Zero-order prolonged release coaxial implants

• US 8,263,108 B2
• Filed: 06/21/2002
• Issued: 09/11/2012
• Est. Priority Date: 06/22/2001
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Gibson, John W., Tipton, Arthur J., Holl, Richard J., Meador, Stacey
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US10/177,997
• Publication Number:
  US 20030007992A1
• Time in Patent Office: 3,735 Days
• Field of Search: None
• US Class Current: 424/426
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• 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: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

A coaxial implant has been developed using entirely biodegradable polymeric materials. As referred to herein, a coaxial implant is a device having a core containing drug, surrounded by a semi-permeable membrane that controls the rate of release of material from the core. The device is formed by extrusion, using a pre-milling and extruding step to maximize uniformity of drug dispersion within the polymeric material. In one embodiment, the polymer is processed to yield a semi-crystalline polymer, rather than an amorphous polymer. The core containing the drug and the polymer membrane(s) can be the same or different polymer. The polymer can be the same or different composition (i.e., both polycaprolactone, or both poly(lactide-co-glycolide) of different monomer ratios, or polycaprolactone outside of a core of poly(lactide)), of the same or different molecular weights, and of the same or different chemical structure (i.e., crystalline, semi-crystalline or amorphous). The core acts as a reservoir of drug, which partitions from the core polymer to form a saturated solution of at least 10% drug at the polymer membrane.

Claims

1. A biodegradable coaxial implant in the form of a rod comprising a core comprising active agent to be delivered and a rate-controlling membrane, wherein the rate controlling membrane comprises a polymer selected from the group consisting of polyhydroxyacids, polyanhydrides, polyorthoesters, polyetheresters, polycaprolactone, polyesteramides, polyphosphazenes, polycarbonates, and copolymers and blends thereof, wherein the implant exhibits sustained near zero-order release of an effective amount of the active agent over a period of at least 30 days.

3. The implant of claim 1 wherein the membrane is a macroporous membrane.

4. The implant of claim 1 wherein the membrane is a semi-permeable membrane.

5. The implant of claim 1 wherein the core is formed by dry blending of active agent and polymer, followed by extrusion.

6. The implant of claim 1 wherein the core is formed by a double extrusion process.

7. The implant of claim 1 wherein the core is a liquid.

8. The implant of claim 1 wherein the core is pure drug.

10. The implant of claim 1 wherein the implant comprises active agent in or abutting the membrane.

11. The implant of claim 1 wherein the implant is fabricated as part of a device selected from the group of a matrix, prosthetic, graft, or coating.

12. The implant of claim 1 wherein the core composition further comprises concentric layers having different compositions.

13. The implant of claim 1 wherein the core comprises excipient.

14. The implant of claim 1 wherein the rate-controlling membrane comprises pore forming agents.

15. The implant of claim 1 wherein the rate controlling membrane comprises a polymer selected from the group consisting of polyhydroxyacid, caprolactone, and copolymers thereof.

16. The implant of claim 1 wherein the implant has sealed ends.

17. The implant of claim 1 wherein the implant is further processed by post-extrusion drawing or annealing.

18. The implant of claim 1 wherein the active agent is water soluble.

19. The implant of claim 1 wherein the active agent is a protein or peptide.

20. The implant of claim 1 wherein the core contains a non-polymeric, water-insoluble liquid and an active agent.

21. The implant of claim 1 formed by filling a preformed membrane with a liquid, drug-containing formulation.

22. A method of administering a drug to a patient comprising implanting the implant of claim 1 in the patient.

23. The implant of claim 1, wherein the cross-sectional geometry of the rod is selected from the group consisting of ellipsoid, circle, lobe, square, and triangle.

2. A biodegradable coaxial implant in the form of a rod comprising a core comprising active agent to be delivered and a rate-controlling membrane, wherein the rate controlling membrane comprises a polymer selected from the group consisting of polyhydroxyacids, polyanhydrides, polyorthoesters, polyetheresters, polycaprolactone, polyesteramides, polyphosphazenes, polycarbonates, and copolymers and blends thereof, wherein the core of the implant is formed of a crystalline, semicrystalline, or amorphous biodegradable polymer having active agent incorporated therein and, wherein the implant exhibits sustained near zero-order release of an effective amount of the active agent over a period of at least 30 days.

9. The implant of claim 2 wherein the polymer forming the membrane and the core is the same polymer.