Drug delivery devices comprising biodegradable protein for the controlled release of pharmacologically active agents and method of making the drug delivery devices

• US 6,342,250 B1
• Filed: 09/25/1998
• Issued: 01/29/2002
• Est. Priority Date: 09/25/1997
• Status: Expired due to Term

• Current Assignee: PetVivo Holdings, Inc.
• Original Assignee: Gel-Del Technologies, Inc. (PetVivo Holdings, Inc.)
• Inventors: Masters, David B.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/160,421
• Time in Patent Office: 1,222 Days
• Field of Search: 424/486, 424/484, 424/464-465, 424/468, 424/489, 424/400, 424/443
• US Class Current: 424/484
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

The present invention relates to an improved method of making drug delivery devices for the controlled release of pharmacologically active agents and further, to drug delivery devices made by such method. More specifically, the present invention relates to a method of forming a film comprising one or more biodegradable polymeric materials, one or more pharmacologically active agents, and one or more biocompatible solvents. The film is then partially dried, rolled or otherwise shaped, and then compressed. In this manner, the amount of pharmacologically active agent(s) that can be incorporated into the drug delivery device is increased and the pharmacologically active agent(s) is/are substantially homogeneously distributed throughout the drug delivery device. As a result, the release characteristics of the pharmacologically active agent from the drug delivery device are enhanced.

Claims

1. A method of making a solvated drug delivery device, comprising the steps of:

(a) preparing a coatable composition comprising one or more biodegradable polymeric materials, one or more pharmacologically active agents, and one or more biocompatible solvents;

(b) coating the composition to form a film;

(c) partially drying the coated film until the coated film can be formed into a cohesive body;

(d) forming said cohesive body; and

(e) compressing the cohesive body to form a drug delivery device.

2. The method of claim 1, wherein the biodegradable polymeric material comprises a biodegradable protein.

3. The method of claim 2, wherein the biodegradable protein comprises a naturally occurring protein.

4. The method of claim 3, wherein the naturally occurring protein comprises elastin.

5. The method of claim 2, wherein the biodegradable protein comprises a genetically engineered protein.

6. The method of claim 5, wherein the genetically engineered protein comprises silk-like blocks and elastin-like blocks.

7. The method of claim 3, wherein the drug delivery device further comprises an additive to enhance the release characteristics of the pharmacologically active agent.

8. The method of claim 7, wherein the additive comprises one or more fatty acid monomers.

9. The method of claim 8, wherein the fatty acid monomers comprise an erucic dimer and sebacic acid.

10. The method of claim 9, wherein the ratio of fatty acid dimer to sabacic acid is 1:

4 based upon weight.

11. The method of claim 10, wherein the biodegradable polymeric material comprises a genetically engineered protein comprising silklike blocks and elastinlike blocks and wherein the ratio of the genetically engineered protein to the fatty acid dimer:

sabacic acid copolymer is about 2;

1, based upon weight.

12. The method of claim 1, wherein the cohesive body is compressed at a pressure of from about 100 psi to about 30,000 psi for a time period of from about 10 seconds to about 48 hours.

13. The method of claim 12, wherein the cohesive body is compressed at a pressure of from about 1000 psi to about 4000 psi for a time period of from about 1 minute to about 60 minutes.

14. The method of claim 1, wherein the cohesive body is compressed into the form of a cylinder.

15. The method of claim 14, wherein the cylinder is subsequently cut into discs.

16. The method of claim 1, wherein the pharmacologically active agent comprises a corticosteroid.

17. The method of claim 16, wherein the pharmacologically active agent comprises dexamethasone.

18. The method of claim 1, wherein the pharmacologically active agent comprises a neurotoxin.

19. The method of claim 20, wherein the neurotoxin is capsaicin.

20. The method of claim 1, wherein the pharmacologically active agent comprises an opioid analgesic.

21. The method of claim 20, wherein opioid analgesic comprises sufentanil.

22. The method of claim 1, wherein the pharmacologically active agent is a local anesthetic.

23. The method of claim 22, wherein the local anesthetic comprises bupivacaine, lidocaine, or a combination thereof.

24. The method of claim 1, wherein the pharmacologically active agent comprises an enzyme.

25. The method of claim 24, wherein the coatable composition further comprises an amount of an enzyme substrate.

26. The method of claim 1, wherein the drug delivery device contains a second, migration-vulnerable drug delivery device that incorporates the pharmacologically active agent.

27. The method of claim 26, wherein the migration-vulnerable drug delivery device comprises a plurality of lipospheres homogeneously dispersed within the drug delivery device.

28. The method of claim 27, wherein the migration-vulnerable drug delivery device comprises a plurality of microspheres homogeneously dispersed within the drug delivery device.

29. The method of claim 1, wherein the pharmacologically active agent is substantially homogeneously distributed within the drug delivery device.

30. The method of claim 1, wherein the biodegradable polymeric material comprises at least one polymeric material that degrades quickly and at least one polymeric material that degrades slowly relative to one another.

31. The method of claim 1, wherein the coated film is dried until the solvent content is approximately 50% to 70%.

32. The method of claim 1, wherein the drug delivery device includes a solvent content of approximately 30% to 60%.

33. The method of claim 32, wherein the drug delivery device includes a solvent content of approximately 40% to 50%.