Biodegradable vehicles and delivery systems of biolgically active substances

• US 20040018238A1
• Filed: 04/11/2003
• Published: 01/29/2004
• Est. Priority Date: 02/26/2001
• Status: Abandoned Application

• Current Assignee: Atul J. Shukla
• Original Assignee: Atul J. Shukla
• Inventors: Shukla, Atul J
• Application Number:
  US10/312,394
• Publication Number:
  US 20040018238A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00

Abstract

Biodegradable vehicle and delivery systems of physiologically, pharmacologically and biologically active substance(s) (BAS) are provided. The biodegradable vehicles may be prepared by blending biodegradable polymers and plasticizers using a novel solvent evaporation method. This method involves dissolving the biodegradable polymer or copolymer and a plasticizer or mixtures of plasticizers into a volatile solvent or mixtures of volatile solvents. The volatile solvent is then removed using vacuum or at an elevated temperature or using a combination of both vacuum and elevated temperature. The biodegradable vehicle can be used as filler or spacer in the body. Biologically active substances (BAS) can be added to the biodegradable vehicle at any step during or after preparing the biodegradable vehicle, or just prior to using the biodegradable system. This biodegradable delivery system provides controlled release of the BAS over the desired period of time. The biodegradable vehicle or BAS-loaded biodegradable delivery system can be injected, implanted, smeared or applied in vivo in an animal, bird or human.

Claims

1. A biodegradable vehicle or delivery system comprising:

(a) at least one biodegradable polymer; and

(b) at least one plasticizer;

said plasticizer being capable of modulating both the consistency and hydrophobicity or hydrophilicity of said biodegradable vehicle or delivery system.

2. The biodegradable delivery system of claim 1 further comprising at least one biologically active substance.

3. The biodegradable vehicle and delivery system of claim 1 wherein said biodegradable polymer is selected from a group consisting of homopolymers and copolymers or blends thereof, of polyesters, polyphosphoesters, polyorthoesters, polylactic acid or polylactides, polyglycolic acid or polyglycolides, polycaprolactones, polyalkylcyanoacrylates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyaminoacids, pseudopolyamino acids, polyamides, polyanhydrides, polydioxanone, poly(ε

-decaloactone), poly(glycolide-co-trimethylene carbonate), poly(ethylene carbonate), poly(iminocarbonate), poly(1,3-propylene malonate), poly(ethylene-1,4-phenylene-bis-oxyacetate), and poly(ester-amides).

4. The biodegradable vehicle and delivery system of claim 1 wherein said plasticizer is selected from a group consisting of citrates such as diethyl citrate (DEC), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), butyryltri-n-hexyl-citrate, acetyltri-n-hexyl citrate, phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate, glycol ethers such as ethylene glycol diethyl ether, propylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether (Transcutol®

), propylene glycol monotertiary butyl ether, dipropylene glycol monomethyl ether, N-methyl-2-pyrrolidone, 2 pyrrolidone (2-Pyrrol®

), isopropyl myristate, isopropyl palmitate, dimethylacetamide, propylene glycol, glycerol, glyceryl dioleate, ethyl oleate, benzylbenzoate, glycofurol, sorbitol, sucrose acetate isobutyrate, sebacates such as dibutyl sebacate, dipropylene glycol methyl ether acetate (DPM acetate), propylene carbonate, propylene glycol laurate, propylene glycol caprylate/caprate, gamma butyrolactone, polyethylene glycols (PEG), vegetable oils obtained from seeds, flowers, fruits, leaves, stem or any part of a plant or tree such as cotton seed oil, soy bean oil, almond oil, sunflower oil, peanut oil, sesame oil, glycerol and PEG esters of acids and fatty acids (Gelucires®

, Labrafils® and

Labrasol®

) such as PEG-6 glycerol mono oleate, PEG-6 glycerol linoleate, PEG-8 glycerol linoleate, PEG-4 glyceryl caprylate/caprate, PEG-8 glyceryl caprylate/caprate, polyglyceryl-3-oleate, polyglyceryl-6-dioleate, polyglyceryl-3-isostearate, PEG-32 glyceryl laurate (Gelucire 44/1®

), PEG-32 glyceryl palmitostearate (Gelucire 50/13®

), PEG-32 glyceryl stearate (Gelucire 53/10®

), glyceryl behenate, cetyl palmitate, glyceryl di and tri stearate, glyceryl palmitostearate, and glyceryl triacetate (Triacetin®

).

