Extended release biodegradable ocular implants

• US 20050244467A1
• Filed: 04/30/2004
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Nivaggioli, Thierry, Lin, Qing, Shiah, Jane Guo
• Granted Patent: US 8,685,435 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

Biodegradable implants sized and suitable for implantation in an ocular region or site and methods for treating ocular conditions. The implants provide an extended release of an active agent at a therapeutically effective amount for a period of time between 50 days and one year, or longer.

Claims

1. A drug delivery system for treating an ocular condition, the drug delivery system comprising:

(a) at least one bioerodible implant suitable for insertion into an ocular region or site, the bioerodible implant comprising;

(i) an active agent, and;

(ii) a bioerodible polymer,

wherein the bioerodible implant can release a therapeutic level of the active agent into the ocular region or site for a period time between about 30 days and about 1 year.

2. The drug delivery system of claim 1, wherein the active agent is an anti-inflammatory agent.

3. The drug delivery system of claim 1, wherein the bioerodible polymer is a PLGA co-polymer.

4. The drug delivery system of claim 1, wherein the bioerodible implant has a weight between about 1 μ

g and about 100 mg.

5. The drug delivery system of claim 1, wherein the bioerodible implant has no dimension less than about 0.1 mm and no dimension greater than about 20 mm.

6. The drug delivery system of claim 1, wherein the drug delivery system comprises a plurality of bioerodible implants.

7. The drug delivery system of claim 1, wherein the active agent is substantially homogenously dispersed within the bioerodible polymer.

8. The drug delivery system of claim 1, wherein the active agent is associated with the bioerodible polymer in the form of particles of active agent and bioerodible polymer.

9. The drug delivery system of claim 1, wherein the drug delivery system comprises:

(a) a portion of the active agent substantially homogenously dispersed within a portion of the bioerodible polymer, and;

(b) a portion of the same or of a different active agent associated with a portion of same or of a different bioerodible polymer in the form of particles of active agent and the bioerodible polymer.

10. A drug delivery system for treating an ocular condition, the drug delivery system comprising:

(a) a bioerodible implant suitable for insertion into an ocular region or site, the bioerodible implant comprising;

(i) an active agent, and;

(ii) a bioerodible polymer,

wherein the bioerodible implant can release a therapeutic level of the active agent upon insertion into a posterior ocular region or site for a period time of at least about 40 days.

11. A drug delivery system for treating an ocular condition, the drug delivery system comprising:

(a) a plurality of bioerodible implants implantable in a posterior ocular region or site, each implant comprising;

(i) an active agent, and;

(ii) a bioerodible polymer,

wherein the plurality of bioerodible implants can substantially continuously release in vivo a therapeutic level of the active agent for a period time between about 5 days and about 1 year.

12. The drug delivery system of claim 11, wherein the drug delivery system comprises:

(a) a first implant with a first release characteristic, and;

(b) a second implant with a second release characteristic, wherein the first and second release characteristics differ.

13. The drug delivery system of claim 12, wherein the release profile of the drug delivery system corresponds to the sum of the first and second release profiles.

14. The drug delivery system of claim 11, wherein the drug delivery system comprises:

(a) a first implant with a first release characteristic,

(b) a second implant with a second release characteristic, and;

(c) a third implant with a third release characteristic.

15. The drug delivery system of claim 14, wherein the release profile of the drug delivery system corresponds to the sum of the first, second and third release profiles.

16. The drug delivery system of claim 11, wherein the drug delivery system comprises at least two different implants which have different bioerodible polymers.

17. The drug delivery system of claim 14 comprising first, second and third bioerodible implants, wherein

the first implant comprises a first polymer with a first average molecular weight;

the second implant comprises a second polymer with a second average molecular weight, and

the third implant comprises a third polymer with a third average molecular weight.

18. The drug delivery system of claim 11, wherein the active agent is an anti-inflammatory compound.

19. The drug delivery system of claim 11, wherein the active agent is an anti-angiogenesis compound.

20. A drug delivery system for treating an ocular condition comprising;

(a) a plurality of bioerodible implants implantable in a posterior ocular region, each implant comprising

(i) an anti-inflammatory drug, and;

(ii) a bioerodible polymer,

wherein the plurality of bioerodible implants can substantially continuously release the anti-inflammatory drug at a level of at least about a 10 ng/ml dexamethasone equivalent for a period of between 5 days and 1 year.

