System and method for ocular iontophoresis with buffering

• US 9,180,292 B2
• Filed: 12/28/2009
• Issued: 11/10/2015
• Est. Priority Date: 12/31/2008
• Status: Expired due to Fees

• Current Assignee: Eyegate Pharmaceuticals, Inc.
• Original Assignee: Eyegate Pharmaceuticals, Inc.
• Inventors: Moslemy, Peyman, Manzo, Michael, Schubert, William, Isom, William, Roy, Pierre
• Primary Examiner(s): Stigell, Theodore
• Assistant Examiner(s): PENG, LAUREN MICHELE
• Application Number:
  US13/141,810
• Publication Number:
  US 20110301526A1
• Time in Patent Office: 2,143 Days
• Field of Search: 604/20, 604/294, 604/521
• US Class Current: 1/1
• CPC Class Codes: A61F 9/0026 Ophthalmic product dispenser attachments to facilitate positioning near the eye
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir
• CPC Class Codes: A61N 1/303 Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

Compositions, devices, methods of manufacture, and methods of delivery of a therapeutic substance across a surface of an eyeball via iontophoresis including a therapeutic media reservoir and a buffer system within an iontophoretic chamber. When energized, an electrode provides an electromotive force that transfers a dosage of the therapeutic substance from the iontophoretic chamber across the surface of the eyeball. The buffering system includes a buffer media and at least one buffer element, or agent that regulates pH during iontophoretic transfer of the therapeutic substance. The buffer media includes at least one of a foam, a gel (solid or liquid), a membrane, and a plurality of multiparticulates. The buffer media can be included within the iontophoretic chamber, together with the therapeutic media reservoir, in various arrangements including one or more layers and one or more concentric cylinders.

Claims

1. A delivery device for transferring a therapeutic substance across and/or through a surface of an ocular globe, comprising:

an iontophoretic chamber configured to store the therapeutic substance;

an electrode disposed relative to the iontophoretic chamber, the electrode configured to provide an electromotive force, when energized, to transfer of at least a portion of the therapeutic substance stored within the iontophoretic chamber across and/or through the surface of the ocular globe;

a buffer system disposed at least partially within the at least one iontophoretic chamber, the buffer system does not contain the therapeutic substance, the buffer system configured to maintain a pH at the surface of the ocular globe within a range of about 3 to 8 during iontophoretic transfer of the therapeutic substance; and

the iontophoretic chamber further comprises a first layer and a removable second layer, the first layer including the buffer system and the second layer including a therapeutic substance, wherein the first layer is disposed closest to the electrode and wherein the second layer including the therapeutic substance is configured to be removably coupled to the iontophoretic chamber.

2. The delivery device of claim 1, wherein the buffer system includes a buffering agent to reduce the risk of damage to ocular tissue.

3. The delivery device of claim 2, wherein the buffer agent comprises at least one of an ion exchange resin, polymeric particles, insoluble buffer particles, cationic particles, anionic particles and zwitterionic particles.

4. The delivery device of claim 3, wherein the ion exchange resin comprises at least one ion exchange material having a characteristic nature of at least one of a strong acid, a strong base, a weak acid, and a weak base.

5. The delivery device of claim 2, wherein the buffer system further comprises a therapeutic substance.

6. The delivery device of claim 1, wherein the pH is maintained at a level substantially equal to the highest ionization level of the therapeutic substance to enhance transport efficiency of the therapeutic substance.

7. The delivery device of claim 1, wherein the buffer system is electrically conductive capable of conducting an electric field supplied from the electrode.

8. The delivery device of claim 1, wherein buffer system includes at least one of a porous material, a liquid solution, a gel, a packed bed resin, a hydro gel film, and a membrane.

9. The delivery device of claim 8, wherein the porous material comprises at least one of a foam, a fabric, a nonwoven material, and a sintered material.

10. The delivery device of claim 8, wherein of the gel comprises at least one of a hydrogel matrix and an aerogel matrix.

11. The delivery device of claim 8, wherein the membrane comprises at least one of a mono-laminar, a multi-laminar film, hydrophobic (semi permeable) membrane, and a non-permeable/solid membrane.

12. The delivery device of claim 1, further comprising a membrane disposed between the first layer and the second layer.

13. The delivery device of claim 12, wherein the membrane has low water vapor permeability to maintain water content in each layer.

14. The delivery device of claim 1, wherein the layers are arranged concentrically relative to each other.

15. The delivery device of claim 14, further comprising a membrane disposed between the first layer and the second layer.

16. The delivery device of claim 1, wherein first layer has a higher buffering capability than the second layer.

17. The delivery device of claim 1, wherein the buffer system is arranged as a buffered surface coating.

18. The delivery device of claim 1, wherein the buffer system further comprises a rehydrating agent.

19. The delivery device of claim 1, wherein the buffer system is disposed adjacent to the electrode.

20. The delivery device of claim 1, wherein a third layer is disposed between the first layer and the second layer, the third layer further including the buffer system.

21. The delivery device of claim 20, further comprising a membrane disposed between the first layer and the third layer or the second layer and the third layer.

22. The delivery device of claim 21, wherein the membrane has low water vapor permeability to maintain water content in each layer.

23. The delivery device of claim 20, wherein the layers are arranged concentrically relative to each other.

24. The delivery device of claim 23, further comprising a membrane disposed between the first layer and the third layer or the second layer and the third layer.

25. The delivery device of claim 20, wherein the first layer has a higher buffering capability than the third layer.

26. The delivery device of claim 20, wherein the third layer comprises a ionic composition that optimizes electro-transport of the therapeutic substance in the second layer.