Method and device for transdermal electrotransport delivery of fentanyl and sufentanil

• US 6,171,294 B1
• Filed: 07/10/1997
• Issued: 01/09/2001
• Est. Priority Date: 06/05/1995
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Southam, Mary, Noorduin, Henk, Bernstein, Keith J.
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/890,966
• Time in Patent Office: 1,279 Days
• Field of Search: 604/20-21, 604/501, 607/115, 424/448-449
• US Class Current: 604/501
• 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
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The invention provides an improved electrotransport drug delivery system for analgesic drugs, namely fentanyl and sufentanil. The fentanyl/sufentanil is provided as a water soluble salt (eg, fentanyl hydrochloride) dispersed in a hydrogel formulation for use in an electrotransport device (10). In accordance with one aspect of the invention, the concentration of fentanyl/sufentanil in the donor reservoir (26) solution is above a predetermined minimum concentration, whereby the transdermal electrotransport flux of fentanyl/sufentanil is maintained independent of the concentration of fentanyl/sufentanil in solution. In accordance with a second aspect of the present invention, the donor reservoir (26) of the electrotransport delivery device (10) is comprised of silver and the donor reservoir (26) contains a predetermined “excess” loading of fentanyl/sufentanil halide to prevent silver ion migration with attendant skin discoloration. In accordance with a third aspect of the present invention, a transdermal electrotransport delivered dose of fentanyl/sufentanil is provided which is sufficient to induce analgesia in (eg, adult) human patients suffering from moderate-to-severe pain associated with major surgical procedures.

Claims

1. A method of obtaining self-administered analgesia in a human patient who is suffering from pain consisting of transdermally delivering solely by electrotransport a dose of about 20 μ

g to about 60 μ

g of fentanyl over a predetermined delivery period of up to about 20 minutes from an electrotransport device which includes a donor reservoir hydrogel formulation comprised of fentanyl, terminating said delivery at the end of said delivery period and allowing the patient to self-administer from about 10 to about 100 additional of said doses over a period of 24 hours.

2. The method of claim 1, wherein about 35 μ

g to about 45 μ

g of fentanyl is delivered over a delivery period of about 5 to 15 minutes.

3. The method of claim 1, wherein about 40 μ

g of fentanyl is delivered over the delivery period.

4. The method of claim 1, wherein the delivery period is about 10 minutes.

5. The method of claim 1, wherein the additional doses are 35 μ

g to 45 μ

g doses of fentanyl.

6. The method of claim 1, wherein the donor reservoir formulation comprising a fentanyl salt is placed in contact with the body surface.

7. The method of claim 6, wherein the fentanyl salt comprises about 1.9 to 2.0 wt % of the formulation.

8. The method of claim 7, wherein the fentanyl salt is fentanyl hydrochloride.

9. The method of claim 6, wherein the donor reservoir formulation comprises polyvinyl alcohol.

19. The method of claim 1 wherein no more than six doses per hour are delivered by the device.

10. A method of obtaining self-administered analgesia in a human patient who is suffering from pain consisting of transdermally delivering solely by electrotransport a dose of about 2.3 μ

g to about 7.0 μ

g of sufentanil over a predetermined delivery period of up to about 20 minutes from an electrotransport device which includes a donor reservoir hydrogel formulation comprised of sufentanil, terminating said delivery at the end of said delivery period and allowing the patient to self-administer from about 10 to about 100 additional of said doses over a period of 24 hours.

11. The method of claim 10, wherein about 4 μ

g to about 5.5 μ

g of sufentanil is delivered over a delivery period of about 5 to 15 minutes.

12. The method of claim 10, wherein about 4.7 μ

g of sufentanil is delivered over the delivery period.

13. The method of claim 10, wherein the delivery period is about 10 minutes.

14. The method of claim 10, wherein the additional doses are 4 μ

g to 5.5 μ

g doses of sufentanil.

15. The method of claim 10, wherein the donor reservoir formulation comprising a sufentanil salt is placed in contact with the body surface.

16. The method of claim 10, wherein the sufentanil salt comprises about 1.9 to 2.0 wt % of the formulation.

17. The method of claim 16, wherein the sufentanil salt is sufentanil hydrochloride.

18. The method of claim 10, wherein the donor reservoir formulation comprises polyvinyl alcohol.

20. The method of claim 10 wherein no more than six doses per hour are delivered by the device.