Subdermally implantable device

• US 5,660,848 A
• Filed: 11/02/1994
• Issued: 08/26/1997
• Est. Priority Date: 11/02/1994
• Status: Expired due to Term

• Current Assignee: The Population Counsil Incorporated
• Original Assignee: The Population Coucil Center For Biomedical Research
• Inventors: Moo-Young, Alfred Joseph
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/333,279
• Time in Patent Office: 1,028 Days
• Field of Search: 424/422, 424/423, 424/424, 424/425, 514/772.3, 514/781
• US Class Current: 424/425
• 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 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04

Abstract

Disclosed is a subdermally implantable drug-delivery device, which contains: a central core extending in an axial direction and having an outer surface and opposing ends, which core includes a matrix of a pharmaceutically effective amount of a subdermally administrable drug substantially uniformly dispersed in a polymeric base material; an intermediate polymeric layer overlying the outer surface of the central core; and an outer polymeric layer overlying the intermediate layer, wherein the intermediate layer controls the rate of diffusion of the drug from the central core to the outer layer. In preferred embodiments, the subdermally administrable drug is a contraceptive agent such as the 16-methylene-17-α-acetoxy-19-norprogesterone progestin; the polymeric base material and the outer polymeric layer each contain a polydimethylsiloxane such as Silastic®; and the intermediate layer contains a porous material such as cellulose. The devices provide for the substantially zero-order release of the drug for their intended lifetime without initial overdosing of the drug.

Claims

1. A subdermally implantable drug delivery device, comprising:

a central core extending in an axial direction and having an outer surface and opposing ends, said core including a matrix of a pharmaceutically effective amount of a subdermally administrable drug substantially uniformly dispersed in a polymeric base material;

an intermediate layer comprising a porous polymeric material overlying said outer surface of said central core; and

an outer polymeric layer overlying said intermediate layer, wherein said intermediate layer controls the rate of diffusion of said drug from said central core to said outer layer.

2. A device according to claim 1, wherein said polymeric base material comprises an ethylene/vinyl acetate copolymer.

3. A device according to claim 1, wherein said polymeric base material comprises a silicone rubber.

4. A device according to claim 3, wherein said silicone rubber comprises a polydimethylsiloxane.

5. A device according to claim 1, wherein said subdermally administrable drug is a contraceptive agent.

6. A device according to claim 5, wherein said contraceptive agent is a progestin.

7. A device according to claim 6, wherein said progestin is 16-methylene-17-α

-acetoxy-19-norprogesterone.

8. A device according to claim 6, wherein said progestin is 3-keto-desogestrel.

9. A device according to claim 5, wherein said polymeric base material and said contraceptive agent are present in said central core in a weight ratio of polymeric base material to contraceptive agent of from about 0.67:

1 to about 3;

1.

10. A device according to claim 9, wherein the ratio is from about 1:

1 to about 4.5;

5.5.

11. A device according to claim 1, wherein said porous material comprises a cellulosic material.

12. A device according to claim 1, wherein said porous material has pore sizes from about 0.0025 microns to about 0.0050 microns.

13. A device according to claim 1, wherein said outer layer comprises a silicone rubber.

14. A device according to claim 13, wherein said silicone rubber is a polysiloxane.

15. A device according to claim 1, further comprising sealing means cooperating with said outer layer to fully encapsulate said central core and said intermediate layer.

16. A device according to claim 15, wherein said outer layer has opposing ends extending axially beyond said opposing ends of said central core to define cavities adjacent said opposing ends of said central core, and said sealing means comprises adhesive disposed in said cavities.

17. A device according to claim 16, wherein said sealing means further comprises a layer of polytetrafluoroethylene disposed between said opposing end of said central core and said adhesive in each of said cavities.

18. A device according to claim 1, which is substantially cylindrical in shape.

19. A device according to claim 1, having an axial length of from about 4.2 cm to about 4.6 cm.

20. A device according to claim 1, having a diameter of from about 2.5 mm to about 2.7 mm.

21. A device according to claim 1, wherein said central core has an axial length of from about 3.8 cm to about 4.2 cm.

22. A device according to claim 1, wherein said central core has a diameter of from about 2.0 mm to about 2.2 mm.

23. A device according to claim 1, wherein said intermediate layer has a thickness of from about 0.05 mm to about 0.10 mm.

24. A device according to claim 1, wherein said intermediate layer comprise cellulose.

25. A device according to claim 24, wherein said cellulose is regenerate cellulose.

26. A subdermally implantable drug delivery device, comprising:

a central core extending in an axial direction and having an outer surface and opposing ends, said core including a matrix of a pharmaceutically effective amount of a contraceptive agent substantially uniformly dispersed in a first polydimethylsiloxane elastomeric material;

an intermediate cellulosic layer overlying said outer surface of said central core; and

an outer layer of a second polydimethylsiloxane elastomeric material overlying said intermediate cellulosic layer, wherein said intermediate cellulosic layer controls rate of diffusion of said contraceptive agent from said central core to said outer layer.

27. A device according to claim 26, herein said contraceptive agent comprises 16-methylene-17-α

-acetoxy-19-norprogesterone.

28. A device according to claim 27, wherein said intermediate cellulosic layer comprises cellulose.

29. A device according to claim 28, wherein said cellulose comprises regenerated cellulose.