Topical Drug Delivery Systems for Ophthalmic Use

• US 20100310642A1
• Filed: 05/05/2010
• Published: 12/09/2010
• Est. Priority Date: 06/09/2009
• Status: Active Grant

• Current Assignee: Aurinia Pharmaceuticals Inc.
• Original Assignee: Lux Biosciences, Inc.
• Inventors: Velagaleti, Poonam R., Grau, Ulrich M., Mitra, Ashim K.
• Granted Patent: US 9,017,725 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/14 Quaternary ammonium compounds, e.g. edrophonium, choline betaines A61K31/205
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents

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.

Claims

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 μ

L.

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.