Zero-order prolonged release coaxial implants

Abstract

A coaxial implant has been developed using entirely biodegradable polymeric materials. As referred to herein, a coaxial implant is a device having a core containing drug, surrounded by a semi-permeable membrane that controls the rate of release of material from the core. The device is formed by extrusion, using a pre-milling and extruding step to maximize uniformity of drug dispersion within the polymeric material. In one embodiment, the polymer is processed to yield a semi-crystalline polymer, rather than an amorphous polymer. The core containing the drug and the polymer membrane(s) can be the same or different polymer. The polymer can be the same or different composition (i.e., both polycaprolactone, or both poly(lactide-co-glycolide) of different monomer ratios, or polycaprolactone outside of a core of poly(lactide)), of the same or different molecular weights, and of the same or different chemical structure (i.e., crystalline, semi-crystalline or amorphous). The core acts as a reservoir of drug, which partitions from the core polymer to form a saturated solution of at least 10% drug at the polymer membrane.

1 - 36 . (canceled) 
     
     
         37 . A completely biodegradable coaxial implant, provided in the form of a rod and comprising a polymeric core containing active agent to be delivered and a polymeric rate-controlling membrane, wherein the polymeric core is formed from a polymer selected from the group consisting of polylactides, polyglycolides, polycaprolactones and copolymers thereof, and further wherein said implant does not degrade completely until all the active agent is released. 
     
     
         38 . The implant of  claim 37 , wherein the rate-controlling membrane is a microporous membrane. 
     
     
         39 . The implant of  claim 37 , wherein the rate-controlling membrane is a semi-permeable membrane. 
     
     
         40 . The implant of  claim 37 , wherein the polymeric core is formed by dry blending of active agent and polymer, followed by extrusion. 
     
     
         41 . The implant of  claim 37 , wherein the polymeric core is formed by a double extrusion process. 
     
     
         42 . The implant of  claim 37 , wherein the implant is formed using an extrusion process, and further processed after extrusion by drawing or annealing. 
     
     
         43 . The implant of  claim 37 , wherein the implant has sealed ends. 
     
     
         44 . The implant of  claim 37 , wherein said implant releases active agent with zero order release kinetics. 
     
     
         45 . The implant of  claim 37 , wherein the active agent is water soluble. 
     
     
         46 . The implant of  claim 37 , wherein the active agent is a protein or peptide. 
     
     
         47 . The implant of  claim 37 , wherein the polymeric rate-controlling membrane is formed from a polycaprolactone. 
     
     
         48 . A completely biodegradable coaxial implant, provided in the form of a rod and comprising a polymeric core containing active agent to be delivered and a polymeric rate-controlling membrane, wherein the rate-controlling membrane is formed from a polycaprolactone, and further wherein said implant does not degrade completely until all the active agent is released. 
     
     
         49 . The implant of  claim 48 , wherein the rate-controlling membrane is a microporous membrane. 
     
     
         50 . The implant of  claim 48 , wherein the rate-controlling membrane is a semi-permeable membrane. 
     
     
         51 . The implant of  claim 48 , wherein the polymeric core is formed by dry blending of active agent and polymer, followed by extrusion. 
     
     
         52 . The implant of  claim 48 , wherein the polymeric core is formed by a double extrusion process. 
     
     
         53 . The implant of  claim 48 , wherein the implant is formed using an extrusion process, and further processed after extrusion by drawing or annealing. 
     
     
         54 . The implant of  claim 48 , wherein the implant has sealed ends. 
     
     
         55 . The implant of  claim 48 , wherein said implant releases active agent with zero order release kinetics. 
     
     
         56 . The implant of  claim 48 , wherein the active agent is water soluble. 
     
     
         57 . The implant of  claim 48 , wherein the active agent is a protein or peptide. 
     
     
         58 . The implant of  claim 48 , wherein the polymeric core is formed from a polymer selected from the group consisting of polylactides, polyglycolides, polycaprolactones and copolymers thereof.