5. The biodegradable delivery system of claim 2 wherein said biologically active substance is selected from the group consisting of steroids, hormones, antipsychotic agents, agents that act on the central nervous system (CNS-agents), narcotic agonists and antagonists, fertility regulating agents, antibodies and antigens, anesthetics, analgesics, antibiotics, antiviral agents, antineoplastic agents, antifungal agents, cavity and infection preventing agents, cardiovascular agents, angiogenic and antiangiogenic agents, anti-inflammatory agents, vasodilators, brochiodilators, alkaloids, peptides and proteins, vaccines, live or killed bacteria and viruses, agents or extracts derived from whole or parts of plants, trees, flowers, fruits, buds, seeds, leaves, barks, stem, roots, and animal tissues, growth promoting agents, soft and hard tissues, growth promoting agents, cells, tissues such as bones or agents derived there from, bone growth promoting agents such as calcium phosphates, calcium sulfate and hydroxyapatites, whole viable cells and cell-lines, deoxyribonucleic acid (DNA), DNA fragments, ribonucleic acid (RNA) RNA fragments, and biological tissues such as islets of langerhans and pancreas. The biologically active substance can be in the form of a solid, or dissolved or suspended in a in a plasticizer or mixtures of plasticizers.

6. A biodegradable vehicle or delivery system comprising:

(a) a combination of two biodegradable polymers, said polymers capable of modulating the degradation kinetics as well as consistency and hydrophobicity or hydrophilicity of the vehicle or delivery system; and

at least one plasticizer, said plasticizer being capable of modulating the consistency and hydrophobicity or hydrophilicity of said biodegradable vehicle or delivery system.

7. A biodegradable vehicle or delivery system comprising:

(a) a combination of three biodegradable polymers, said polymers capable of modulating the degradation kinetics as well as consistency and hydrophobicity or hydrophilicity of the vehicle or delivery system; and

(b) at least one plasticizer, said plasticizer being capable of modulating the consistency and hydrophobicity or hydrophilicity of said biodegradable vehicle or delivery system.

8. (e) A biodegradable vehicle or delivery system comprising:

(a) a combination of two biodegradable polymers, said polymers capable of modulating the degradation kinetics as well as consistency and hydrophobicity or hydrophilicity of the vehicle or delivery system; and

(b) a combination of two plasticizers, said plasticizers being capable of modulating the consistency and hydrophilicity or hydrophobicity of said biodegradable vehicle or delivery system.

9. A biodegradable vehicle or delivery system comprising:

(a) a combination of three biodegradable polymers, said polymers capable of modulating the degradation kinetics as well as consistency and hydrophobicity or hydrophilicity of the vehicle or delivery system; and

(b) a combination of two plasticizers, said plasticizers being capable of modulating the consistency and hydrophilicity or hydrophobicity of said biodegradable vehicle or delivery system.

10. A biodegradable vehicle or delivery system comprising:

(a) at least one biodegradable polymer; and

a combination of two plasticizers, said plasticizers being capable of modulating the consistency and hydrophilicity or hydrophobicity of said biodegradable vehicle or delivery system.

11. A method of preparing a biodegradable vehicle or delivery system comprising the steps of:

(a) selecting at least one biodegradable polymer;

(b) dissolving said polymer in at least one volatile solvent to form a solution;

(c) adding at least one plasticizer to said solution of step (b); and

(d) evaporating said solvent from the solution of step (c).

