Bioerodible sustained release drug delivery systems

1. A drug delivery system comprising:

an inner core, comprising (i) a biocompatible fluid component consisting of polyethylene glycol, (ii) a biocompatible solid component dispersed, suspended, or dissolved in the biocompatible fluid component, wherein the biocompatible solid component is poly(dl-lactide-co-glycolide) and is more soluble in the biocompatible fluid component than in physiological fluid, and (iii) at least one agent dispersed, suspended, or dissolved within the inner core, wherein the inner core undergoes a phase change upon contact with a physiological fluid;

a first polymer layer, impermeable to the passage of the at least one agent, that covers at least part of but less than 100% of said inner core; and optionally, a second polymer layer that is permeable to the passage of the at least one agent; wherein the release rate of the agent is limited primarily by the portion of the inner core that is covered by the first polymer layer, the physical properties of the core, the dissolution rate of the core or components of the core, the permeability of the second polymer layer, or the solubility of the at least one agent in the physiological fluid immediately surrounding the polymer.

2. The drug delivery system of claim 1 , wherein the first polymer layer covers at least about 50% of the inner core.

3. The drug delivery system of claim 1 , wherein the inner core forms a gel upon contact with physiological fluid.

4. The drug delivery system of claim 3 , wherein the at least one agent is at least 10% more soluble in the inner core in gel form than in the inner core prior to conversion to said gel.

5. The drug delivery system of claim 1 , wherein, after contact with physiological fluid, the inner core is at least 10% less permeable to the agent than is the inner core prior to interaction with said fluid.

6. The drug delivery system of claim 1 , wherein the at least one agent has a permeability coefficient in the second layer at least about 1×10 −5 cm/s but less than about 1×10 −2 cm/s.

7. The drug delivery system of claim 1 , wherein the at least one agent has a release rate from the drug delivery system that is limited primarily by the permeability of the at least one agent in the inner core.

8. The drug delivery system according to claim 1 , wherein the device is water-permeable.

9. The drug delivery system according to claim 1 , wherein the inner core comprises a codrug or prodrug that is cleaved by water that permeates into the inner core.

10. The drug delivery device according to claim 1 , wherein the at least one agent is a prodrug.

11. The drug delivery system of claim 10 , wherein the at least one agent is covalently linked to a polyoxyethylene ether.

12. A drug delivery device, comprising:

the drug delivery system according to claim 1 ; and

a pharmaceutically acceptable carrier capable of delivering the at least one agent to a site within the body.

13. The drug delivery device of claim 12 , wherein the at least one agent is a prodrug comprising an agent covalently linked to a polyoxyethylene ether.

14. A method of administering an agent to a patient in need thereof, comprising:

providing the drug delivery system according to claim 1 , said system containing an effective amount of an agent suitable for treating the patient; and

administering the drug delivery system to the patient.

15. A method of manufacturing a drug delivery system, comprising: providing an inner core, said inner core comprising (i) a biocompatible solid component, (ii) a biocompatible fluid component consisting of polyethylene glycol, wherein the biocompatible solid is poly(dl-lactide-co-glycolide) and is more soluble in the biocompatible fluid than in physiological fluid, and (iii) at least one agent dispersed within said inner core; wherein the inner core undergoes a phase change upon contact with a physiological fluid; and combining said inner core with a first polymer layer that is impermeable to the at least one agent and covers at least part of but less than 100% of said inner core; and optionally, adding a second polymer layer that is permeable to the passage of the at least one agent; wherein the release rate of the agent is limited primarily by the portion of the inner core that is covered by the first polymer layer, the physical properties of the core, the dissolution rate of the core or components of the core, the permeability of the second polymer layer, or the solubility of the at least one agent in the physiological fluid immediately surrounding the polymer.

16. The method of claim 15 , wherein the inner core and first polymer layer are combined by co-extrusion.

17. A medical device, comprising the drug delivery system according to claim 1 adapted to provide a drug to a patient in need thereof.

18. A drug delivery system of claim 1 , wherein the first polymer layer is a formed of a material selected from polyvinyl acetate, cross-linked polyvinyl alcohol, cross-linked polyvinyl butyrate, ethylene ethylacrylate copolymer, polyethyl hexylacrylate, polyvinyl chloride, polyvinyl acetals, plasticized ethylene vinylacetate copolymer, polyvinyl alcohol, ethylene vinylchloride copolymer, polyvinyl esters, polyvinylbutyrate, polyvinylformal, polyamides, polymethylmethacrylate, polybutylmethacrylate, plasticized polyvinyl chloride, plasticized nylon, plasticized soft nylon, plasticized polyethylene terephthalate, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, polytetrafluoroethylene, polyvinylidene chloride, polyacrylonitrile, cross-linked polyvinylpyrrolidone, polytrifluorochloroethylene chlorinated polyethylene, poly(1,4-isopropylidene diphenylene carbonate), vinylidene chloride, acrylonitrile copolymer, vinyl-chloride-diethyl fumarate copolymer, silicone rubbers, medical grade polydimethylsiloxanes, ethylene-propylene rubber, silicone-carbonate copolymers, vinylidene chloride-vinyl chloride copolymer, vinyl chloride-acrylonitrile copolymer, and vinylidene chloride-acrylonitride copolymer.

19. A drug delivery system of claim 18 , wherein the first polymer layer is formed of a material selected from cross-linked polyvinyl alcohol, plasticized ethylene vinylacetate copolymer, polyvinyl alcohol, polymethylmethacrylate, plasticized nylon, plasticized soft nylon, silicone rubbers, and silicone-carbonate copolymers.

20. A method of claim 15 , wherein the first polymer layer is formed of a material selected from polyvinyl acetate, cross-linked polyvinyl alcohol, cross-linked polyvinyl butyrate, ethylene ethylacrylate copolymer, polyethyl hexylacrylate, polyvinyl chloride, polyvinyl acetals, plasticized ethylene vinylacetate copolymer, polyvinyl alcohol, ethylene vinylchloride copolymer, polyvinyl esters, polyvinylbutyrate, polyvinylformal, polyamides, polymethylmethacrylate, polybutylmethacrylate, plasticized polyvinyl chloride, plasticized nylon, plasticized soft nylon, plasticized polyethylene terephthalate, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, polytetrafluoroethylene, polyvinylidene chloride, polyacrylonitrile, cross-linked polyvinylpyrrolidone, polytrifluorochloroethylene chlorinated polyethylene, poly(1,4-isopropylidene diphenylene carbonate), vinylidene chloride, acrylonitrile copolymer, vinyl-chloride-diethyl fumarate copolymer, silicone rubbers, medical grade polydimethylsiloxanes, ethylene-propylene rubber, silicone-carbonate copolymers, vinylidene chloride-vinyl chloride copolymer, vinyl chloride-acrylonitrile copolymer, and vinylidene chloride-acrylonitride copolymer.

21. A method of claim 20 , wherein the first polymer layer is formed of a material selected from cross-linked polyvinyl alcohol, plasticized ethylene vinylacetate copolymer, polyvinyl alcohol, polymethylmethacrylate, plasticized nylon, plasticized soft nylon, silicone rubbers, and silicone-carbonate copolymers.

22. The drug delivery system of claim 1 , wherein the at least one agent is a peptide or protein.

23. The method of claim 15 , wherein the at least one agent is a peptide or protein.