Method and device for transdermal delivery of fentanyl and sufentanil

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.

Description

TECHNICAL FIELD [0001] The invention relates generally to improved electrotransport drug delivery. Specifically, the invention relates to a device, composition and method for improved electrotransport delivery of analgesic drugs, particularly fentanyl and analogs of fentanyl. A composition is provided in the form of a hydrogel formulation for use in an electrotransport device. BACKGROUND ART [0002] The transdermal delivery of drugs, by diffusion through the epidermis, offers improvements over more traditional delivery methods, such as subcutaneous injections and oral delivery. Transdermal drug delivery avoids the hepatic first pass effect encountered with oral drug delivery. Transdermal drug delivery also eliminates patient discomfort associated with subcutaneous injections. In addition, transdermal delivery can provide more uniform concentrations of drug in the bloodstream of the patient over time due to the extended controlled delivery profiles of certain types of transdermal deli...

AI Technical Summary

Benefits of technology

[0017] The present invention provides a method for improved transdermal electrotransport delivery of fentanyl and analogs of fentanyl, particularly sufentanil. As such, the method of the present invention provides a greater degree of efficiency in electrotransport delivery of analgesic fentanyl or sufentanil, concomitantly providing a greater measure of patient safety and comfort in pain management. The foregoing, and other advantages of the present invention, are provided by a method of delivering fentanyl or sufentanil through a body surface (eg, intact skin) by electrotransport from an electrotransport delivery device having a anodic donor reservoir containing an at least partially aqueous solution of a fentanyl / sufentanil salt.

[0019] For sufentanil, the transdermal electrotransport flux remains independent of sufentanil concentration at or above about 1.7 mM substantially throughout the sufentanil electrotransport delivery period. By maintaining the concentration of sufentanill salt solution at or above about 1.7 mM in the donor reservoir, the electrotransport flux of the drug remains substantially independent of the drug concentration in the donor reservoir solution and substantially proportional to the level of electrotransport current applied by the delivery device during the electrotransport drug delivery. Maintaining the sufentanil salt solution concentration above about 1.7 mM ensures a predictable sufentanil flux with a particular applied electrotransport current.

[0021] In yet another aspect, the present invention concerns a method of administering fentanyl or sufenanil by transdermal electrotransport in order to treat moderate-to-severe pain associated with major surgical procedures. We have determined that a transdermal electrotransport dose of about 20 μg to about 60 μg of fentanyl, delivered over a delivery interval of up to about 20 minutes, is therapeutically effective in treating moderate-to-severe post-operative pain in human patients having body weights above about 35 kg. Preferably, the amount of fentanyl delivered is about 35 μg to about 45 μg over a delivery interval of about 5 to 15 minutes, and most preferably the amount of fentanyl delivered is about 40 μg over a delivery interval of about 10 minutes. Since fentanyl has a relatively short distribution half life once delivered into a human body (ie, about 3 hours), the method of inducing analgesia preferably includes a method for maintaining the analgesia so induced. Thus the method of transdermally delivering fentanyl by electrotransport preferably includes delivering at least 1 additional, more preferably about 10 to 100 additional, and most preferably about 20 to 80 additional, like dose(s) of fentanyl over subsequent like delivery interval(s) over a 24 hour period. The ability to deliver multiple identical doses from a transdermal electrotransport fentanyl delivery device also provides the capability of pain management to a wider patient population, in which different patients require different amounts of fentanyl to control their pain. By providing the capability of administering multiple small transdermal electrotransport fentanyl doses, the patients can titrate themselves to administer only that amount of fentanyl which is needed to contol their pain, and no more.

Problems solved by technology

The wire connections are subject to disconnection and limit the patient's movement and mobility.

Wires between electrodes and controls may also be annoying or uncomfortable to the patient.

Due to their bulk and complexity, commercially available PCA devices generally require the patient to be confined to a bed, or some other essentially fixed location.

Thus, as practiced using commercially available PCA devices, PCA requires the presence of highly skilled medical technicians to initiate and supervise the operation of the PCA device along with its attendant risk of infection.

Further, commercially available PCA devices themselves are somewhat painful to use by virtue of their percutaneous (ie, intravenous or subcutaneous) access.

Further, little progress has been made to provide a hydrogel formulation for analgesic electrotransport, particularly fentanyl transdermal electrotransport delivery, that has long term stability and has performance characteristics comparable to the patient controlled electromechanical pumps for, eg, intravenous delivery of analgesic.

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