12. The method of claim 11 wherein said biodegradable polymer is selected from a group consisting homopolymers and copolymers or blends thereof, of polyesters, polyphosphoesters, polyorthoesters, polylactic acid or polylactides, polyglycolic acid or polyglycolides, polycaprolactones, polyalkylcyanoacrylates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyaminoacids, pseudopolyamino acids, polyamides, polyanhydrides, polydioxanone, poly(ε

-decaloactone), poly(glycolide-co-trimethylene carbonate), poly(ethylene carbonate), poly(iminocarbonate), poly(1,3-propylene malonate), poly(ethylene-1,4-phenylene-bis-oxyacetate), and poly(ester-amides).

13. The method of claim 11 wherein said volatile solvent is selected from a group consisting of acetone, methyl acetate, ethyl acetate, chloroform, dichloromethane, methyl ethyl ketone, hexafluroisopropanol, tetrahydrofuran and hexafluroacetone sesquihydrate.

14. The method in claim 11 wherein said plasticizer is selected from a group consisting of citrates such as diethyl citrate (DEC), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), butyryltri-n-hexyl-citrate, acetyltri-n-hexyl citrate, phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate, glycol ethers such as ethylene glycol diethyl ether, propylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol mono ethyl ether (Transcutol®

), propylene glycol monotertiary butyl ether, dipropylene glycol monomethyl ether, N-methyl-2-pyrrolidone, 2 pyrrolidone (2-Pyrrol®

), isopropyl myristate, isopropyl palmitate, dimethylacetamide, propylene glycol, glycerol, glyceryl dioleate, ethyl oleate, benzylbenzoate, glycofurol, sorbitol, sucrose acetate isobutyrate, sebacates such as dibutyl sebacate, dipropylene glycol methyl ether acetate (DPM acetate), propylene carbonate, propylene glycol laurate, propylene glycol caprylate/caprate, gamma butyrolactone, polyethylene glycols (PEG), vegetable oils obtained from seeds, flowers, fruits, leaves, stem or any part of a plant or tree such as cotton seed oil, soy bean oil, almond oil, sunflower oil, peanut oil, sesame oil, glycerol and PEG esters of acids and fatty acids (Gelucires®

, Labrafils® and

Labrasol®

) such as PEG-6 glycerol mono oleate, PEG-6 glycerol linoleate, PEG-8 glycerol linoleate, PEG-4 glyceryl caprylate/caprate, PEG-8 glyceryl caprylate/caprate, polyglyceryl-3-oleate, polyglyceryl-6-dioleate, polyglyceryl-3-isostearate, PEG-32 glyceryl laurate (Gelucire 44/1®

), PEG-32 glyceryl palmitostearate (Gelucire 50/13®

), PEG-32 glyceryl stearate (Gelucire 53/10®

), glyceryl behenate, cetyl palmitate, glyceryl di and tri stearate, glyceryl palmitostearate, and glyceryl triacetate (Triacetin®

).

15. The method in claim 11 further comprising the step of:

(e) adding at least one biologically active substance to the product of step (d) wherein the said biodegradable vehicle is loaded with at least one biologically active substance soon after preparing the biodegradable vehicle or just prior to using the biodegradable delivery system loaded with the biologically active substance.

16. The method in claim 15 wherein said biodegradable polymer is selected from a group consisting homopolymers and copolymers or blends thereof, of polyesters, polyphosphoesters, polyorthoesters, polylactic acid or polylactides, polyglycolic acid or polyglycolides, polycaprolactones, polyalkylcyanoacrylates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyaminoacids, pseudopolyamino acids, polyamides, polyanhydrides, polydioxanone, poly(ε

-decaloactone), poly(glycolide-co-trimethylene carbonate), poly(ethylene carbonate), poly(iminocarbonate), poly(1,3-propylene malonate), poly(ethylene-1,4-phenylene-bis-oxyacetate), and poly(ester-amides).

17. The method of claim 15 wherein said volatile solvent is selected from a group consisting of acetone, methyl acetate, ethyl acetate, chloroform, dichloromethane, methyl ethyl ketone, hexafluroisopropanol, tetrahydrofuran and hexafluroacetone sesquihydrate.

