic delivery device.

12. The device of claim 11, wherein the counter reservoir is substantially free of the actively transported agent.

13. A method of delivering an agent transdermally comprising:

a) placing a reservoir containing a sufficient amount of an actively transported agent to achieve a therapeutically effective electrically assisted flux of the active agent from the reservoir to, and through, a body surface when the reservoir is placed in active agent transmitting relation with a body surface;

b) placing a reservoir containing a passively transported agent to achieve a therapeutically effective passive flux of the passive agent from the reservoir to, and through, a body surface when the reservoir is placed in passive agent transmitting relation with a body surface to passively transport said passive agent through the body surface; and

c) generating an electric field at least through the reservoir containing the actively transported agent to actively transport said agent through the body surface.

14. The method of claim 13, including periodically deactivating the electric field to stop the active transport of the active agent.

15. The method of claim 13, wherein the active agent is ionized and the passive agent is nonionized.

16. The method of claim 13, wherein the active agent comprises an aqueous salt solution.

17. The method of claim 13, wherein the active agent comprises a salt of the passive agent.

18. The method of claim 13, wherein the passive agent is an acid or a base and the active agent is a salt of the acid or base.

19. A method of treating chronic pain characterized by periodic episodes of more severe pain, comprising:

a) placing in a reservoir a sufficient amount of a nonionized narcotic analgesic to achieve a chronic pain reducing passive flux of the nonionized narcotic analgesic through a body surface of a patient when the reservoir is placed in narcotic analgesic transmitting relation with the body surface;

b) placing in the reservoir a sufficient amount of an ionized narcotic analgesic to achieve a severe pain reducing combined flux of the narcotic analgesics, the combined flux being comprised of an electrically assisted flux of the ionized narcotic analgesic and a passive flux of the nonionized narcotic analgesic;

c) generating an electric field through the reservoir when the patient experiences an episode of severe pain.

20. The method of claim 19, wherein the ionized narcotic analgesic comprises a salt of fentanyl or sufentanil.

21. The method of claim 19, wherein the nonionized narcotic analgesic comprises fentanyl base or sufentanil base.

22. A method of delivering an ionized actively transported agent and a nonionized passively transported agent through a body surface of a patient, comprising:

a) placing an amount of the nonionized passively transported agent in a reservoir, the amount of nonionized agent being sufficient to achieve a therapeutic passive flux of the nonionized agent from the reservoir to, and through, the body surface when the reservoir is placed in agent transmitting relation with the body surface;

b) placing an amount of the ionized actively transported agent in the reservoir, the amount of ionized agent being sufficient to achieve a therapeutic electrically assisted flux of the ionized agent from the reservoir to, and through, the body surface when the reservoir is placed in agent transmitting relation with the body surface and an electric field is generated through the reservoir;

c) placing the reservoir in agent transmitting relation with the body surface to passively transport said nonionized agent through the body surface at a therapeutic passive flux; and

d) generating an electric field through the body surface at a therapeutic electrically assisted flux.

23. The method of claim 22, including periodically generating the electric field.

24. The method of claim 22, wherein the ionized agent comprises an aqueous salt solution.

25. The method of claim 22, wherein the ionized agent comprises a salt of the nonionized agent.

26. The method of claim 22, wherein the nonionized agent is an acid or a base and the ionized agent is a salt of the acid or base.