Ocular implant made by a double extrusion process

Abstract

The invention provides biodegradable implants sized for implantation in an ocular region and methods for treating medical conditions of the eye. The implants are formed from a mixture of hydrophilic end and hydrophobic end PLGA, and deliver active agents into an ocular region without a high burst release.

1 . A bioerodible implant for treating an ocular condition comprising an active agent dispersed within a biodegradable polymer matrix, wherein at least about 75% of the particles of the active agent have a diameter of less than about 10 μm.  
     
     
         2 . The implant of  claim 1 , wherein at least about 99% of the particles of the active agent have a diameter of less than about 20 μm.  
     
     
         3 . The bioerodible implant of  claim 1  wherein the active agent is selected from the group consisting of ace-inhibitors, endogenous cytokines, agents that influence basement membrane, agents that influence the growth of endothelial cells, adrenergic agonists or blockers, cholinergic agonists or blockers, aldose reductase inhibitors, analgesics, anesthetics, antiallergics, anti-inflammatory agents, steroids, antihypertensives, pressors, antibacterials, antivirals, antifungals, antiprotozoals, anti-infective agents, antitumor agents, antimetabolites, and antiangiogenic agents.  
     
     
         4 . The bioerodible implant of  claim 1  wherein the active agent comprises an anti-inflammatory agent or any derivative thereof.  
     
     
         5 . The bioerodible implant of  claim 1  wherein the active agent comprises a steroidal anti-inflammatory agent or any derivative thereof.  
     
     
         6 . The bioerodible implant of  claim 4  wherein the active agent is selected from the group consisting of cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, and any derivative thereof.  
     
     
         7 . The bioerodible implant of  claim 1  wherein the active agent comprises dexamethasone.  
     
     
         8 . The bioerodible implant of  claim 1  wherein the implant is sized for implantation in an ocular region.  
     
     
         9 . The bioerodible implant of  claim 8  wherein the ocular region is selected from the group consisting of the anterior chamber, the posterior chamber, the vitreous cavity, the choroid, the suprachoroidal space, the conjunctiva, the subconjunctival space, the episcleral space, the intracorneal space, the epicorneal space, the sclera, the pars plana, surgically-induced avascular regions, the macula, and the retina.  
     
     
         10 . The bioerodible implant of  claim 9  wherein the ocular region is the vitreous cavity.  
     
     
         11 . A bioerodible implant for treating an ocular condition comprising a steroid active agent dispersed within a biodegradable polymer matrix, wherein at least about 75% of the particles of the steroid active agent have a diameter of less than about 20 μm.  
     
     
         12 . The bioerodible implant of  claim 11  wherein the steroid active agent is selected from the group consisting of cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, and any derivative thereof.  
     
     
         13 . The bioerodible implant of  claim 12  wherein the steroid active agent comprises dexamethasone.  
     
     
         14 . A method for making a bioerodible implant for treating an ocular condition of the eye, the method comprising a plurality of extrusions of a biodegradable polymer.  
     
     
         15 . The method of  claim 14  further comprising the step of milling the biodegradable polymer prior to the extrusion.  
     
     
         16 . The method of  claim 14 , wherein the biodegradable polymer comprises poly(lactic-co-glycolic)acid (PLGA) copolymer.  
     
     
         17 . The method of  claim 16  wherein the ratio of lactic to glycolic acid monomers is about 50/50 weight percentage.  
     
     
         18 . The bioerodible implant of  claim 16  wherein the PLGA copolymer is about 20 to about 90 weight percent of the bioerodible implant.  
     
     
         19 . The method of  claim 18  wherein the PLGA copolymer is about 40 percent by weight of the bioerodible implant.  
     
     
         20 . A method for making a bioerodible implant for treating an ocular condition, the method comprising the steps of: 
 (a) milling a biodegradable polymer;    (b) blending the milled biodegradable polymer and particles of an active agent, to thereby obtain a blended mixture of the milled biodegradable polymer and the particles of the active agent, wherein at least about 75% of the particles of the active agent have a diameter of less than about 20 μm;    (c) carrying out a first extrusion of the blended mixture, to thereby obtain a first extrusion product;    (d) pelletizing the first extrusion product, and;    (e) carrying out a second extrusion of the pelletized first extrusion product, thereby obtaining a bioerodible implant for an ocular condition.    
     
     
         21 . A bioerodible implant for treating an ocular condition made by the method of  claim 14.