Polymeric devices for controlled release of active agents

Abstract

Polymeric devices for controlled release of an active agent of interest are provided. The active agent is provided within a biodegradable polymer system to supply a polymeric device for controlled release of the active agent. The polymer system is a copolymer or a polymer blend comprising a hydrophobic component and a hydrophilic component, and the polymer system does not form a hydrogel when contacted with, or immersed in an aqueous system, for example when the device is implanted in a subject. When the device is administered to a subject, for example, when it is implanted, the device releases the active agent in a controlled fashion without a lag period, or with a minimal lag period. Methods for producing the polymeric devices are also provided, as are methods of using the polymeric devices to provide for controlled release of an active agent in a subject.

1 . A polymeric device for controlled release of an active agent of interest, said device comprising 
 a biodegradable polymer system selected from the group consisting of copolymers and polymeric blends comprising a hydrophobic component and a hydrophilic component; and    an active agent, wherein the polymer system does not form a hydrogel when the device is contacted with an aqueous system, and further wherein the device releases the agent without a lag period or with a minimal lag period.    
     
     
         2 . The device of  claim 1  wherein the active agent is present in an amount up to 40 wt %.  
     
     
         3 . The device of  claim 1 , wherein the active agent is a peptide.  
     
     
         4 . The device of  claim 3 , wherein the peptide is a therapeutic and/or prophylactic peptide selected from the group consisting of hormones, growth factors, neuroactive agents, melanotropic peptides, cell adhesion factors, cytokines, and biological response modifiers.  
     
     
         5 . The device of  claim 4 , wherein the peptide is a GNRH molecule or a GnRH analog.  
     
     
         6 . The device of  claim 5 , wherein the GnRH analog is selected from the group consisting of desorelin, tryptorelin, goserelin, and leuprolide.  
     
     
         7 . The device of  claim 1 , wherein polymer system is a copolymer comprising a hydrophobic component and a hydrophilic component.  
     
     
         8 . The device of  claim 1 , wherein polymer system is a blend of a hydrophobic polymer and a hydrophilic polymer.  
     
     
         9 . The device of  claim 1 , wherein the hydrophilic component is present in an amount of up to 25%.  
     
     
         10 . The device of  claim 1 , wherein the hydrophilic component is present in an amount of up to 15%.  
     
     
         11 . The device of  claim 1 , wherein the hydrophilic component is present in an amount of between 0.5 and 10 weight percent.  
     
     
         12 . The device of  claim 1 , wherein the polymer system is an AB copolymer wherein the A component is a copolymer of lactide, glycolide, or caprolactone, and the B component is a polyalkyleneglycol.  
     
     
         13 . The device of  claim 11 , wherein the B component is a polyalkyleneglycol at 1.25 weight percent and the hydrophobic polymer is poly(lactide-co-glycolide).  
     
     
         14 . The device of  claim 1 , wherein the active agent is distributed uniformly within the polymer.  
     
     
         15 . The device of  claim 1 , wherein the active agent is incorporated using a non-solvent process.  
     
     
         16 . The device of  claim 1 , wherein the device is formed by dry melt extrusion.  
     
     
         17 . The device of  claim 1 , wherein the device is formed by melt extrusion of the copolymer mixed with peptide.  
     
     
         18 . The device of  claim 1 , wherein the active agent is released with linear or near zero order release kinetics.  
     
     
         19 . The device of  claim 1 , wherein the polymer system comprises greater than 75 wt % hydrophobic polymer.  
     
     
         20 . The device of  claim 19 , wherein the polymer system comprises greater than 85 wt % hydrophobic polymer.  
     
     
         21 . The device of  claim 20 , wherein the polymer system comprises greater than 91 wt % hydrophobic polymer.  
     
     
         22 . The device of  claim 21 , wherein the polymer system comprises greater than 98 wt % hydrophobic polymer.  
     
     
         23 . The device of  claim 1 , wherein the hydrophobic component of the polymer system is selected from the group consisting of polyhydroxy acids, such as poly(lactide)s, poly(glycolide)s, poly(lactide-co-glycolide)s, poly(lactic acid)s, poly(glycolic acid)s, and poly(lactic acid-co-glycolic acid)s, polyanhydrides, polyorthoesters, polyetheresters, polycaprolactone, polyesteramides, polyphosphazines, polycarbonates, polyamides, and copolymers thereof.  
     
     
         24 . The device of  claim 1 , wherein the hydrophilic component of the polymer system is polyethylene glycol.  
     
     
         25 . The device of  claim 1  provided in the form of a fiber, needle or rod.  
     
     
         26 . The device of  claim 1  provided in the form of a sheet, film or coating.  
     
     
         27 . The device of  claim 1  provided in microparticulate form.  
     
     
         28 . The device of  claim 1  free of solvent residue.  
     
     
         29 . The device of  claim 1  for treating disease wherein the active agent is a GnRH molecule or a GnRH analogue.  
     
     
         30 . The device of  claim 1 , wherein the active agent is a GnRH molecule or a GnRH analogue used for lowering gonadotropin levels.  
     
     
         31 . A method of making the device of  claim 1 , said method comprising mixing the polymer system and the active agent, extruding the mixture of the polymer system and active agent, grinding or milling the extruded mixture, and feeding the ground or milled extruded mixture into an extruder to produce a solid implant.