Topical drug delivery systems for ophthalmic use
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.
1. An aqueous ophthalmic solution comprising nanomicelles in a physiologically acceptable buffer, having a pH of 5.0 to 8.0, wherein the nanomicelles consist essentially of dexamethasone, vitamin E TPGS and octoxynol-40, wherein the dexamethasone 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 vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v is stabilized with the octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v, wherein the aqueous ophthalmic solution is stable after about 40 days at about 4° C.
2. The aqueous ophthalmic solution of claim 1 wherein the concentration of the dexamethasone is from about 0.05% w/v to about 0.25% w/v.
3. The aqueous ophthalmic solution of claim 1 wherein the pH is in a range from about 6.6 to about 7.0.
4. 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.
5. 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.
6. An eye drop formulation comprising nanomicelles in a physiologically acceptable buffer, wherein the nanomicelles consist essentially of:
dexamethasone 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 dexamethasone is solubilized through entrapment in a mixed micellar hydrophobic core of the vitamin E TPGS and the octoxynol-40, wherein the aqueous ophthalmic solution is stable after about 40 days at about 4° C.
7. The eye drop formulation of claim 6 wherein the concentration of the dexamethasone is from about 0.05% w/v to about 0.25% w/v.
8. The eye drop formulation of claim 6 wherein the concentration of the vitamin E TPGS is from about 4.0% w/v to about 5.0% w/v.
9. The eye drop formulation of claim 6 wherein the concentration of the octoxynol-40 is from about 1.5% w/v to about 2.5% w/v.
10. The eye drop formulation of claim 6 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.
11. 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 the nanomicelles consist essentially of dexamethasone, vitamin E TPGS and octoxynol-40, wherein the dexamethasone 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 vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v is stabilized with the 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, wherein the aqueous ophthalmic solution is stable after about 40 days at about 4° C.
12. The kit of claim 11 wherein the unit dose is about 50 μL.
13. The kit 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.
14. The kit of claim 11 wherein the pharmaceutically acceptable packaging material is low density polyethylene or high density polyethylene.
15. A method of treating a back-of-the-eye ocular condition with dexamethasone in a patient in need thereof 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 the nanomicelles consist essentially of dexamethasone, vitamin E TPGS and octoxynol-40, wherein the dexamethasone 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 vitamin E TPGS at a concentration ranging from about 2.0% w/v to about 5.0% w/v is stabilized with the octoxynol-40 at a concentration ranging from about 1.0% w/v to about 3.0% w/v, wherein the aqueous ophthalmic solution is stable after about 40 days at about 4° C.
16. The method of claim 15 wherein the dexamethasone is 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.