Methods for manufacturing delivery devices and devices thereof

• US 20060029637A1
• Filed: 08/03/2005
• Published: 02/09/2006
• Est. Priority Date: 08/04/2004
• Status: Active Grant

• Current Assignee: Evonik Corporation
• Original Assignee: Evonik Corporation
• Inventors: Tice, Thomas R., Hudson, Bruce W., Tipton, Arthur J.
• Granted Patent: US 8,541,028 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

Described herein are methods for reducing and achieving the desired release of an agent from a delivery system. The desired release kinetics are achieved by exposing the surface of the delivery system with a fluid for a desired period of time.

Claims

1. A method for preparing a device comprising an agent, comprising

(a) admixing at least one polymer and at least one agent to produce an admixture;

(b) processing the admixture to produce a device of a desired shape, wherein the device comprises at least two exposed surfaces; and

(c) contacting the device with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer, wherein at least one exposed surface or least one part of at least one exposed surface of the device is not contacted with the fluid, and

wherein steps (a) and (b) do not involve the use of a solvent.

2. The method of claim 1, wherein at least two exposed surfaces of the device are not contacted with the fluid.

3. The method of claim 1, wherein two exposed surfaces of the device are not contacted with the fluid.

4. The method of claim 1, wherein the device comprises a rod, a fiber, a disc, a wafer, a bead, a ribbon, or a cylinder.

5. The method of claim 1, wherein the device comprises a rod comprising two ends and a longitudinal surface, wherein the ends of the rod are not contacted with the fluid, and wherein the longitudinal surface is contacted with the fluid.

6. The method of claim 1, wherein the device comprises a rod comprising two ends and a longitudinal surface, wherein after contacting the device with the fluid, at least one end of the rod is removed to expose an untreated end.

7. The method of claim 1, wherein the processing step comprises melt extruding, injection molding, compression molding, or roller compacting the admixture into a desired shape.

8. The method of claim 1, wherein the fluid comprises methylene chloride, chloroform, acetone, anisole, methyl acetate, N-methyl-2-pyrrolidone, hexafluoroisopropanol, tetrahydrofuran, dimethylsulfoxide, water, 2-pyrollidone, triethyl citrate, ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, Miglyol 810, isopropanol, ethanol, super critical carbon dioxide, acetonitrile, or a mixture thereof.

9. The method of claim 1, wherein the fluid comprises ethyl acetate.

10. The method of claim 1, wherein the fluid comprises a gas.

11. The method of claim 10, wherein the gas comprises nitrogen, a polyfluorochloro compound, water vapor, a vapor of an organic solvent, or a mixture thereof.

12. The method of claim 1, wherein the agent comprises a bioactive agent.

13. The method of claim 12, wherein the bioactive agent comprises a drug, an immunological agent, an antigen, a protein, a peptide, an oligonucleotide, or a mixture thereof.

14. The method of claim 1, wherein the agent comprises an adhesive, a pesticide, a fragrance, an antifoulant, a dye, a salt, an oil, an ink, a cosmetic, a catalyst, a detergent, a curing agent, a flavor, a fuel, a herbicide, a metal, a paint, a photographic agent, a biocide, a pigment, a plasticizer, a propellant, a stabilizer, a polymer additive, or any combination thereof.

15. The method of claim 1, wherein the polymer comprises a biodegradable polymer, wherein the biodegradable polymer comprises a poly(lactide), a poly(glycolide), a poly(lactide-co-glycolide), a poly(lactic acid), a poly(glycolic acid), a poly(lactic acid-co-glycolic acid), or a combination, blend, or copolymer thereof.

16. The method of claim 15, wherein the biodegradable polymer comprises a polymer formed from components comprising 40 to 100 mole % lactide and from 0 to 60 mole % glycolide.

17. The method of claim 15, wherein the biodegradable polymer comprises poly(lactide-co-glycolide), poly(lactide), or a combination, blend, or copolymer thereof.

18. The method of claim 1, wherein admixing step (a) comprises dry blending poly(lactide-co-glycolide), poly(lactide), or a combination, blend, or copolymer thereof, with a bioactive agent to produce an admixture, melt extruding the admixture to produce a rod, contacting the rod with ethyl acetate, and cutting the rod into one or more smaller rods having a predetermined length.

19. The method of claim 1, wherein the device is not a sphere.

20. The method of claim 1, wherein the device is not a microsphere or a microparticle.

32. A device produced by the method of claim 1.

21. A method for preparing a device comprising an agent, comprising

(a) admixing at least one polymer and at least one agent to produce an admixture;

(b) processing the admixture to produce a device of a desired shape; and

(c) contacting the device with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer,

wherein steps (a) and (b) do not involve the use of a solvent.

25. The method of claim 21, wherein the device is not a microsphere or a microparticle.

22. A method for preparing a device comprising at least one polymer and at least one agent, comprising contacting the device with the agent incorporated therein with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer.

26. The method of claim 22, wherein the device is not a microsphere or a microparticle.

23. A method for preparing a device comprising at least one polymer and at least one agent, comprising contacting the device with the agent incorporated therein with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer, wherein at least one exposed surface or least one part of at least one exposed surface of the device is not contacted with the fluid.

27. The method of claim 23, wherein the device is not a microsphere or a microparticle.

24. A method for preparing a device, comprising

(a) admixing at least one polymer and at least one agent to produce an admixture;

(b) processing the admixture to produce a device of a desired shape; and

(c) contacting the device with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer,

wherein steps (a) and (b) involve the use of a non-solvent for the polymer.

28. The method of claim 24, wherein the device is not a microsphere or a microparticle.

29. A method for producing a coated article, comprising

(a) coating the outer surface of the article with at least one polymer to produce the coated article;

and

(b) contacting the coated article with a sufficient amount of a fluid to change the surface morphology of at least part of the surface of the polymer.

30. The method of claim 29, wherein the article comprises a medical implant.

31. The method of claim 29, wherein the article comprises a stent, a suture, a surgical clip, a rod, a pin, an anchor, a mesh, a scaffold, a tissue-generating scaffold, a wound dressing, a membrane, an orthopedic device, a device for dermal application, or a medical electronic device.

33. A coated article produced by the method of claim 29.

34. A device comprising at least one polymer and at least one agent, wherein the agent is dispersed in the polymer, wherein the device comprises at least two exposed surfaces of the same polymer, wherein at least one of the exposed surfaces or least one part of at least one exposed surface has surface morphology different than the other exposed surface or surfaces.

35. The device of claim 34, wherein the device comprises a rod comprising two ends and a longitudinal surface, wherein the ends of the rod have a surface morphology that is different the surface morphology of the longitudinal surface.

36. An article comprising at least one first exposed surface and a polymer coating comprising a second exposed surface, wherein the polymer coating is connected to the first exposed surface of the article, wherein the morphology near the second exposed surface of at least part of the polymer coating is different than the morphology of the remaining polymer coating.