18. The method of claim 15 wherein said plasticizer is selected from a group consisting of citrates such as diethyl citrate (DEC), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), butyryltri-n-hexyl-citrate, acetyltri-n-hexyl citrate, phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate, glycol ethers such as ethylene glycol diethyl ether, propylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol mono ethyl ether (Transcutol®

), propylene glycol monotertiary butyl ether, dipropylene glycol monomethyl ether, N-methyl-2-pyrrolidone, 2 pyrrolidone (2-Pyrrol®

), isopropyl myristate, isopropyl palmitate, dimethylacetamide, propylene glycol, glycerol, glyceryl dioleate, ethyl oleate, benzylbenzoate, glycofurol, sorbitol, sucrose acetate isobutyrate, sebacates such as dibutyl sebacate, dipropylene glycol methyl ether acetate (DPM acetate), propylene carbonate, propylene glycol laurate, propylene glycol caprylate/caprate, gamma butyrolactone, polyethylene glycols (PEG), vegetable oils obtained from seeds, flowers, fruits, leaves, stem or any part of a plant or tree such as cotton seed oil, soy bean oil, almond oil, sunflower oil, peanut oil, sesame oil, glycerol and PEG esters of acids and fatty acids (Gelucires®

, Labrafils® and

Labrasol®

) such as PEG-6 glycerol mono oleate, PEG-6 glycerol linoleate, PEG-8 glycerol linoleate, PEG-4 glyceryl caprylate/caprate, PEG-8 glyceryl caprylate/caprate, polyglyceryl-3-oleate, polyglyceryl-6-dioleate, polyglyceryl-3-isostearate, PEG-32 glyceryl laurate (Gelucire 44/1®

), PEG-32 glyceryl palmitostearate (Gelucire 50/13®

), PEG-32 glyceryl stearate (Gelucire 53/10®

), glyceryl behenate, cetyl palmitate, glyceryl di and tri stearate, glyceryl palmitostearate, and glyceryl triacetate (Triacetin®

).

19. The method of claim 15 wherein said biologically active substance is selected from the group consisting of steroids, hormones, antipsychotic agents, agents that act on the central nervous system (CNS-agents), narcotic agonists and antagonists, fertility regulating agents, antibodies and antigens, anesthetics, analgesics, antibiotics, antiviral agents, antineoplastic agents, antifungal agents, cavity and infection preventing agents, cardiovascular agents, angiogenic and antiangiogenic agents, anti-inflammatory agents, vasodilators, brochiodilators, alkaloids, peptides and proteins, vaccines, live or killed bacteria and viruses, agents or extracts derived from whole or parts of plants, trees, flowers, fruits, buds, seeds, leaves, barks, stem, roots, and animal tissues, growth promoting agents, soft and hard tissues, growth promoting agents, cells, tissues such as bones or agents derived there from, bone growth promoting agents such as calcium phosphates, calcium sulfate and hydroxyapatites, whole viable cells and cell-lines, deoxyribonucleic acid (DNA), DNA fragments, ribonucleic acid (RNA) RNA fragments, and biological tissues such as islets of langerhans and pancreas. The biologically active substance can be in the form of a solid, or dissolved or suspended in a in a plasticizer or mixtures of plasticizers.

20. A method of preparing a biodegradable vehicle or delivery system comprising the steps of:

(a) selecting at least one biodegradable polymer (b) dissolving said polymer in at least one volatile solvent to form a solution;

(c) adding at least one plasticizer to said solution of step (b);

(d) adding at least one biologically active substance to the product of step (c); and

(e) evaporating said solvent from the product of step (d).

21. The method of claim 20 wherein said biodegradable polymer is selected from a group consisting homopolymers and copolymers or blends thereof, of polyesters, polyphosphoesters, polyorthoesters, polylactic acid or polylactides, polyglycolic acid or polyglycolides, polycaprolactones, polyalkylcyanoacrylates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyaminoacids, pseudopolyamino acids, polyamides, polyanhydrides, polydioxanone, poly(ε

-decaloactone), poly(glycolide-co-trimethylene carbonate), poly(ethylene carbonate), poly(iminocarbonate), poly(1,3-propylene malonate), poly(ethylene-1,4-phenylene-bis-oxyacetate), and poly(ester-amides).

