Method and device for transdermal electrotransport 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.

1 - 23 . (canceled)  
     
     
         24 . An electrotransport device for drug delivery through a body surface comprising: silver anodic donor electrode, cathodic counter electrode, and a donor reservoir containing a loading amount of analgesic drug in electrical contact with the donor electrode, the analgesic being a salt of an agent selected from the group consisting of fentanyl and fentanyl analog, and electronic circuit controlling delivery of the analgesic drug, the device adapted to deliver a predetermined maximum total amount of the analgesic drug over a period of time, the loading amount being at least about two times greater than the predetermined maximum total amount.  
     
     
         25 . The device of  claim 24 , wherein the donor reservoir comprises a hydrogel containing an aqueous analgesic drug solution of a fentanyl salt selected from the group consisting of fentanyl halide salts and sufentanil halide salts in a loading that is at least 3 times greater than the predetermined maximum total amount to prevent transient epidermal discoloration, and wherein the donor reservoir is substantially free of sources of halide other than the selected analgesic drug halide salt.  
     
     
         26 . The device of  claim 24 , wherein the donor reservoir comprises a hydrogel containing an aqueous fentanyl salt solution in a loading that is at least 3 times greater than the predetermined maximum total amount, and such that after delivery of the predetermined maximum total amount the fentanyl concentration is still above 6 mg/mL in the hydrogel, the body surface is skin.  
     
     
         27 . The device of  claim 24 , wherein the donor reservoir comprises a hydrogel containing an aqueous fentanyl salt solution or a sufentanil salt solution and the body surface is intact human skin and the period of time is at least 6 hours.  
     
     
         28 . The device of  claim 24 , wherein the electronic circuit enables the delivery of the analgesic drug through the body surface only up to predetermined maximum total amount of the analgesic drug and wherein the drug delivery is substantially proportional to a level of current applied by the delivery device during the iontophoretic drug delivery.  
     
     
         29 . The device of  claim 24 , wherein the drug is a salt of fentanyl or salt of sufentanil and the electronic circuit enables electrotransport current between about 150 μA to about 240 μA.  
     
     
         30 . The device of  claim 28 , wherein the drug is a salt of fentanyl or salt of sufentanil and the electronic circuit enables electrotransport current between about 150 μA to about 190 μA.  
     
     
         31 . The device of  claim 28 , wherein the drug is a salt of fentanyl or salt of sufentanil and the electronic circuit enables electrotransport current between about 190 μA to about 240 μA.  
     
     
         32 . The device of  claim 24 , wherein the device is adapted to deliver only up to the predetermined maximum total amount of the analgesic drug in multiple predetermined dose amounts.  
     
     
         33 . The device of  claim 32 , wherein the electronic circuit enables electrotransport current for a delivery interval of up to about 20 minutes.  
     
     
         34 . The device of  claim 32 , wherein the electronic circuit enables electrotransport current for a delivery interval of about 8 to about 12 minutes.  
     
     
         35 . The device of  claim 32 , wherein the device is adapted to deliver about 10 to about 100 dose amounts.  
     
     
         36 . The device of  claim 32 , wherein the device is adapted to deliver about 20 to about 80 dose amounts.  
     
     
         37 . The device of  claim 36 , wherein the predetermined dose amount is about 20 to 60 μg fentanyl halide.  
     
     
         38 . The device of  claim 37 , wherein the predetermined dose amount is about 40 μg fentanyl halide.  
     
     
         39 . The device of  claim 32 , wherein the device is adapted to deliver multiple predetermined dose amounts over at least about 6 hours.  
     
     
         40 . The device of  claim 24 , wherein the analgesic drug comprises sufentanil hydrochloride and the loading amount is at least about 4 times greater than the predetermined maximum total amount.  
     
     
         41 . The device of  claim 24 , wherein the donor reservoir has a weight on a hydrated basis of about 0.5 g to 0.8 g and is loaded with at least about 9 mg of fentanyl hydrochloride.  
     
     
         42 . The device of  claim 24 , further comprising the device is adapted to deliver the drug up to the predetermined maximum total amount while maintaining the amount of analgesic drug in the drug reservoir at least equal to twice the predetermined maximum total amount of the analgesic drug.  
     
     
         43 . An electrotransport device for drug delivery through a body surface comprising: silver anodic donor electrode, cathodic counter electrode, donor reservoir containing a loading amount of the analgesic drug in electrical contact with the donor electrode, and electronic circuit controlling delivery of the analgesic drug, wherein the donor reservoir comprises a hydrogel containing an aqueous fentanyl salt solution that has a weight on a hydrated basis of about 0.5 g to 0.8 g, is loaded with at least about 9 mg of fentanyl hydrochloride and is substantially free of sources of halide other than the fentanyl hydrochloride, the device adapted to deliver a predetermined maximum total amount of analgesic drug over a period of time, the loading amount being at least two times greater than the predetermined maximum total amount to prevent transient epidermal discoloration by silver, the electronic circuit enabling the delivery of the predetermined maximum total amount of the analgesic drug by delivering about 10 to about 100 predetermined dose amounts, wherein the predetermined dose amount comprises about 20 to 60 μg fentanyl halide, the electronic circuit enabling the application of an electrotransport current of about 150 μA to about 240 μA for a delivery interval of about 8 to about 12 minutes; such that fentanyl concentration in the hydrogel is above 6 mg/mL in the hydrogel even after delivery of the predetermined maximum total amount of the analgesic drug.  
     
     
         44 . An electrotransport device for drug delivery through a body surface comprising: silver anodic donor electrode, cathodic counter electrode, donor reservoir containing a loading amount of the analgesic drug in electrical contact with the donor electrode, and electronic circuit effecting delivery of the analgesic drug, wherein the donor reservoir comprises a hydrogel containing an aqueous sufentanil salt solution, the device adapted to deliver a predetermined maximum total amount of analgesic drug over a period of time, the loading amount being at least about two times greater than the predetermined maximum total amount, the electronic circuit enabling the delivery of only up to the predetermined maximum total amount of the analgesic drug by delivering about 10 to about 100 predetermined dose amounts, wherein the predetermined dose amount comprises about 4 to 5.5 μg sufentanil halide delivered by applying a current of about 150 μA to about 240 μA for a delivery interval of up to about 20 minutes; wherein the drug reservoir prior to delivery has a loading amount of the analgesic drug that is at least about four times greater than the predetermined maximum total amount to prevent transient epidermal discoloration.