Coatings with crystallized active agent(s) and methods

Abstract

The present invention relates to coatings with crystallized active agent(s) and related methods. In an embodiment, the invention includes a method for coating a medical device including selecting a solvent and a polymer, selecting a concentration of an active agent of at least a certain amount of saturation, forming a coating composition having the selected concentration of the active agent, and applying the coating composition to the medical device. In an embodiment, the invention includes an elution control coating disposed on a medical device, the elution control coating including a polymer, and an active agent, wherein the active agent is at least about 80% crystallized within one week of being disposed on the medical device. In an embodiment, the invention includes a method for enhancing the formation of active agent crystals within a coating layer including forming a coating solution and adjusting the concentration of the active agent in the coating solution to reach some percentage of the active agent saturation point. In an embodiment, the invention includes a method of enhancing crystallization of an active agent, the method including forming a coating solution comprising a polymer, an active agent, and a solvent; applying the coating solution to a substrate; and increasing the rate of active agent nucleation within the coating.

1 . A method for coating a medical device comprising: 
 selecting a solvent and a polymer;    selecting a concentration of an active agent at least 80% of saturation in a composition comprising the solvent and about 1.0 to about 99.0 wt. % polymer;    combining the active agent, the polymer, and the solvent to form a coating composition having the selected concentration of the active agent; and    applying the coating composition to the medical device.    
     
     
         2 . The method of  claim 1 , comprising selecting a concentration of an active agent at least 90% of saturation in a composition comprising the solvent and about 1.0 to about 99.0 wt. % polymer.  
     
     
         3 . The method of  claim 1 , comprising selecting a concentration of an active agent at least 95% of saturation in a composition comprising the solvent and about 1.0 to about 99.0 wt. % polymer.  
     
     
         4 . The method of  claim 1 , comprising selecting a concentration of an active agent at least 99% of saturation in a composition comprising the solvent and about 1.0 to about 99.0 wt. % polymer.  
     
     
         5 . The method of  claim 1 , the active agent comprising a steroid.  
     
     
         6 . The method of  claim 1 , the active agent comprising estradiol.  
     
     
         7 . The method of  claim 1 , the active agent comprising dexamethasone.  
     
     
         8 . The method of  claim 1 , the solvent comprising a first solvent and a second solvent; wherein the active agent is soluble in the first solvent and insoluble in the second solvent.  
     
     
         9 . The method of  claim 8 , the first solvent having a higher vapor pressure than the second solvent.  
     
     
         10 . The method of  claim 1 , the first solvent comprising THF and the second solvent comprising toluene.  
     
     
         11 . The method of  claim 1 , the polymer comprises a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the second polymer component is selected from the group consisting of poly(ethylene-co-vinyl acetate) polymers having vinyl acetate concentrations of between about 10% and about 50% by weight.  
     
     
         12 . The method of  claim 1 , the polymer comprises a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising polybutadiene.  
     
     
         13 . The method of  claim 1 , wherein the steps of combining and adjusting are performed simultaneously.  
     
     
         14 . An elution control coating disposed on a medical device, the elution control coating comprising: 
 a polymer, and    an active agent, wherein the active agent is at least about 80% crystallized within one week of being disposed on the medical device.    
     
     
         15 . The elution control coating of  claim 14 , wherein the active agent is at least about 90% crystallized within one week of being disposed on the medical device.  
     
     
         16 . The elution control coating of  claim 14 , wherein the active agent is at least about 95% crystallized within one week of being disposed on the medical device.  
     
     
         17 . The elution control coating of  claim 14 , wherein the active agent is at least about 95% crystallized within one day of being disposed on the medical device.  
     
     
         18 . The elution control coating of  claim 14 , the active agent comprising a steroid.  
     
     
         19 . The elution control coating of  claim 14 , the active agent comprising estradiol.  
     
     
         20 . The elution control coating of  claim 14 , the active agent comprising dexamethasone.  
     
     
         21 . The elution control coating of  claim 14 , the polymer comprises a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the second polymer component is selected from the group consisting of poly(ethylene-co-vinyl acetate) polymers having vinyl acetate concentrations of between about 10% and about 50% by weight.  
     
     
         22 . The elution control coating of  claim 14 , the polymer comprises a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising polybutadiene.  
     
     
         23 . A method for enhancing the formation of active agent crystals within a coating layer comprising: 
 combining a polymer, an active agent, and a solvent to form a coating solution comprising between 5 mg/ml and 200 mg/ml total solids concentration;    adjusting the concentration of the active agent in the coating solution to reach at least 80% of the active agent saturation point;    applying the coating solution to a device; and    evaporating the solvent to form crystals of the active agent.    
     
     
         24 . A method for enhancing crystallization of an active agent within an elution control coating, the method comprising: 
 forming a coating solution comprising a polymer, an active agent, and a solvent;    applying the coating solution to a substrate; and    increasing the rate of active agent nucleation within the coating.