22. The method of claim 20 wherein said volatile solvent is selected from a group consisting of acetone, methyl acetate, ethyl acetate, chloroform, dichloromethane, methyl ethyl ketone, hexafluroisopropanol, tetrahydrofuran and hexafluroacetone sesquihydrate.

23. The method of claim 20 wherein said plasticizer is selected from a group consisting of citrates such as diethyl citrate (DEC), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), butyryltri-n-hexyl-citrate, acetyltri-n-hexyl citrate, phthalates such as dimethyl phthalate (IMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate, glycol ethers such as ethylene glycol diethyl ether, propylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether (Transcutol®

), propylene glycol monotertiary butyl ether, dipropylene glycol monomethyl ether, N-methyl-2-pyrrolidone, 2 pyrrolidone (2-Pyrrol®

), isopropyl myristate, isopropyl palmitate, dimethylacetamide, propylene glycol, glycerol, glyceryl dioleate, ethyl oleate, benzylbenzoate, glycofurol, sorbitol, sucrose acetate isobutyrate, sebacates such as dibutyl sebacate, dipropylene glycol methyl ether acetate (DPM acetate), propylene carbonate, propylene glycol laurate, propylene glycol caprylate/caprate, gamma butyrolactone, polyethylene glycols (PEG), vegetable oils obtained from seeds, flowers, fruits, leaves, stem or any part of a plant or tree such as cotton seed oil, soy bean oil, almond oil, sunflower oil, peanut oil, sesame oil, glycerol and PEG esters of acids and fatty acids (Gelucires®

, Labrafils® and

Labrasol®

) such as PEG-6 glycerol mono oleate, PEG-6 glycerol linoleate, PEG-8 glycerol linoleate, PEG-4 glyceryl caprylate/caprate, PEG-8 glyceryl caprylate/caprate, polyglyceryl-3-oleate, polyglyceryl-6-dioleate, polyglyceryl-3-isostearate, PEG-32 glyceryl laurate (Gelucire 44/1®

), PEG-32 glyceryl palmitostearate (Gelucire 50/13®

), PEG-32 glyceryl stearate (Gelucire 53/10®

), glyceryl behenate, cetyl palmitate, glyceryl di and tri stearate, glyceryl palmitostearate, and glyceryl triacetate (Triacetin®

).

24. The method of claim 20 wherein said biologically active substance is selected from the group consisting of steroids, hormones, antipsychotic agents, agents that act on the central nervous system (CNS-agents), narcotic agonists and antagonists, fertility regulating agents, antibodies and antigens, anesthetics, analgesics, antibiotics, antiviral agents, antineoplastic agents, antifungal agents, cavity and infection preventing agents, cardiovascular agents, angiogenic and antiangiogenic agents, anti-inflammatory agents, vasodilators, brochiodilators, alkaloids, peptides and proteins, vaccines, live or killed bacteria and viruses, agents or extracts derived from whole or parts of plants, trees, flowers, fruits, buds, seeds, leaves, barks, stem, roots, and animal tissues, growth promoting agents, soft and hard tissues, growth promoting agents, cells, tissues such as bones or agents derived there from, bone growth promoting agents such as calcium phosphates, calcium sulfate and hydroxyapatites, whole viable cells and cell-lines, deoxyribonucleic acid (DNA), DNA fragments, ribonucleic acid (RNA) RNA fragments, and biological tissues such as islets of langerhans and pancreas.

25. A method for modulating the release kinetics of a biologically active substance (BAS) in a biodegradable delivery system comprising a biodegradable polymer, a plasticizer and a BAS, said method comprising:

varying the physiochemical properties of at least one member of the group consisting of said biodegradable polymer, said plasticizer, BAS and combinations thereof, thereby modulating the release kinetics of said biologically active substance (BAS).

