Topical Drug Delivery System for Ophthalmic Use

Abstract

Topical drug delivery systems for ophthalmic use including mixed nanomicellar formulations of water-insoluble drugs and methods of treating diseases affecting the posterior ocular segments are disclosed. In an embodiment, an aqueous ophthalmic solution includes nanomicelles in a physiologically acceptable buffer, having a pH of 5.0 to 8.0, wherein a corticosteroid at a concentration from about 0.01% w/v to about 1.00% w/v is solubilized through entrapment in a mixed micellar hydrophobic core with a corona composed of hydrophilic chains extending from the hydrophobic core, wherein the nanomicelles comprise vitamin E TPGS at a concentration ranging from about 3.0% w/v to about 5.0% w/v stabilized with octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v.

What is claimed is: 
     
         1 . An aqueous ophthalmic solution comprising nanomicelles in a physiologically acceptable buffer, having a pH of 5.0 to 8.0, wherein a corticosteroid at a concentration ranging from about 0.01% w/v to about 1.00% w/v is solubilized through entrapment in a mixed micellar hydrophobic core with a corona composed of hydrophilic chains extending from the hydrophobic core, wherein the nanomicelles comprise vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v stabilized with octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v. 
     
     
         2 . The aqueous ophthalmic solution of  claim 1  wherein the concentration of the corticosteroid is from about 0.05% w/v to about 0.25% w/v. 
     
     
         3 . The aqueous ophthalmic solution of  claim 1  wherein the corticosteroid is selected from the group consisting of prednisolone, methylprednisolone, prednisone, triamcinolone, betamethasone, budesonide, and dexamethasone. 
     
     
         4 . The aqueous ophthalmic solution of  claim 1  wherein the corticosteroid is dexamethasone. 
     
     
         5 . The aqueous ophthalmic solution of  claim 1  wherein the pH is in a range from about 6.6 to about 7.0. 
     
     
         6 . The aqueous ophthalmic solution of  claim 1  wherein the concentration of the vitamin E TPGS is from about 4.0% w/v to about 5.0% w/v. 
     
     
         7 . The aqueous ophthalmic solution of  claim 1  wherein the concentration of the octoxynol-40 is from about 1.5% w/v to about 2.5% w/v. 
     
     
         8 . An eye drop formulation comprising:
 a corticosteroid at a concentration ranging from about 0.01% w/v to about 1.00% w/v;   vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v; and   octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v, wherein the corticosteroid is solubilized through entrapment in a mixed micellar hydrophobic core of the vitamin E TPGS and the octoxynol-40.   
     
     
         9 . The eye drop formulation of  claim 8  wherein the concentration of the corticosteroid is from about 0.05% w/v to about 0.25% w/v. 
     
     
         10 . The eye drop formulation of  claim 8  wherein the corticosteroid is selected from the group consisting of prednisolone, methylprednisolone, prednisone, triamcinolone, betamethasone, budesonide, and dexamethasone. 
     
     
         11 . The eye drop formulation of  claim 8  wherein the corticosteroid is dexamethasone. 
     
     
         12 . The eye drop formulation of  claim 8  wherein the concentration of the vitamin E TPGS is from about 4.0% w/v to about 5.0% w/v. 
     
     
         13 . The eye drop formulation of  claim 8  wherein the concentration of the octoxynol-40 is from about 1.5% w/v to about 2.5% w/v. 
     
     
         14 . The eye drop formulation of  claim 11  wherein the dexamethasone is present in the formulation at a concentration of about 0.1 wt % w/v, the vitamin E TPGS is present in the formulation at a concentration of about 4.5% w/v, and the octoxynol-40 is present in the formulation at a concentration of about 2.0% w/v. 
     
     
         15 . A kit comprising:
 a unit dose of an aqueous ophthalmic solution comprising nanomicelles in a physiologically acceptable buffer, having a pH of 5.0 to 8.0, wherein a corticosteroid at a concentration ranging from about 0.01% w/v to about 1.00% w/v is solubilized through entrapment in a mixed micellar hydrophobic core with a corona composed of hydrophilic chains extending from the hydrophobic core, wherein the nanomicelles comprise vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v stabilized with octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v, wherein the unit dose in contained within a vial prepared from a pharmaceutically acceptable packaging material.   
     
     
         16 . The kit of  claim 15  wherein the unit dose is about 50 μL. 
     
     
         17 . The kit of  claim 15  wherein the corticosteroid is dexamethasone, wherein the dexamethasone is present in the formulation at a concentration of about 0.1 wt % w/v, the vitamin E TPGS is present in the formulation at a concentration of about 4.5% w/v, and the octoxynol-40 is present in the formulation at a concentration of about 2.0% w/v. 
     
     
         18 . The kit of  claim 15  wherein the pharmaceutically acceptable packaging material is low density polyethylene or high density polyethylene. 
     
     
         19 . A method of treating a back-of-the-eye ocular condition comprising:
 administering to an eye of a patient an effective amount of an aqueous ophthalmic solution comprising nanomicelles in a physiologically acceptable buffer, having a pH of 5.0 to 8.0, wherein a corticosteroid at a concentration ranging from about 0.01% w/v to about 1.00% w/v is solubilized through entrapment in a mixed micellar hydrophobic core with a corona composed of hydrophilic chains extending from the hydrophobic core, wherein the nanomicelles comprise vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v stabilized with octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v.   
     
     
         20 . The method of  claim 19  wherein the corticosteroid is dexamethasone present in the solution at a concentration of about 0.1 wt % w/v, the vitamin E TPGS is present in the solution at a concentration of about 4.5% w/v, and the octoxynol-40 is present in the solution at a concentration of about 2.0% w/v.