Delivery of corticosteroids through iontophoresis

Abstract

Disclosed herein are formulations of dexamethasone or a prodrug thereof suitable for delivery by ocular iontophoresis and methods of use thereof.

1 . A method for iontophoretically delivering a corticosteroid, corticosteroid derivative, prodrug or salt thereof into the eye of a subject, comprising:
 a) administering the compound to the eye of the subject; and   b) performing ocular iontophoresis under conditions such that the pH is between about 2.5 and about 6.5,   thereby delivering the compound into the eye.   
   
   
       2 . The method of  claim 1 , wherein the corticosteroid is a dexamethasone compound, derivative thereof. 
   
   
       3 . The method of  claim 2 , wherein the starting pH is about 5.7. 
   
   
       4 . The method of  claim 1 , wherein the corticosteroid is in the form of a prodrug. 
   
   
       5 . The method of  claim 1 , wherein the corticosteroid is delivered by injection prior to iontophoresis. 
   
   
       6 . The method of  claim 5 , wherein the method of injection is selected from the group consisting of: an intracameral injection, an intracorneal injection, a subconjonctival injection, a subtenon injection, a subretinal injection, an intravitreal injection and an injection into the anterior chamber. 
   
   
       7 . The method of  claim 1 , wherein the corticosteroid is administered topically prior to iontophoresis. 
   
   
       8 . The method of  claim 7 , wherein the topical administration comprises providing the corticosteroid in a form selected from the group consisting of: a liquid solution, a paste and a hydro gel. 
   
   
       9 . The method of  claim 7 , wherein the corticosteroid is embedded in a foam matrix. 
   
   
       10 . The method of  claim 7 , wherein the corticosteroid is supported in a reservoir. 
   
   
       11 . The method of  claim 1 , wherein the step of ocular iontophoresis is carried out prior to, during or after the step of administering the corticosteroid. 
   
   
       12 . The method of  claim 1 , wherein the compound is delivered by an iontophoretic dose of about 1.7×10 −4  mA·min to about 120 mA·min. 
   
   
       13 . The method of  claim 12 , wherein the compound is delivered by an iontophoretic dose of between about 10 mA·min and about 30 mA·min. 
   
   
       14 . The method of  claim 13 , wherein the iontophoretic dose is about 20 mA·min. 
   
   
       15 . The method of  claim 14 , wherein the compound is delivered at a current of about 4.0 mA for a period of about 5 minutes. 
   
   
       16 . The method of  claim 12 , wherein the compound is delivered at a variable or fixed current of less than about 10 mA. 
   
   
       17 . The method of  claim 12 , wherein the compound is delivered for a time of less than about 10 minutes. 
   
   
       18 . A kit for iontophoretically delivering dexamethasone into the eye of a subject, wherein the kit is to be used for iontophoresis between a pH range of about 2.5 to about 6.5, and an apparatus for iontophoretically delivering the compound into the eye of a subject. 
   
   
       19 . A dexamethasone formulation suitable for ocular iontophoretic delivery into the eye of a subject. 
   
   
       20 . The formulation of  claim 19 , wherein the dexamethasone is in the form of a prodrug. 
   
   
       21 . The formulation of  claim 19 , wherein iontophoretic delivery is to be performed in a pH range of between about 2.5 and about 6.5. 
   
   
       22 . The formulation of  claim 21 , wherein the pH is about 5.7. 
   
   
       23 . A device for delivering dexamethasone, comprising:
 a) a reservoir comprising at least at least one medium comprising a dexamethasone formulation, the reservoir extending along a surface intended to cover a portion of an eyeball; and   b) an electrode associated with the reservoir so as to, when polarized, supply an electric field directed through the medium and toward a surface of the eye,   wherein at least a portion of the dexamethasone formulation is delivered transdermally through the surface of the eye through iontophoresis.   
   
   
       24 . The device of  claim 23 , wherein the reservoir comprises;
 a) a first container for receiving the at least one medium comprising the dexamethasone formulation;   b) a second container for receiving an electrical conductive medium comprising electrical conductive elements; and   c) a semi-permeable membrane positioned between the first and second containers, the semi-permeable membrane being permeable to electrical conductive elements and non-permeable to the active substances.   
   
   
       25 . A method for treating a corticosteroid-sensitive ophthalmic disease in a mammal, comprising administering an effective amount of a corticosteroid by ocular iontophoresis. 
   
   
       26 . The method of  claim 25 , wherein the ophthalmic disease is selected from the group consisting of: uveitis, dry eye, post-operative inflammation and corneal graft rejection. 
   
   
       27 . The method of  claim 26 , wherein the corticosteroid is dexamethasone phosphate. 
   
   
       28 . The method of  claim 27 , wherein administration of dexamethasone phosphate occurs in a single dose.