Polymeric drug formulations

1. A method of forming a polymeric drug formulation comprising:

blending a water-soluble drug with a water-insoluble tissue-compatible polymer that is miscible in the solid phase with said drug and with a poly(alkylene oxide), in a solvent system capable of forming a homogeneous solution of said drug, said tissue-compatible polymer and said poly(alkylene oxide); and

adding said solution to an amount of a non-solvent for said drug, said tissue-compatible polymer and said poly(alkylene oxide), so that a microdomain-separated solid co-precipitate of said drug, said tissue-compatible polymer and said poly(alkylene oxide) is formed, wherein said poly(alkylene oxide) is blended in an amount effective to form phase-separated microdomains in said co-precipitate.

2. The method of claim 1 , wherein said tissue-compatible polymer is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and copolymers thereof, poly(ethylene-co-vinyl acetate), poly(caprolactone), poly(orthoesters), poly(carbonates), poly(arylates), poly(iminocarbonates), poly(vinyl pyrrolidone), pyran copolymer, poly(hydroxypropyl methacrylamide-phenol), poly(hydroxyethyl-aspartamide phenol), poly(ethylene oxide)-poly(lysine) substituted with palmitoyl residues, poly(hydroxybutyric acid), poly(acetals), poly(dihydro-pyran), poly(cyanoacrylates) and cross-linked and amphipathic block copolymers of hydrogels.

3. The method of claim 2 , wherein said tissue-compatible polymer is a poly(arylate).

4. The method of claim 3 , wherein said poly(arylate) is poly(desaminotyrosyl-tyrosine hexyl ester adipate).

5. The method of claim 1 , wherein said water-soluble drug is a non-peptide drug selected from the group consisting of natural and unnatural antibiotics, cytotoxic agents and oligonucleotides.

6. The method of claim 1 , wherein said water-soluble drug is a peptide drug selected from the group consisting of immunoglobulins, immunoglobulin fragments and platelet aggregation inhibiting peptides.

7. The method of claim 6 , wherein said peptide drug is a platelet aggregation inhibiting peptide.

8. The method of claim 1 , containing a drug loading up to about 50 percent by weight.

9. The method of claim 8 , containing a drug loading up to about 30 percent by weight.

10. The method of claim 9 , containing a drug loading between about 10 and about 20 percent by weight.

11. The method of claim 1 , wherein said poly(alkylene oxide) is poly(ethylene glycol).

12. The method of claim 1 , wherein said poly(alkylene oxide) is present at a level between about 2 and about 30 percent by weight.

13. The method of claim 1 , wherein said blending step comprises dissolving said water-soluble drug in a first solvent in which said drug is soluble, dissolving said tissue-compatible polymer in a second solvent in which said polymer is soluble, and dissolving said poly(alkylene oxide) in whichever of said first and second solvents said poly(alkylene oxide) is soluble; and combining said first and second solvent solutions, wherein said first solvent and said second solvent are capable of forming a homogeneous solution with each other, said drug, said tissue-compatible polymer and said poly(alkylene oxide).

14. The method of claim 1 , wherein said solvent system comprises at least one solvent selected from the group consisting of methanol, methylene chloride, ethanol, ethylene glycol, glycerol, tetrahydrofuran, ethyl acetate, acetonitrile, acetone, diisopropyl ether, methyl t-butyl ether, chloroform, carbon tetrachloride, dichloroethane and water.

15. The method of claim 1 , wherein said drug, said tissue-compatible polymer and said poly(alkylene oxide) are each dissolved in said solvent system at a level between about 1 and about 30 percent by weight.

16. The method of claim 1 , wherein said non-solvent is selected from the group consisting of diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl ethyl ketone, acetonitrile, toluene, xylene and carbon tetrachloride.

17. The method of claim 1 , wherein said solution of said drug, said tissue-compatible polymer and poly(alkylene oxide) is added to at least 5 to 10 volumes of said non-solvent compared to the volume of said solvent system.

18. A polymeric drug formulation prepared by the method of claim 1 .

19. The polymeric drug formulation of claim 18 , wherein said water-soluble drug is a platelet aggregation inhibiting peptide.

20. A method for site-specific drug delivery comprising implanting in the body of a patient in need thereof a polymeric drug formulation comprising a non-releasing single-phase dispersion of a water-soluble drug in a water-insoluble tissue-compatible polymer matrix, and a water-soluble poly(alkylene oxide) that is present in an amount effective to increase the release rate of said water-soluble drug from said tissue-compatible polymer matrix.

21. The method of claim 20 , wherein said water-soluble drug is a platelet aggregation inhibiting peptide.

22. The method of claim 21 , wherein said polymeric drug formulation is implanted during or following a cardiovascular procedure in which a stent is inserted into an artery, and said implanting step comprises the step of placing a film of said drug formulation between the wall of said artery and said stent, so that local release of said platelet aggregation inhibiting peptide reduces the formation of blood clots at said stent insertion site.

23. The method of claim 21 , wherein said polymeric drug formulation is implanted as a coating on the surface of a blood-contacting device or implant.