Implantable Devices and Methods for Treatment of Pain by Delivery of Fentanyl and Fentanyl Congeners

Abstract

The invention features devices and methods for treatment of pain. The drug delivery device is a drug delivery system adapted for whole implantation in a subject and to provide pain relief by delivery of fentanyl or a fentanyl congener (e.g., sufentanil) over a protracted period of time (e.g., at least 3 days or more than 3 days). The device comprises a housing defining a reservoir that contains a drug formulation, a pump operatively connected to the housing so as to facilitate movement of drug out of the reservoir and out of the device, and a thermal expansion element which defines a flow pathway comprising a thermal expansion channel to accommodate thermal expansion of formulation in the reservoir. The device can further comprise a valve positioned within the flow pathway so as to prevent movement of drug out of the reservoir prior to use.

1 . A controlled drug delivery device, adapted for whole implantation, the device comprising:
 a housing defining a reservoir, the reservoir containing a formulation comprising a drug selected from the group consisting of fentanyl or a fentanyl congener, wherein the drug is present in an amount sufficient for treatment of pain in a subject for a period of at least about 3 days;   a pump operatively connected to the housing; and   a thermal expansion element comprising an inlet, a thermal expansion channel adapted to contain a volume of formulation associated with thermal expansion, and an outlet;   wherein in use, the inlet, thermal expansion channel, and outlet define a flow pathway from the reservoir and out of the device such that actuation of the pump effects movement of formulation through the flow pathway.   
     
     
         2 . The device of  claim 1 , wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing. 
     
     
         3 . The device of  claim 1 , wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing, and an inner wall of the housing. 
     
     
         4 . The device of  claim 1 , wherein the thermal expansion element comprises a valve positioned and adapted for maintaining a sealed reservoir until opened. 
     
     
         5 . The device of  claim 4 , wherein the thermal expansion element comprises a plunger, wherein at least a portion of the plunger is slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation out of the outlet. 
     
     
         6 . The device of  claim 1 , wherein the flow pathway narrows from a wider inlet and thermal expansion channel to a narrower outlet. 
     
     
         7 . The device of  claim 1 , wherein the device is adapted for delivery of drug at a rate of from about 0.01 micrograms per hour to 2000 micrograms per hour. 
     
     
         8 . The device of  claim 1 , wherein said drug is present in a concentration of about 5 mg/mL to about 400 mg/mL. 
     
     
         9 . The device of  claim 1 , wherein the drug is sufentanil. 
     
     
         10 . A method of treating pain in a subject, the method comprising the steps of:
 wholly implanting at an implantation site in a subject the drug delivery device of  claim 1 ; and   parenterally delivering the formulation from the drug delivery device to the subject so that drug enters the systemic circulation and is transported thereby to a site of action in an amount sufficient to treat pain.   
     
     
         11 . The method of  claim 10 , wherein the thermal expansion element of the device comprises a valve and a plunger, at least a portion of the plunger being slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation past the thermal expansion channel in a direction toward the outlet, and wherein the method further comprises the step of actuating the plunger so as to open the valve prior to said implanting. 
     
     
         12 . The method of  claim 10 , wherein the drug delivery device is implanted at a subcutaneous site. 
     
     
         13 . The method of  claim 10 , wherein the formulation is delivered at a volume rate of from about 0.01 μl/day to 2 ml/day 
     
     
         14 . The method of  claim 10 , wherein drug is delivered at a rate of from about 0.01 μg per hour to 2,000 μg per hour. 
     
     
         15 . The method of  claim 10 , wherein the drug is sufentanil. 
     
     
         16 . The method of  claim 10 , wherein said delivering is for a period of from about 4 weeks to 12 months. 
     
     
         17 . The method of  claim 10 , wherein the device comprises an amount of drug sufficient to provide for alleviation of pain in the subject for a period of more than 30 days. 
     
     
         18 . A controlled drug delivery device, adapted for whole implantation, the device comprising:
 a housing defining a reservoir, the reservoir containing a formulation comprising sufentanil in an amount sufficient for treatment of pain in a subject for a period of at least about 3 days;   a pump operatively connected to the housing; and   a thermal expansion element comprising an inlet, a thermal expansion channel adapted to contain a volume of formulation associated with thermal expansion, and a delivery outlet;   wherein in use, the inlet, thermal expansion channel, and outlet define a flow pathway from the reservoir and out of the device such that actuation of the pump effects movement of formulation through the flow pathway.   
     
     
         19 . The device of  claim 18 , wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing. 
     
     
         20 . The device of  claim 18 , wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing, and an inner wall of the housing. 
     
     
         21 . The device of  claim 18 , wherein the thermal expansion element comprises a valve. 
     
     
         22 . The device of  claim 18 , wherein the thermal expansion element comprises a plunger, wherein at least a portion of the plunger is slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation through the outlet. 
     
     
         23 . The device of  claim 18 , wherein said drug is present in a concentration of about 50 mg/mL to about 400 mg/mL. 
     
     
         24 . A method of treating pain in a subject, the method comprising the steps of:
 wholly implanting at an implantation site in a subject the drug delivery device of  claim 18 ; and   parenterally delivering the formulation from the drug delivery device to the subject so that drug enters the systemic circulation and is transported thereby to a site of action in an amount sufficient to treat pain.   
     
     
         25 . The method of  claim 23 , wherein the drug delivery device is implanted at a subcutaneous site. 
     
     
         26 . The method of  claim 23 , wherein the formulation is delivered at a volume rate of from about 0.01 μl/day to 2 ml/day 
     
     
         27 . The method of  claim 23 , wherein the device comprises an amount of drug sufficient to provide for alleviation of pain in the subject for a period of more than 30 days.