Low temperature drying methods for forming drug-containing polymeric compositions

Abstract

The present invention relates to a process for reducing solvent contents in drug-containing polymeric compositions. Specifically, the solvent contents in the drug-containing polymeric compositions are first reduced by one or more conventional drying methods, to a range from about 0.5 wt % to about 10 wt % of the total weight of the polymeric composition. Subsequently, the drug-containing polymeric compositions are further treated by one or more low temperature (i.e., having processing temperatures of less than 60° C.) drying methods for further reduction of the solvent content to less than 10,000 ppm.

What is claimed is: 
     
         1 . An implantable medical device made by a method comprising:
 providing an implantable medical device;   forming a drug-containing polymeric composition comprising a biocompatible polymeric matrix with one or more therapeutic agents, wherein said polymeric matrix further comprises one or more organic or aqueous solvents, the polymeric matrix comprising at least two polymers;   oven drying the drug-containing polymeric composition for first period of time so as to reduce solvent content in the polymeric matrix;   subsequently removing additional solvents from the drug-containing polymeric composition after oven drying the composition utilizing a supercritical carbon dioxide process to reduce solvent content in the polymeric matrix to an amount less than about 10,000 ppm of the polymeric matrix, wherein the first period of time is at least six hours to reduce porosity in the drug-containing polymeric composition during the supercritical carbon dioxide process; and   coating at least a portion of the implantable drug device with the drug-containing composition.   
     
     
         2 . The implantable medical device of  claim 1 , wherein the drug-containing polymeric composition comprises a polymeric blend containing a first, stiffer biocompatible polymer and a second, softer biocompatible polymer. 
     
     
         3 . The implantable medical device of  claim 1 , wherein the drug-containing polymeric composition comprises a polymer and a plasticizer. 
     
     
         4 . The implantable medical device of  claim 1 , wherein the super-critical drying process is carried out by using supercritical carbon dioxide at a temperature ranging from about 25° C. to about 50° C. and a pressure ranging from about 10 bars to about 500 bars. 
     
     
         5 . The implantable medical device of  claim 4 , wherein the solvent content in the drug-containing polymeric composition is less than 1000 ppm. 
     
     
         6 . The implantable medical device of  claim 5 , wherein the implantable drug delivery device is deformable. 
     
     
         7 . The implantable medical device of  claim 6 , wherein the implantable drug delivery device is a stent. 
     
     
         8 . The implantable medical device of  claim 1 , wherein the drug-containing polymeric composition further comprises one or more radiopaque additives. 
     
     
         9 . An implantable medical device made by a method comprising:
 forming a drug-containing polymeric composition comprising a biocompatible polymeric matrix with one or more therapeutic agents, wherein said polymeric matrix further comprises one or more organic or aqueous solvents, the polymeric matrix comprising at least two polymers;   oven drying the drug-containing polymeric composition for first period of time so as to reduce solvent content in the polymeric matrix;   subsequently removing additional solvents from the drug-containing polymeric composition after oven drying the composition utilizing a supercritical carbon dioxide process to reduce solvent content in the polymeric matrix to an amount less than about 10,000 ppm of the polymeric matrix, wherein the first period of time is at least six hours to reduce porosity in the drug-containing polymeric composition during the supercritical carbon dioxide process; and   forming at least a portion of the implantable drug device with the drug-containing composition.   
     
     
         10 . The implantable medical device of  claim 9 , wherein the drug-containing polymeric composition comprises a polymeric blend containing a first, stiffer biocompatible polymer and a second, softer biocompatible polymer. 
     
     
         11 . The implantable medical device of  claim 9 , wherein the drug-containing polymeric composition comprises a polymer and a plasticizer. 
     
     
         12 . The implantable medical device of  claim 9 , wherein the super-critical drying process is carried out by using supercritical carbon dioxide at a temperature ranging from about 25° C. to about 50° C. and a pressure ranging from about 10 bars to about 500 bars. 
     
     
         13 . The implantable medical device of  claim 9 , wherein the solvent content in the drug-containing polymeric composition is less than 1000 ppm. 
     
     
         14 . The implantable medical device of  claim 13 , wherein the implantable drug delivery device is deformable. 
     
     
         15 . The implantable medical device of  claim 14 , wherein the implantable drug delivery device is a stent. 
     
     
         16 . The implantable medical device of  claim 1 , wherein the drug-containing polymeric composition further comprises one or more radiopaque additives. 
     
     
         17 . A drug-containing polymeric composition comprising a biocompatible polymeric matrix with one or more therapeutic agents encapsulated therein, wherein said polymeric matrix further comprises at least two polymers and one or more organic solvents in an amount less than 10,000 ppm. 
     
     
         18 . The drug-containing polymeric composition of  claim 18 , comprising one or more organic solvents in an amount less than 1000 ppm. 
     
     
         19 . The drug-containing polymeric composition of  claim 18 , comprising one or more organic solvents in an amount less than 100 ppm. 
     
     
         20 . The drug-containing polymeric composition of  claim 18 , comprising a polymeric blend containing a first, stiffer biocompatible polymer and a second, softer biocompatible polymer. 
     
     
         21 . The drug-containing polymeric composition of  claim 18 , comprises a polymer and a plasticizer. 
     
     
         22 . The drug-containing polymeric composition of  claim 17 , further comprising one or more radiopaque additives.