Injectable sustained release delivery devices

• US 8,871,241 B2
• Filed: 11/13/2003
• Issued: 10/28/2014
• Est. Priority Date: 05/07/2002
• Status: Active Grant

• Current Assignee: EyePoint Pharmaceuticals, Inc.
• Original Assignee: pSivida US, Inc
• Inventors: Chou, Kang-Jye, Guo, Hong, Ashton, Paul, Shimizu, Robert W., Watson, David A.
• Primary Examiner(s): Richter, Johann R
• Assistant Examiner(s): SULLIVAN, DANIELLE D
• Application Number:
  US10/714,549
• Publication Number:
  US 20040176341A1
• Time in Patent Office: 4,002 Days
• Field of Search: 424/426, 424/425, 424/424, 424/423, 424/428
• US Class Current: 424/425
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209

Abstract

An injectable drug delivery device includes a core containing one or more drugs and one or more polymers. The core may be surrounded by one or more polymer outer layers (referred to herein as “coatings,” “skins,” or “outer layers”). In certain embodiments, the device is formed by extruding or otherwise preforming a polymeric skin for a drug core. The drug core may be co-extruded with the skin, or inserted into the skin after the skin has been extruded, and possibly cured. In other embodiments, the drug core may be coated with one or more polymer coatings. These techniques may be usefully applied to fabricate devices having a wide array of drug formulations and skins that can be selected to control the release rate profile and various other properties of the drugs in the drug core in a form suitable for injection using standard or non-standard gauge needles. The device may be formed by combining at least one polymer, at least one drug, and at least one liquid solvent to form a liquid suspension or solution wherein, upon injection, such suspension or solution under goes a phase change and forms a gel. The configuration may provide for controlled release of the drug(s) for an extended period.

Claims

1. A cylindrical drug delivery device shaped and sized for injection through a needle or cannula having a size from about 30 gauge to 23 gauge comprising:

a core including an effective amount of fluocinolone acetonide, wherein the core comprises a matrix of fluocinolone acetonide particles and one or more polymers;

a polymeric tube, impermeable to fluocinolone acetonide, longitudinally surrounding the core, the tube comprising polyimide;

at least one diffusion membrane, permeable or semi-permeable to the passage of fluocinolone acetonide, disposed at an end of the delivery device.

2. The device of claim 1 wherein at least one of the one or more polymers of the core is bioerodible.

3. The device of claim 1 wherein at least one of the one or more polymers of the core is bioerodible.

4. The device of claim 1 wherein at least one of the one or more polymers of the core is radiation curable.

5. The device of claim 1 wherein at least one of the one or more polymers of the core is heat curable.

6. The device of claim 1 wherein at least one of the one or more polymers of the core is evaporation curable.

7. The device of claim 1 wherein at least one of the one or more polymers of the core is curable by catalysis.

8. The device of claim 1 wherein the diffusion membrane further comprises at least one drug.

9. The device of claim 1 further comprising an anchor.

10. The device of claim 1 wherein the device is shaped and sized for at least one of periocular or intraocular injection.

11. The device of claim 1 further comprising an anchor for securing the device after injection.

12. The device of claim 1 wherein the device provides sustained release of fluocinolone acetonide when exposed to a biological medium.

13. The device of claim 1 wherein the core is completely covered by a combination of the polymeric tube and the diffusion membrane.

14. The device of claim 1 wherein the diffusion membrane is bioerodible.

15. The device of claim 14 wherein a release rate of fluocinolone acetonide is influenced by an erosion of the second polymeric skin.

16. The device of claim 14 wherein a release rate fluocinolone acetonide is independent of an erosion of the diffusion membrane.

17. The device of claim 13 wherein each of the core and the diffusion membrane is bioerodible.

18. The device of claim 13 wherein a release rate of fluocinolone acetonide is controlled by at least one of the permeability of the diffusion membrane to the at least one of the one or more drugs and a surface area of the core that is not covered by the polymeric tube.

19. The device of claim 13 wherein at least one of the polymeric tube and the diffusion membrane prevents direct interaction of biological fluids with the core.

20. The device of claim 13 wherein a release rate of fluocinolone acetonide is controlled by a surface area of the core.

21. The device of claim 13 wherein diffusion of fluocinolone acetonide through the core is not a rate-limiting step of release for the fluocinolone acetonide.

22. The device of claim 13 wherein diffusion of fluocinolone acetonide through the core is a rate-limiting step of release for the fluocinolone acetonide.

23. The device of claim 13 wherein dissolution of fluocinolone acetonide within the core is a rate-limiting step of release for the fluocinolone acetonide.

24. The device of claim 13 wherein the fluocinolone acetonide is more stable within the device than in a biological medium.

25. The device of claim 13 wherein the device provides increased stability of the fluocinolone acetonide to a curing process.

26. The device of claim 13 wherein the device provides increased stability of the fluocinolone acetonide to storage.

27. The device of claim 13 further comprising an anchor.

28. The device of claim 1 wherein the one or more polymers of the core comprise polyvinyl alcohol.

29. The device of claim 1 wherein the diffusion membrane comprises polyvinyl alcohol.

30. The device of claim 1 wherein each end of the device is covered by a diffusion membrane.

31. The device of claim 1 wherein one end of the device is sealed with a silicone adhesive.