Drug delivery devices for delivery of ocular therapeutic agents

Abstract

Drug delivery devices comprising a non-bioabsorbable polymer structure configured to support a composition comprising an active agent. The devices include a plurality of portions fused together and a recess configured to support the composition. At least one of the portions includes an impermeable polymer and at least one other portion includes a rate-limiting water-permeable polymer. The rate-limiting water-permeable polymer allows for transportation of the active agent to an exterior of the device.

1 . A device for insertion in the eye, the device comprising:
 a first portion including a recess configured to support a composition comprising an active agent, the first portion comprising an impermeable polymer; and   a second portion fused to the first portion, the second portion comprising a rate-limiting water-permeable polymer that allows for transportation of the active agent to an exterior of the device, wherein the rate-limiting water-permeable polymer includes a thickness in a range of about 20 μm to about 500 μm.   
     
     
         2 . The device set forth in  claim 1  further comprising
 a flange fused to the second portion. 
 
     
     
         3 . The device set forth in  claim 1  wherein
 the second portion includes a base and a flange integral with the base. 
 
     
     
         4 . A device for insertion in the eye, the device comprising:
 a first portion comprising a rate-limiting water-permeable polymer;   a second portion fused to the first portion, the second portion including a recess configured to support a composition comprising an active agent, the second portion comprising a rate-limiting water-permeable polymer; and   a third portion fused to the second portion, the third portion comprising a rate-limiting water-permeable polymer,   wherein the rate-limiting water-permeable polymer includes a thickness in a range of about 20 μm to about 500 μm and allows for transportation of the active agent to an exterior of the device.   
     
     
         5 . A device for insertion in the eye, the device comprising:
 a non-bioabsorbable polymer structure comprising a rate-limiting water-permeable polymer; and   a composition supported within an enclosure of the non-bioabsorbable polymer structure, the composition including an active agent;   wherein the non-bioabsorbable polymer structure includes a thickness in a range of about 200 μm to about 800 μm, and wherein the thickness is configured to control an elution rate of the active agent through the rate-limiting water-permeable polymer, wherein the rate-limiting water-permeable polymer is a copolymer having both hydrophobic and hydrophilic monomers.   
     
     
         6 . The device set forth in  claim 5 , wherein the rate-limiting water-permeable polymer is selected from the group consisting of: ethylene vinyl acetate with a vinyl acetate content of about 10% to about 50% by weight (EVA-10-50) and ethylene vinyl alcohol with a vinyl alcohol content of about 40% to about 80% by weight (EVOH-40-80). 
     
     
         7 . (canceled) 
     
     
         8 . The device set forth in  claim 5 , wherein the active agent is selected from the group consisting of: 3-hydroxy-2,2-bis(hydroxymethyl)propyl 7-((1R,2R,3R,5S)-2-((R)-3-(benzo[b]thiophen-2-yl)-3-hydroxypropyl)-3,5-dihydroxycyclopentyl)heptanoate (AR-102), 7-((1R,2R,3R,5S)-2-((R)-3-(benzo[b]thiophen-2-yl)-3-hydroxypropyl)-3,5-dihydroxycyclopentyl)heptanoic acid (AR-102 free acid), dorzolamide, ethacrynic acid, latanoprost, latanoprost free acid, travoprost, travoprost free acid, bimatoprost, bimatoprost free acid, tafluprost, tafluprost free acid, dexamethasone, brimonidine, timolol, or salts thereof. 
     
     
         9 . A method of treating an ocular condition comprising inserting the device of any one of  claims 5 ,  6 , and  8  to the conjunctiva of the eye. 
     
     
         10 . The method of  claim 9  wherein the device is inserted into the upper or lower formix of the eye. 
     
     
         11 . A method of treating an ocular condition comprising implanting episclerally or supraconjunctivally a drug delivery device comprising an active agent, wherein the active agent is released at a rate of about 0.0001 to about 200 micrograms/hr. 
     
     
         12 . The method of  claim 11 , wherein the active agent is released at a rate of about 0.0001 to about 30 micrograms/hr. 
     
     
         13 . The method of  claim 11 , wherein the active agent is released at a rate of about 0.001 micrograms/hr to about 30 micrograms/hr. 
     
     
         14 . The method of  claim 11 , wherein the active agent is released at a rate of about 0.001 micrograms/hr to about 10 micrograms/hr. 
     
     
         15 . The method of  claim 11 , wherein the active agent comprises a prostaglandin active agent, the active agent being implanted episclerally and being released at a rate of about 0.00025 to about 0.0075 micrograms/hr. 
     
     
         16 . The method of  claim 15 , wherein the active agent comprises latanoprost, travoprost, bimatoprost, each of their free acids or salts. 
     
     
         17 . The method of  claim 11 , wherein the active agent comprises a prostaglandin active agent, the active agent being implanted supraconjunctivally and being released at a rate of about 0.0005 to about 0.015 micrograms/hr. 
     
     
         18 . The method of  claim 17 , wherein the active agent comprises latanoprost, travoprost, bimatoprost, each of their free acids or salts. 
     
     
         19 . The method of  claim 11 , wherein the active agent comprises a rho-kinase active agent, the active agent being implanted episclerally, and being released at a rate of about 0.02 to about 0.6 micrograms/hr. 
     
     
         20 . The method of  claim 19 , wherein the active agent comprises a Y-39983 salt. 
     
     
         21 . The method of  claim 11 , wherein the active agent comprises a rho-kinase active agent, the active agent being implanted supraconjunctivally and being released at a rate of about 0.04 to about 1.2 micrograms/hr. 
     
     
         22 . The method of  claim 21 , wherein the active agent comprises a Y-39983 salt. 
     
     
         23 . The method of  claim 11 , wherein the active agent is a non-prostaglandin and non-rho-kinase active agent, the active agent being implanted episclerally and being released at a rate of about 0.25 to about 7.5 micrograms/hr. 
     
     
         24 . The method of  claim 23 , wherein the active agent comprises timolol or a salt thereof. 
     
     
         25 . The method of  claim 11 , wherein the active agent is a non-prostaglandin and non-rho-kinase active agent, the active agent being implanted supraconjunctivally and being released at a rate of about 0.5 to about 15 micrograms/hr. 
     
     
         26 . The method of  claim 25 , wherein the active agent comprises timolol or a salt thereof. 
     
     
         27 . The device set forth in  claim 1 , wherein the device is substantially cylindrical-shaped. 
     
     
         28 . The device set forth in  claim 4 , wherein the device is substantially cylindrical-shaped. 
     
     
         29 . The device set forth in  claim 5 , wherein the device is substantially cylindrical-shaped.