Drug cores for sustained release of therapeutic agents

Abstract

A solid drug core insert can be manufactured by injecting a liquid mixture comprising a therapeutic agent and a matrix precursor into a sheath body. The injection can be conducted at subambient temperatures. The mixture is cured to form a solid drug-matrix core. The therapeutic agent can be a liquid at about room temperature that forms a dispersion of droplets in the matrix material. A surface of the solid drug core is exposed, for example by cutting the tube, and the exposed surface of the solid drug core releases therapeutic quantities of the therapeutic agent when implanted into the patient. In some embodiments, the insert body inhibits release of the therapeutic agent, for example with a material substantially impermeable to the therapeutic agent, such that the therapeutic quantities are released through the exposed surface, thereby avoiding release of the therapeutic agent to non-target tissues.

What is claimed is: 
     
         1 . A drug insert for an implant body adapted for disposition within or adjacent to a body cavity, tissue, duct or fluid of a patient, wherein the drug insert comprises:
 a cured mixture comprising latanoprost and a silicone matrix, wherein the latanoprost is dispersed within the mixture as inclusions with an average diameter of less than about 10 μm; and   an impermeable sheath body partially covering the cured mixture to provide at least one exposed surface.   
     
     
         2 . The drug insert of  claim 1 , wherein the implant is adapted for disposition in or adjacent to an eye of a patient. 
     
     
         3 . The drug insert of  claim 1 , wherein the implant body comprises a punctal plug adapted to be disposed within the punctum of the patient. 
     
     
         4 . The drug insert of  claim 1 , wherein the inclusions of latanoprost are uniformly and homogeneously dispersed throughout the cured mixture. 
     
     
         5 . The drug insert of  claim 1 , wherein the amount of the latanoprost in a volumetric portion of the cured mixture varies from the amount of the latanoprost in any other equal volumetric portion of the cured mixture by no greater than about 10%. 
     
     
         6 . The drug insert of  claim 1 , wherein the amount of the latanoprost in a volumetric portion of the cured mixture varies from the amount of the latanoprost in any other equal volumetric portion of the cured mixture by no greater than about 5%. 
     
     
         7 . The drug insert of  claim 1 , further comprising a seal on one end of the drug insert wherein a second end is the exposed surface. 
     
     
         8 . The drug insert of  claim 1 , wherein the one end is sealed with a UV-curable adhesive, a cyanoacrylate, an epoxy, by pinching, with a heat weld, or with a cap. 
     
     
         9 . The drug insert of  claim 1 , wherein the insert comprises about 0.1 wt % to about 50 wt % of the latanoprost. 
     
     
         10 . The drug insert of  claim 1 , wherein the insert comprises about 10 wt % to about 50 wt % of the latanoprost. 
     
     
         11 . The drug insert of  claim 1 , wherein the insert comprises about 20 wt % to about 50 wt % of the latanoprost. 
     
     
         12 . The drug insert of  claim 1 , wherein the sheath body comprises at least one of polyimide, PMMA, PET, stainless steel, or titanium. 
     
     
         13 . The drug insert of  claim 1 , wherein the drug insert is about 0.80 to about 1.0 mm in length. 
     
     
         14 . The drug insert of  claim 1 , wherein the drug insert has a diameter of about 0.2 to about 0.75 mm. 
     
     
         15 . The drug insert of  claim 1 , wherein the average diameter of the latanoprost inclusions are uniform in size and shape throughout the cured mixture. 
     
     
         16 . The drug insert of  claim 1 , wherein the drug insert is configured to elute at least about 100 ng per day of the latanoprost. 
     
     
         17 . The drug insert of  claim 1 , wherein the drug insert is configured to elute a therapeutic level of the latanoprost during a treatment period of at least 20 days. 
     
     
         18 . The drug insert of  claim 1 , wherein the cured mixture further comprises a salt. 
     
     
         19 . The drug insert of  claim 1 , wherein the inclusions of latanoprost have an average diameter of less than about 7 μm.