Medical Device with Crystalline Drug Coating

Abstract

A medical device having a polymer-free outer surface layer comprising a crystalline drug selected from the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin. The device may be produced by a method comprising the steps of providing a medical device; applying a solution of the drug to said portion of the outer surface to form a coating of amorphous drug; and vapor annealing the drug with a solvent vapor to form crystalline drug; wherein a seed layer of a crystalline form of said drug having a maximum particle size of about 10 μm or less is applied to at least said portion of the outer surface of the device before or after applying the drug solution, but before vapor annealing the amorphous coating.

1 . A medical device having a polymer-free outer surface layer on at least a portion thereof, said layer comprising a crystalline drug selected from the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin. 
     
     
         2 . A medical device as in  claim 1  wherein the drug is everolimus. 
     
     
         3 . A medical device as in  claim 2  wherein the crystalline form everolimus comprises at least 85% by weight of the drug. 
     
     
         4 . A medical device as in  claim 10  wherein the crystalline form everolimus comprises at least 90% by weight of the drug. 
     
     
         5 . A medical device as in  claim 2  wherein the polymer-free coating comprises a mixture of crystalline and amorphous everolimus, the mixture comprising from 15% to 90% by weight of said crystalline everolimus. 
     
     
         6 . A medical device as in  claim 1  wherein the crystalline layer is formed-in-place with a crystalline morphology having a generally rectilinear form characterized by a major dimension of length and minor dimensions of width and thickness. 
     
     
         7 . A medical device as in  claim 6  wherein said crystalline morphology is formed by individual crystals having with an average length of less than 50 μm, an average width of less than 10 μm and an average thickness of less than 1.5 μm. 
     
     
         8 . A medical device as in  claim 1  wherein said outer surface layer further comprises a non-polymeric excipient. 
     
     
         9 . A medical device as in  claim 8  wherein said non-polymeric excipient is a wax, fat, oil or a citrate ester. 
     
     
         10 . A medical device as in  claim 1  wherein said outer surface layer is free of any excipient. 
     
     
         11 . A medical device as in  claim 1  wherein the medical device is a stent, a catheter balloon, guide wire, heart valve, catheter, vena cava filter, vascular graft or a stent graft. 
     
     
         12 . A medical device as in as in  claim 1  wherein the device is a metal stent, the outer layer is free of any excipient, and the coating is provided in grooves or depressions on the outer surface of the stent.