BIODEGRADABLE DRUG DELIVERY SYSTEM

• US 20080292679A1
• Filed: 05/24/2007
• Published: 11/27/2008
• Est. Priority Date: 05/24/2007
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Burke, James A., Robinson, Michael R., Lyons, Robert T.
• Granted Patent: US 8,231,892 B2
• Time in Patent Office: Days
• US Class Current: 424/428
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4436 containing a heterocyclic ring having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 38/13 Cyclosporins
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• 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: C07K 16/18 against material from animals or humans

Abstract

A drug delivery system (DDS) comprised of segmented biodegradable implants sized and suitable for implantation in an ocular region or site and methods for treating ocular conditions. The segmented 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, and permit the DDS to have segments that possess individual and different drug release characteristics.

Claims

1. A drug delivery system for treating an ocular condition, the drug delivery system comprising a bioerodible implant having a plurality of segments, wherein:

a) each of the segments comprises (i) an active agent and (ii) a bioerodible polymer;

b) at least some of the segments have drug release characteristics different from other segments; and

c) the segments are joined together in a manner to permit separation from each other in situ into individual segments following intraocular implantation of the drug delivery system into a patient.

5. The drug delivery system according to claim 1, wherein the bioerodible polymer comprises at least one member selected from the group consisting of poly(lactide) polymers and poly(lactide-co-glycolide) copolymers.

6. The drug delivery system according to claim 1, wherein the implants further comprise at least one excipient that modifies the erosion characteristics of the bioerodible polymer.

7. The drug delivery system according to claim 6, wherein the excipient is a member selected from the group consisting of long chain fatty alcohols, cholesterol, and high molecular weight polyethylene glycol polymers.

8. The drug delivery system according to claim 6, wherein the bioerodible polymer comprises a poly(D,L-lactide-co-glycolide) copolymer with a monomer ratio in the range of 50:

50 to 85;

15.

9. The drug delivery system according to any one of claim 1, wherein at least one of the segments releases all active ingredient within one week of implantation and at least one of the segments begins releasing the active ingredient after one week post-implantation.

10. The drug delivery system according to claim 9, wherein at least one of the segments begins releasing active ingredient at 12 weeks post-implantation.

11. The drug delivery system according to any one of claim 1, wherein at least one of the segments releases the active ingredient from 3 to 6 months post-implantation.

12. The drug delivery system according to claim 1, wherein active ingredient is released from one of the segments within the first week after implantation, but no drug is released from any of the segments for some period of time after the first week post-implantation.

13. The drug delivery system according to claim 1, wherein at least some of the segments comprise a first active ingredient and other of the segments comprise a second active ingredient.

14. The drug delivery system according to claim 1, wherein each of the segments has drug release characteristics different from all of the other of the segments that comprise the implant.

15. The drug delivery system according to claim 1, wherein the active ingredient is a steroid, an anti-inflammatory compound, or an anti-angiogenesis compound.

24. A method for treating an ocular condition in patient, the method comprising implanting a drug delivery system into an ocular region of the patient, wherein the drug delivery system is a system according to claim 1.

2. A drug delivery system for treating an ocular condition which comprises a bioerodible implant comprising a plurality of rod-shaped segments, wherein:

a) each of the segments comprises (i) an active agent for treating the ocular condition and (ii) a bioerodible polymer;

b) at least some of the segments have drug release characteristics different from other that of other segments;

c) the segments are joined together at the ends thereof to form a contiguous rod-shaped implant; and

d) the segments are joined at the ends thereof in a manner to permit separation of the segments from each other in situ into individual segments following implantation into the ocular region of a patient.

3. A drug delivery system for treating an ocular condition which comprises a bioerodible implant comprising a plurality of rod-shaped segments, wherein:

a) each of the segments comprises (i) an active agent for treating the ocular condition and (ii) a bioerodible polymer;

b) at least some of the segments have drug release characteristics different from other of the segments; and

c) at least some of the segments having at least one end thereof having a cut surface that is at an angle to the longitudinal axis of less than 90°

or having at least one end which is of beveled shape.

4. A drug delivery system according to claim 3, wherein the individual segments are joined together at the ends thereof to form a contiguous rod-shaped implant having a longitudinal axis, the segments being joined together in a matrix comprised of a bioerodible polymer in a manner to permit separation of the segments from each other in situ into individual segments following implantation into the ocular region of a patient.

16. The drug delivery system according to claim 16, wherein the active ingredient is a member selected from the group consisting of methotrexate, etinoic acid, aspirin, diclofenac, flurbiprofen, ibuprofen, ketorolac, naproxen, uprofen, dexamethasone, cortisone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.

17. A method of manufacturing a drug delivery system which comprises a bioerodible implant, the method comprising:

a) blending a first active agent with a first bioerodible polymer to form a first active agent polymer mixture;

b) forming the first active agent polymer mixture into a rod shaped first implant segment having a longitudinal axis;

c) blending a second active agent with a second bioerodible polymer to form a second active agent polymer mixture;

d) forming at least some of the segments with at least one end thereof having a cut surface that is at an angle to the longitudinal axis of less than 90°

or has a beveled shape.

18. The method according to claim 17, further comprising joining the segments at the ends thereof to permit separation from each other in situ into individual segments following implantation into a patient.

19. The method according to claim 17, wherein each of the segments is formed with at least one end having a cut surface that is at an angle to the longitudinal axis of less than 90°

or one end having a beveled shaped surface.

20. The method according to 17, wherein the bioerodible polymer comprises at least one member selected from the group consisting of poly(lactide) polymers and poly(lactide-co-glycolide) copolymers.

21. The method according to claim 17, wherein at least one excipient that modifies the erosion characteristics of the bioerodible polymer is blended with the active agent and the bioerodible polymer.

22. The method according to claim 21, wherein the excipient is a member selected from the group consisting of long chain fatty alcohols, cholesterol, and high molecular weight polyethylene glycol polymers.

23. The method according to claim 17, wherein the bioerodible polymer comprises a poly(D,L-lactide-co-glycolide) copolymer with a monomer ratio in the range of 50:

50 to 85;

15.