21. An extended release bioerodible implant for treating an ocular condition, the bioerodible implant being made by:

(a) blending an active agent and a first bioerodible polymer to form a first solid material;

(b) breaking the first solid material into particles;

(c) blending the particles with the active agent and a second bioerodible polymer, to thereby form a bioerodible implant, wherein the bioerodible implant can release a therapeutic level of the active agent at a substantially continuous rate for a period time between about 50 days and about 1 year.

22. A bioerodible implant for treating an ocular condition, the bioerodible implant being made by:

(a) blending a steroidal anti-inflammatory drug and a first bioerodible polymer to form a first solid material;

(b) breaking the solid material into particles;

(c) blending the particles with the steroidal anti-inflammatory drug and a second bioerodible polymer to form a bioerodible implant, wherein the bioerodible implant can release a therapeutic level of the active agent at a substantially continuous rate for a period time between about 50 days and about 1 year.

23. The bioerodible implant of claim 22 wherein the implant can substantially continuously release the steroidal anti-inflammatory drug at a dexamethasone equivalent level corresponding to at least 10 ng/ml for a period of at between 50 days and one year.

24. The bioerodible implant of claim 22 wherein the implant can continuously release the steroidal anti-inflammatory drug at a dexamethasone equivalent corresponding to at least 50 ng/ml for a period of at least about 50 days.

25. A bioerodible implant for treating an ocular condition, comprising:

(a) a dispersion comprising an active agent dispersed with a first bioerodible polymer,

(b) a particle comprising the active agent and a second bioerodible polymer,

wherein the particle has an active agent release characteristic which differs from the active agent release characteristic of the dispersion.

26. The bioerodible implant of claim 25 wherein the implant can substantially continuously release the active agent at a level corresponding to at least 10 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

27. The bioerodible implant of claim 25 wherein the implant can substantially continuously release the active agent at a level corresponding to at least 50 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

28. A bioerodible implant for treating an inflammation-mediated condition of the eye, the implant being made by:

(a) blending a first active agent and a first bioerodible polymer to thereby form a first active agent polymer mixture;

(b) blending a second active agent and a second bioerodible polymer to thereby form a second active agent polymer mixture;

(c) co-extruding the first and second active agent polymer mixtures to thereby form a bioerodible implant containing first and second regions, the first region containing the first active agent polymer mixture, and the second region containing the second active agent polymer mixture, wherein first and second regions have different active agent release characteristics.

29. The bioerodible implant of claim 28, wherein the first active agent and the second active agent are the same active agent.

30. The bioerodible implant of claim 28, wherein the first active agent and the second active agent are different active agents.

31. The bioerodible implant of claim 28, wherein the first polymer and the second polymer are the same polymer.

32. The bioerodible implant of claim 28, wherein the first polymer and the second polymer are different polymers.

33. The bioerodible implant of claim 28 wherein the implant can substantially continuously releases active agent at levels corresponding to at least 10 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

34. The bioerodible implant of claim 28 wherein the implant can substantially continuously releases active agent at levels corresponding to at least 50 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

35. A bioerodible implant for treating a posterior ocular condition, bioerodible implant being made by:

(a) blending a first active agent and a first bioerodible polymer to thereby form a first active agent polymer mixture;

(b) co-extruding the first active agent polymer mixture with a second polymer to thereby form a bioerodible implant containing first and second regions, the first region containing the first active agent polymer mixture, and the second region containing the second polymer mixture.

36. The bioerodible implant of claim 35, wherein where the first polymer and the second polymer are the same polymer.

37. The bioerodible implant of claim 35, wherein the first polymer and the second polymer are different polymers.

38. A bioerodible implant for treating a posterior ocular condition, the bioerodible implant comprising:

(a) a first region containing a first mixture of an active agent and a first bioerodible polymer, and;

(b) a second region containing a second mixture of the active agent and a second bioerodible polymer,

wherein the first and second regions have different active agent release characteristics.

39. The bioerodible implant of claim 38 wherein the implant can substantially continuously releases active agent at levels corresponding to at least 10 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

40. The bioerodible implant of claim 38 wherein the implant can substantially continuously releases active agent at levels corresponding to at least 50 ng/ml of dexamethasone or dexamethasone equivalent for a period of at least about 50 days.

41. A method for treating an ocular condition, the method comprising implanting into an ocular region or site a drug delivery system comprising:

(a) at least one bioerodible implant suitable for insertion into an ocular region or site, the bioerodible implant comprising;

(i) an active agent, and;

(ii) a bioerodible polymer,

wherein the bioerodible implant can release a therapeutic level of the active agent at a substantially continuous rate upon insertion into an ocular region or site for a period time between about 50 days and about 1 year.