Implantable polymeric device for sustained release of buprenorphine

Abstract

The present invention provides compositions, methods, and kits for treatment of opiate addiction and pain. The invention provides a biocompatible nonerodible polymeric device which releases buprenorphine continuously with generally linear release kinetics for extended periods of time. Buprenorphine is released through pores that open to the surface of the polymeric matrix in which it is encapsulated. The device may be administered subcutaneously to an individual in need of continuous treatment with buprenorphine.

1 - 36 . (canceled)  
     
     
         37 . An implantable device for treating opiate addiction, comprising buprenorphine and a biocompatible, nonerodible polymer, wherein said device comprises a polymeric matrix comprising buprenorphine blended with said polymer, and wherein when said implantable device is implanted subcutaneously in a mammal, said buprenorphine is continuously released in vivo over a sustained period of time through pores that open to the surface of said matrix at a rate that results in a steady state plasma buprenorphine level of at least about 0.1 ng/ml, wherein said device is washed with ethanol prior to subcutaneous implantation, wherein said device does not comprise a coating that is impermeable to buprenorphine, wherein said device does not comprise external medical equipment, and wherein said washing with ethanol removes surface buprenorphine and reduces the initial burst of buprenorphine released in vivo after subcutaneous implantation relative to an unwashed device.  
     
     
         38 . An implantable device according to  claim 37 , wherein the polymeric matrix comprises ethylene vinyl acetate copolymer (EVA).  
     
     
         39 . An implantable device according to  claim 38 , wherein said EVA comprises about 33% vinyl acetate.  
     
     
         40 . An implantable device according to  claim 39 , comprising about 10 to about 85% buprenorphine.  
     
     
         41 . An implantable device according to  claim 40 , comprising about 50% buprenorphine.  
     
     
         42 . An implantable device according to  claim 40 , comprising about 75% buprenorphine.  
     
     
         43 . An implantable device according to  claim 39 , wherein the implantable device is produced by an extrusion process.  
     
     
         44 . An implantable device according to  claim 43 , comprising dimensions of about 1.5 to about 5 mm in diameter and about 0.5 to about 7 cm in length.  
     
     
         45 . An implantable device according to  claim 44 , comprising dimensions of about 2.4 mm in diameter and about 2.6 cm in length.  
     
     
         46 . An implantable device according to  claim 45 , wherein said implantable device releases about 1 mg buprenorphine per day in vitro.  
     
     
         47 . An implantable device according to  claim 46 , wherein the sustained period of time is at least about 3 months.  
     
     
         48 . An implantable device for treating pain, comprising buprenorphine and a biocompatible, nonerodible polymer, wherein said device comprises a polymeric matrix comprising buprenorphine blended with said polymer, and wherein when said implantable device is subcutaneously implanted in a mammal, said buprenorphine is continuously released in vivo over a sustained period of time through pores that open to the surface of said matrix at a steady state rate of at least about 0.1 mg per day, wherein said device is washed with ethanol prior to subcutaneous implantation, wherein said device does not comprise a coating that is impermeable to buprenorphine, wherein said device does not comprise external medical equipment, and wherein said washing with ethanol removes surface buprenorphine and reduces the initial burst of buprenorphine released in vivo after subcutaneous implantation relative to an unwashed device.  
     
     
         49 . An implantable device according to  claim 48 , wherein the polymeric matrix comprises EVA.  
     
     
         50 . An implantable device according to  claim 49 , wherein said EVA comprises 33% vinyl acetate.  
     
     
         51 . An implantable device according to  claim 50 , comprising about 10 to about 85% buprenorphine.  
     
     
         52 . An implantable device according to  claim 51 , comprising about 50% buprenorphine.  
     
     
         53 . An implantable device according to  claim 51 , comprising about 75% buprenorphine.  
     
     
         54 . An implantable device according to  claim 50 , wherein the implantable device is produced by an extrusion process.  
     
     
         55 . An implantable device according to  claim 54 , comprising dimensions of about 1.5 to about 5 mm in diameter and about 0.5 to about 7 cm in length.  
     
     
         56 . An implantable device according to  claim 55 , comprising dimensions of about 2.4 mm in diameter and about 2.6 cm in length.  
     
     
         57 . An implantable device according to  claim 56 , wherein said implantable device releases about 1 mg buprenorphine per day in vitro.  
     
     
         58 . An implantable device according to  claim 57 , wherein the sustained period of time is at least about 3 months.  
     
     
         59 . A kit for use in treatment of opiate addiction, comprising at least one implantable device according to  claim 37 , and instructions for use.  
     
     
         60 . A kit for use in treatment of pain, comprising at least one implantable device according to  claim 48 , and instructions for use.  
     
     
         61 . An implantable device according to  claim 37 , wherein said device is washed in ethanol for 30 minutes  
     
     
         62 . An implantable device according to  claim 48 , wherein said device is washed in ethanol for 30 minutes.  
     
     
         63 . A process for producing a subcutaneously implantable device comprising buprenorphine and a biocompatible, nonerodible polymeric matrix, said process comprising washing said device in a solution in which buprenorphine is soluble, wherein the initial burst of buprenorphine released in vivo after subcutaneous implantation is reduced relative to an unwashed device.  
     
     
         64 . A process according to  claim 63 , wherein said device is washed in ethanol.  
     
     
         65 . A process according to  claim 64 , wherein said device is washed in ethanol for 30 minutes.  
     
     
         66 . A delivery system for treatment of opiate addiction, comprising a multiplicity of implantable devices according to  claim 37 , wherein when said multiplicity of devices is implanted subcutaneously in a mammal, buprenorphine is continuously released in vivo at a rate that results in a therapeutically effective steady state plasma level for treatment of opiate addiction.  
     
     
         67 . A delivery system for treatment of pain, comprising a multiplicity of implantable devices according to  claim 48 , wherein when said multiplicity of devices is implanted subcutaneously in a mammal, buprenorphine is continuously released in vivo at a rate that results in an analgesically effective steady state rate for treatment of pain.  
     
     
         68 . A kit for use in treatment of opiate addiction, comprising a delivery system according to  claim 66 .  
     
     
         69 . A kit for use in treatment of pain, comprising a delivery system according to  claim 67.