SUSTAINED RELEASE DELIVERY DEVICES

• US 20110238036A1
• Filed: 12/22/2010
• Published: 09/29/2011
• Est. Priority Date: 12/23/2009
• Status: Abandoned Application

• Current Assignee: pSivida US, Inc
• Original Assignee: pSivida US, Inc
• Inventors: Ashton, Paul
• Application Number:
  US12/975,696
• Publication Number:
  US 20110238036A1
• Time in Patent Office: Days
• US Class Current: 604/506
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 9/0048 Eye, e.g. artificial tears
• 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 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

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.

Claims

1. A drug delivery device shaped and sized for injection comprising:

a core including one or more drugs; and

a polymeric skin at least partially surrounding the core, the skin comprising a first one or more polymers.

2. The device of claim 1, wherein the core comprises a matrix of the one or more drugs and a second one or more polymers.

3. The device of claim 2, wherein at least one of the second one or more polymers is bioerodible.

4. The device of claim 2, wherein the second one or more polymers comprises at least one of poly(vinyl acetate) (PVAC), poly(caprolactone) (PCL), polyethylene glycol (PEG), poly(dl-lactide-co-glycolide) (PLGA), ethylene vinyl acetate polymer (EVA), poly(vinyl alcohol) (PVA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof.

5. The device of claim 1, wherein the one or more drugs includes at least one of a codrug or a prodrug.

6. The device of claim 1, wherein the core comprises a biocompatible gelling formulation.

7. The device of claims 1, wherein the one or more drugs includes a steroid.

8. The device of claim 7, wherein the steroid comprises at least one of loteprednol etabonate, triamcinolone acetonide (TA), fluocinolone acetonide, or anacortave acetate.

9. The device of claim 1, wherein at least one of the one or more drugs comprises an anti-metabolite.

10. The device of claim 9, wherein the anti-metabolite comprises 5-fluorouracil (5-FU).

11. The device of claim 1, wherein at least one of the one or more drugs comprises an adrenergic agent.

12. The device of claim 11, wherein the adrenergic agent comprises brimonidine.

13. The device of claim 1, wherein at least one of the one or more drugs comprises a carbonic anhydrase inhibitor.

14. The device of claim 13, wherein the carbonic anhydrase inhibitor comprises at least one of acetazolamide, methazolamide, ethoxzolamide, dichlorphenamide, dorzolamide, or brinzolamide.

15. The device of claim 1, wherein at least one of the one or more drugs comprises an antiviral agent.

16. The device of claim 15, wherein the antiviral agent comprises neviripine.

17. The device of claim 1 wherein the polymeric skin is one of impermeable, semi-permeable, or permeable to at least one of the one or more drugs.

18. The device of claims 1, wherein the polymeric skin comprises at least one of PVAC, PCL, PEG, PLGA, EVA, PVA, PLA, PGA, polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof.

19. The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is bioerodible.

20. The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is radiation curable.

21. The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is heat curable.

22. The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is evaporation curable.

23. The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is curable by catalyzation.

24. The device of claim 1, wherein the polymeric skin further comprises at least one drug.

25. The device of claim 1, further comprising an anchor, wherein the device is shaped and sized for injection through at least one of a needle having a size from about 30 gauge to about 15 gauge or a cannula having a size from about 30 gauge to about 15 gauge.

26. The device of claim 1, wherein the device is shaped and sized for injection through at least one of a cannula having a size from about 30 gauge to about 15 gauge or a needle having a size from about 30 gauge to about 15 gauge.

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

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

29. The device of claim 1, wherein the device provides sustained release of the one or more drugs when exposed to a biological medium.

30. The device of claim 2, further comprising a second polymeric skin.

31. The device of claim 30, wherein the polymeric skin has a different permeability to the one or more drugs than the second polymeric skin, and the core is completely covered by a combination of the polymeric skin and the second polymeric skin.