26. The method of claim 25, wherein said biologically active substance is selected from the group consisting of steroids, hormones, antipsychotic agents, agents that act on the central nervous system (CNS-agents), narcotic agonists and antagonists, fertility regulating agents, antibodies and antigens, anesthetics, analgesics, antibiotics, antiviral agents, antineoplastic agents, antifungal agents, cavity and infection preventing agents, cardiovascular agents, angiogenic and antiangiogenic agents, anti-inflammatory agents, vasodilators, brochiodilators, alkaloids, peptides and proteins, vaccines, live or killed bacteria and viruses, agents or extracts derived from whole or parts of plants, trees, flowers, fruits, buds, seeds, leaves, barks, stem, roots, and animal tissues, growth promoting agents, soft and hard tissues, growth promoting agents, cells, tissues such as bones or agents derived there from, bone growth promoting agents such as calcium phosphates, calcium sulfate and hydroxyapatites, whole viable cells and cell-lines, deoxyribonucleic acid (DNA), DNA fragments, ribonucleic acid (RNA) RNA fragments, and biological tissues such as islets of langerhans and pancreas.

27. The method of claim 25 wherein said plasticizer is selected from a group consisting of citrates such as diethyl citrate (DEC), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), butyryltri-n-hexyl-citrate, acetyltri-n-hexyl citrate, phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate, glycol ethers such as ethylene glycol diethyl ether, propylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether (Transcutol®

), propylene glycol monotertiary butyl ether, dipropylene glycol monomethyl ether, N-methyl-2-pyrrolidone, 2 pyrrolidone (2-Pyrrol®

), isopropyl myristate, isopropyl palmitate, dimethylacetamide, propylene glycol, glycerol, glyceryl dioleate, ethyl oleate, benzylbenzoate, glycofurol, sorbitol, sucrose acetate isobutyrate, sebacates such as dibutyl sebacate, dipropylene glycol methyl ether acetate (DPM acetate), propylene carbonate, propylene glycol laurate, propylene glycol caprylate/caprate, gamma butyrolactone, polyethylene glycols (PEG), vegetable oils obtained from seeds, flowers, fruits, leaves, stem or any part of a plant or tree such as cotton seed oil, soy bean oil, almond oil, sunflower oil, peanut oil, sesame oil, glycerol and PEG esters of acids and fatty acids (Gelucires®

, Labrafils® and

Labrasol®

) such as PEG-6 glycerol mono oleate, PEG-6 glycerol linoleate, PEG-8 glycerol linoleate, PEG-4 glyceryl caprylate/caprate, PEG-8 glyceryl caprylate/caprate, polyglyceryl-3-oleate, polyglyceryl-6-dioleate, polyglyceryl-3-isostearate, PEG-32 glyceryl laurate (Gelucire 44/1®

), PEG-32 glyceryl palmitostearate (Gelucire 50/13®

), PEG-32 glyceryl stearate (Gelucire 53/10®

), glyceryl behenate, cetyl palmitate, glyceryl di and tri stearate, glyceryl palmitostearate, and glyceryl triacetate (Triacetin®

).

28. The method of claim 25 wherein said biodegradable polymer is selected from a group consisting homopolymers and copolymers or blends thereof, of polyesters, polyphosphoesters, polyorthoesters, polylactic acid or polylactides, polyglycolic acid or polyglycolides, polycaprolactones, polyalkylcyanoacrylates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyaminoacids, pseudopolyamino acids, polyamides, polyanhydrides, polydioxanone, poly(ε

-decaloactone), poly(glycolide-co-trimethylene carbonate), poly(ethylene carbonate), poly(iminocarbonate), poly(1,3-propylene malonate), poly(ethylene-1,4-phenylene-bis-oxyacetate), and poly(ester-amides).

29. A method for modulating the degradation kinetics of a biodegradable delivery vehicle comprising a biodegradable polymer, a plasticizer and optionally a biologically active substance said method comprising:

varying the physiochemical properties of at least one member of the group consisting of said biodegradable polymer, said plasticizer, optionally a BAS and combinations thereof, thereby modulating the degradation kinetics of said biodegradable vehicle.