Composition, system, and method for modulating release kinetics in implantable drug delivery devices by modifying drug solubility

Abstract

An implantable drug delivery device loaded with a beneficial agent is provided, wherein the beneficial agent is in two different forms, a first form having a higher solubility and a second form having a lower solubility, and wherein the two different forms are present in a proportion which is selected to achieve a desired release rate.

1 . An implantable drug delivery device comprising: 
 an implantable device configured to be implanted within tissue, lumens, or organs of the body;    a beneficial agent provided in or on the implantable medical device for delivery to the tissue, lumen, or organ of the body to achieve a desired beneficial effect;    wherein the beneficial agent is provided in two different forms, a first form having a higher solubility and a second form having a lower solubility, and wherein the two different forms are present in a proportion which is selected to achieve a desired release rate.    
     
     
         2 . The device of  claim 1 , wherein the implantable device is microspheres, microparticles, nanospheres, or nanoparticles.  
     
     
         3 . The device of  claim 1 , wherein the implantable device is a metallic implant.  
     
     
         4 . The device of  claim 1 , wherein the implantable device is a stent.  
     
     
         5 . The device of  claim 1 , wherein beneficial agent is coated on the implantable device.  
     
     
         6 . The device of  claim 1 , wherein the beneficial agent contained in reservoirs in the implantable medical device.  
     
     
         7 . The device of  claim 6 , wherein the different forms of the beneficial agent are contained in different reservoirs.  
     
     
         8 . The device of  claim 6 , wherein the different forms of the beneficial agent are contained in the same reservoir.  
     
     
         9 . The device of  claim 1 , wherein the first form is a salt form and the second form is a free base form of the agent.  
     
     
         10 . The device of  claim 1 , wherein the first form is a salt form and the second form is an acid form.  
     
     
         11 . The device of  claim 1 , wherein the first form and the second form are different ionic forms of the agent.  
     
     
         12 . The device of  claim 1 , wherein the first form includes an inclusion complex and the second form includes no inclusion complex or less inclusion complex than the first form.  
     
     
         13 . The device of  claim 1 , wherein the first form includes a solubilization agent and the second form includes no solubilization agent or less solubilization agent.  
     
     
         14 . The device of  claim 1 , wherein the first form is a different crystal form, hydrate, or solvate from the second form.  
     
     
         15 . The device of  claim 1 , wherein the beneficial agent is imatinib and the first and second forms are free-base and salt forms.  
     
     
         16 . A method of forming an implantable drug delivery device comprising: 
 selecting an implantable device configured to be implanted within tissue, lumens, or organs of the body;    providing a beneficial agent in two different forms, a first form having a higher solubility and a second form having a lower solubility;    selecting a proportion of the two different forms to achieve a desired release rate;    affixing the beneficial agent in the two different forms and in the selected proportion to the implantable device.    
     
     
         17 . The method of  claim 16 , wherein the two different forms of the beneficial agent are mixed together before affixing to the implantable device.  
     
     
         18 . The method of  claim 16 , wherein the two different forms of the beneficial agent are maintained separate when affixed to the implantable device.  
     
     
         19 . The method of  claim 16 , wherein the implantable device is microspheres, microparticles, nanospheres, or nanoparticles.  
     
     
         20 . The method of  claim 16 , wherein the implantable device is a metallic implant.  
     
     
         21 . The method of  claim 16 , wherein the implantable device is a stent.  
     
     
         22 . The method of  claim 16 , wherein beneficial agent is coated on the implantable device.  
     
     
         23 . The method of  claim 16 , wherein the beneficial agent is contained in reservoirs in the implantable medical device.  
     
     
         24 . The method of  claim 16 , wherein the first form is a salt form and the second form is a free base form of the agent.  
     
     
         25 . The method of  claim 16 , wherein the first form is a salt form and the second form is an acid form.  
     
     
         26 . The method of  claim 16 , wherein the first form and the second form are different ionic forms of the agent.  
     
     
         27 . The method of  claim 16 , wherein the first form includes an inclusion complex and the second form includes no inclusion complex or less inclusion complex than the first form.  
     
     
         28 . The method of  claim 16 , wherein the first form includes a solubilization agent and the second form includes no solubilization agent or less solubilization agent.  
     
     
         29 . The method of  claim 16 , wherein the first form is a different crystal form, hydrate, or solvate from the second form.  
     
     
         30 . The method of  claim 16 , wherein the beneficial agent is imatinib and the first and second forms are free-base and salt.