32. The device of claim 30, wherein at least one of the polymeric skin, or the second polymeric skin is bioerodible.

33. The device of claim 32, wherein a release rate of at least one of the one or more drugs is influenced by an erosion of at least one of the polymeric skin or the second polymeric skin.

34. The device of claim 32, wherein a release rate of at least one of the one or more drugs is independent of an erosion of at least one of the polymeric skin or the second polymeric skin.

35. The device of claim 31, wherein each of the core, the polymeric skin, and the second polymeric skin is bioerodible.

36. The device of claim 31, wherein a release rate of at least one of the one or more drugs is controlled by at least one of the permeability of the second polymeric skin 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 skin.

37. The device of claim 31, wherein at least one of the polymeric skin and the second polymeric skin prevent direct interaction of biological fluids with the core.

38. The device of claim 31, wherein a release rate of at least one of the one or more drugs is controlled by a surface area of the core.

39. The device of claim 31, wherein a release rate of at least one of the one or more drugs is not substantially influenced by diffusion of the at least one drug through the core.

40. The device of claim 31, wherein a release rate of at least one of the one or more drugs is significantly influenced by diffusion of the at least one drug through the core.

41. The device of claim 31, wherein a release rate of at least one of the one or more drugs is significantly influenced by a solubility of the at least one drug within the core.

42. The device of claim 31, wherein at least one of the one or more drugs is more stable within the device than in a biological medium.

43. The device of claim 31, wherein the device provides increased stability of at least one of the one or more drugs to a curing process.

44. The device of claim 31, wherein the device provides increased stability of at least one of the one or more drugs to storage.

45. A device of any one of claims 1 to 44, wherein the device releases the drug at a rate of less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, or even less than about 0.1 μ

g/day.

46. A method for treating diabetic macular edema, comprising administering a device of any one of claims 1 to 45.

47. The method of claim 46, wherein the drug is released at a rate of less than about 0.4 μ

g/day steadily and continuously for a period of at least six months.

48. The method of claim 47, wherein the method comprises treating said diabetic macular edema with fewer side effects.

49. The method of claim 48, wherein said side effects include increased IOP.

50. A drug delivery device comprising:

a drug core, preferably comprising a glucocorticoid, such as fluocinolone acetonide;

a polymer tube, preferably a tube impermeable to the passage of drug, such as a tube comprising polyimide; and

an outer layer covering at least one end, preferably covering both ends of the device and a portion of the tube, wherein the outer layer is permeable to the passage of drug;

wherein the device releases the drug at a rate of less than about 0.5, about 0.4, about 0.3, about 0.2, or even less than about 0.1 μ

g/day.

51. A device of claim 50, wherein the outer layer comprises polyvinyl alcohol.

52. A device of claim 50 or 51, wherein the device releases the drug at a substantially continuous release rate.

53. A method for the treatment of diabetic macular edema, comprising administering a device of any one of claims 50-52.

54. A method for treating an eye disease or disorder with fewer side effects, comprising administering a drug to an eye of a patient in need thereof daily for a period of at least 3 months, wherein said drug is administered at a release rate of less than or equal to 0.4 μ

g/day to treat said disease or disorder without causing a significant increase in IOP in a substantial percentage of treated patients.

55. The method of claim 54, wherein the disease or disorder of the eye is macular edema or macular degeneration.

56. The method of claim 54 or 55, wherein said drug is administered at a release rate of less than or equal to 0.3 μ

g/day, 0.2 μ

g/day, or 0.1 μ

g/day.

57. The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 20% of treated patients.

58. The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 10% of treated patients.

59. The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 5% of treated patients.

60. The method of any of claims 54-56, wherein increase in IOP occurs at a low enough frequency as to be considered a rare event associated with treatment.

61. A method for decreasing excess foveal thickness in a patient in need thereof, comprising administering a drug to an eye of said patient for a period of at least 3 months, wherein said drug is administered at a release rate of less than or equal to 0.4 μ

g/day to decrease excess foveal thickness.