Morphology Profiles For Control Of Agent Release Rates From Polymer Matrices

Abstract

The present disclosure teaches methods of controlling the release rate of agents from a polymeric matrix that include designing and creating a predetermined initial morphology (IM) profile in a polymeric matrix. The teachings indicate, inter alia, that control over the release rate of agents can provide for an improved control over the administration of agents as well as have an effect upon the mechanical integrity and absorption rate of the polymeric matrix.

1 . A method for coating an implantable medical device comprising:
 (a) applying a polymer composition onto the device, the polymer composition comprising one or more polymers, one or more bioactive agents, and one or more solvents; and   (b) drying the polymer composition for a period of time at room temperature in an environment having relative humidity about 20% or lower than 20%;   wherein at least one of the one or more polymers is a polymer formed from one or more constituent monomers, the constituent monomer(s) comprising D-lactide, D,L-lactide, L-lactide, L-lactic acid, D-lactic acid, D,L-lactic acid, or a combination thereof.   
     
     
         2 . The method of  claim 1 , wherein at least one of the one or more bioactive agents is rapamycin, methyl rapamycin, zotarolimus, everolimus, tacrolimus, pimecrolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein at least one of the one or more solvents is DMAC, DMF, THF, cyclohexanone, xylene, toluene, acetone, i-propanol, methyl ethyl ketone, propylene glycol monomethyl ether, methyl butyl ketone, ethyl acetate, n-butyl acetate, dioxane, or a mixture thereof. 
     
     
         4 . The method of  claim 1 , wherein the medical device is a stent. 
     
     
         5 . The method of  claim 2 , wherein the medical device is a stent. 
     
     
         6 . The method of  claim 3 , wherein the medical device is a stent. 
     
     
         7 . The method of  claim 3 , wherein the thickness of the coating formed is in the range of 0.1 nm to 100 μm. 
     
     
         8 . The method of  claim 3 , wherein the thickness of the coating formed is in the range of 10 μm to 50 μm. 
     
     
         9 . The method of  claim 6 , wherein the thickness of the coating formed is in the range of 0.1 nm to 100 μm. 
     
     
         10 . The method of  claim 6 , wherein the thickness of the coating formed is in the range of 10 μm to 50 μm. 
     
     
         11 . The method of  claim 4 , wherein at least one of the one or more polymers is poly(lactide-co-glycolide), poly(D,L-lactic acid), poly(D,L-lactide), poly(glycolic acid-co-trimethylene carbonate), or a combination thereof. 
     
     
         12 . The method of  claim 5 , wherein at least one of the one or more polymers is poly(lactide-co-glycolide), poly(D,L-lactic acid), poly(D,L-lactide), poly(glycolic acid-co-trimethylene carbonate), or a combination thereof. 
     
     
         13 . The method of  claim 6 , wherein at least one of the one or more polymers is poly(lactide-co-glycolide), poly(D,L-lactic acid), poly(D,L-lactide), poly(glycolic acid-co-trimethylene carbonate), or a combination thereof. 
     
     
         14 . The method of  claim 2 , wherein at least one of the one or more bioactive agents is rapamycin, zotarolimus, everolimus, tacrolimus, pimecrolimus, or a combination thereof. 
     
     
         15 . The method of  claim 5 , wherein at least one of the one or more bioactive agents is rapamycin, zotarolimus, everolimus, tacrolimus, pimecrolimus, or a combination thereof. 
     
     
         16 . The method of  claim 6 , wherein at least one of the one or more bioactive agents is rapamycin, zotarolimus, everolimus, tacrolimus, pimecrolimus, or a combination thereof. 
     
     
         17 . The method of  claim 3 , wherein at least one of the one or more solvents is acetone, i-propanol, methyl ethyl ketone, propylene glycol monomethyl ether, methyl butyl ketone, or a mixture thereof. 
     
     
         18 . The method of  claim 6 , wherein at least one of the one or more solvents is acetone, i-propanol, methyl ethyl ketone, propylene glycol monomethyl ether, methyl butyl ketone, or a mixture thereof. 
     
     
         19 . The method of  claim 10 , wherein at least one of the one or more solvents is acetone, i-propanol, methyl ethyl ketone, propylene glycol monomethyl ether, methyl butyl ketone, or a mixture thereof. 
     
     
         20 . The method of  claim 19 , wherein the one or more solvents comprise acetone, and the at least one of the one or more bioactive agents is rapamycin, zotarolimus, everolimus, tacrolimus, pimecrolimus, or a combination thereof, and the one or more polymers is poly(D,L-lactide) or a combination of poly(D,L-lactide) and one or more other polymers.