Processes for forming a drug delivery device

• US 20040009222A1
• Filed: 05/02/2003
• Published: 01/15/2004
• Est. Priority Date: 05/07/2002
• Status: Abandoned Application

• Current Assignee: Control Delivery Systems Inc. (EyePoint Pharmaceuticals, Inc.)
• Original Assignee: Control Delivery Systems Inc. (EyePoint Pharmaceuticals, Inc.)
• Inventors: Guo, Hong, Ashton, Paul, Shimizu, Robert W., Chou, Kang-Jye
• Application Number:
  US10/428,214
• Publication Number:
  US 20040009222A1
• Time in Patent Office: Days
• US Class Current: 424/471
• 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

A drug delivery device can, in whole or in part, be formed by co-extruding a drug core and an outer tube. The outer tube may be permeable, semi-permeable, or impermeable to the drug. The drug core may include a polymer matrix which does not significantly affect the release rate of the drug. The outer tube, the polymer matrix of the drug core, or both may be bioerodible. The co-extruded product can be segmented into drug delivery devices. The devices may be left uncoated so that their respective ends are open, or the devices may be coated with, for example, a layer that is permeable to the drug, semi-permeable to the drug, or bioerodible.

Claims

1. A method of making a drug delivery device comprising co-extruding an inner drug-containing core and at least one outer polymeric skin that at least partially surrounds the core.

2. The method of claim 1, wherein the device is at least one of insertable, injectable, or implantable.

3. The method of claim 1, wherein the inner drug-containing core comprises a mixture of at least one drug and at least one polymer.

4. The method of claim 3, wherein the polymer of the inner drug-containing core is bioerodible.

5. The method of claim 3, wherein the at least one drug and the at least one polymer are admixed in powder form.

6. The method of claim 1, wherein the device includes at least one of a codrug or a prodrug.

7. The method of claim 1, wherein the inner drug core comprises a steroid.

8. The method of claim 7, wherein the steroid includes at least one of flucinolone acetonide (FA), loteprednol etabonate, or triamcinolone acetonide (TA).

9. The method of claim 1, wherein at least one of the inner drug core or the at least one outer polymeric skin comprises an anti-metabolite.

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

11. The method of claim 1, wherein the outer polymeric skin is one of impermeable, semi-permeable, or permeable to a drug disposed within the inner drug-containing core.

12. The method of claim 1, wherein the outer polymeric skin comprises at least one of polycaprolactone (PCL), an ethylene/vinyl acetate copolymer (EVA), polyalkyl cyanoacralate, polyurethane, a nylon, or poly(dl-lactide-co-glycolide) (PLGA).

13. The method of claim 1, wherein the inner drug-containing core comprises FA in admixture with poly(vinyl acetate) (PVAC), PCL, PEG or PLGA.

14. The method of claim 1, wherein the outer polymeric skin is bioerodible.

15. The method of claim 14, wherein the inner drug-containing core comprises a bioerodible polymer.

16. The method of claim 1, wherein the outer polymeric skin is radiation curable and the method further comprises applying radiation to the co-extruded drug delivery device.

17. The method of claim 1, wherein the outer polymeric skin comprises at least one drug.

18. The method according to claim 17, wherein the at least one drug comprises TA.

19. The method of claim 18, wherein the inner drug-containing core comprises 5-FU.

20. The method of claim 1, wherein the inner drug-containing core comprises 5-FU.

21. A method of making a drug delivery device comprising:

(a) forwarding a polymeric material to a first extrusion device;

(b) forwarding a drug to a second extrusion device;

(c) co-extruding a mass including the polymeric material and the drug; and

(d) forming the mass into at least one co-extruded drug delivery device which comprises a core including the drug and an outer layer including the polymeric material.

22. The method of claim 21, wherein the drug forwarded to the second extrusion device is in admixture with at least one polymer.

23. The method of claim 22, wherein the drug and the at least one polymer are admixed in powder form.

24. The method of claim 21, further comprising forwarding more than one drug to the second extrusion device.

25. The method of claim 21 wherein the polymeric material is one of impermeable, semi-permeable, or permeable to the drug.

26. The method of claim 21, wherein the polymeric material is bioerodible.

27. The method of claim 22, wherein the admixture with at least one polymer is bioerodible.

28. The method of claim 27, wherein the polymeric material is bioerodible.

29. The method of claim 21, wherein the polymeric material is radiation curable and the method further comprises applying radiation to the co-extruded drug delivery device.

30. The method of claim 21, wherein the co-extruded drug delivery device is in a tubular form.

31. The method of claim 21, further comprising segmenting the tubular form into a plurality of shorter products.

32. The method of claim 31, further comprising coating the plurality of shorter products with one or more layers including at least one of a layer that is permeable to the drug, a layer that is semi-permeable to the drug, and a layer that is bioerodible.

33. The method of claim 21, wherein the polymeric material includes at least one of PCL, PLGA or an EVA.

34. The method of claim 21, wherein the drug includes a steroid.

35. The method of claim 34, wherein the steroid includes at least one of FA or TA.

36. The method of claim 21, wherein the drug includes an anti-metabolite.

37. The method of claim 34, wherein the anti-metabolite is 5-FU.

38. The method of claim 37, wherein the polymeric material includes TA.

39. The method of claim 21, wherein the polymeric material includes TA.

40. The method of claim 21, wherein the drug is FA in admixture with at least one of PCL, PLGA or PVAC.

41. The method of claim 21, wherein the polymeric material includes at least one of PCL, PLGA or an EVA and the drug includes FA in admixture with at least one of PCL, PLGA or PVAC.

42. The method of claim 21, wherein the polymeric material includes at least one drug.

43. A device for fabricating an implantable drug delivery device comprising:

(a) a first extruder for extruding a core, wherein the core includes at least one drug; and

(b) a second extruder for extruding a skin, wherein the skin is disposed about the core to form a co-extruded material, and wherein the skin has at least one of a permeability or an erodibility selected to control the release rate of the drug in a device formed from a segment of the co-extruded material.

44. The device of claim 43, further comprising a segmenting station that separates the co-extruded material into a plurality of segments.

45. The device of claim 43, further comprising a curing station that at least partially cures the co-extruded material.