DELIVERY OF CORTICOSTEROIDS THROUGH IONTOPHORESIS
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.