Methods for manufacturing delivery devices and devices thereof
View Patent ↗Described herein are methods for reducing and achieving the desired release of an agent from a delivery system. The desired release kinetics are achieved by exposing the surface of the delivery system with a fluid for a desired period of time.
1. A method for preparing a device comprising an agent, comprising
(a) admixing at least one polymer and at least one agent to produce an admixture;
(b) processing the admixture to produce a device of a desired shape, wherein the device comprises at least two exposed surfaces; and
(c) contacting the device with a sufficient amount of a fluid for a sufficient time to change the surface morphology of the polymer; wherein the fluid diffuses into the outer layer of the polymer to gel the polymer thereby producing a smoother surface coating on the device, wherein at least one exposed surface or least one part of at least one exposed surface of the device is not contacted with the fluid;
wherein steps (a) and (b) do not involve the use of a solvent; and
wherein the fluid consists essentially of methylene chloride, chloroform, acetone, anisole, methyl acetate, ethyl acetate, N-methyl-2- pyrrolidone, hexafluoroisopropanol, tetrahydrofuran, dimethylsulfoxide, 2-pyrollidone, triethyl citrate, ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, Miglyol 810, isopropanol, ethanol, super critical carbon dioxide, or acetonitrile, or a mixture thereof.
2. The method of claim 1 , wherein at least two exposed surfaces of the device are not contacted with the fluid.
3. The method of claim 1 , wherein two exposed surfaces of the device are not contacted with the fluid.
4. The method of claim 1 , wherein the device comprises a rod, a fiber, a disc, a wafer, a bead, a ribbon, or a cylinder.
5. The method of claim 1 , wherein the device comprises a rod comprising two ends and a longitudinal surface, wherein the ends of the rod are not contacted with the fluid, and wherein the longitudinal surface is contacted with the fluid.
6. The method of claim 1 , wherein the device comprises a rod comprising two ends and a longitudinal surface, wherein after contacting the device with the fluid, at least one end of the rod is removed to expose an untreated end.
7. The method of claim 1 , wherein the processing step comprises melt extruding, injection molding, compression molding, or roller compacting the admixture into a desired shape.
8. The method of claim 1 , wherein the fluid consists essentially of ethyl acetate.
9. The method of claim 1 , wherein the agent comprises a bioactive agent.
10. The method of claim 9 , wherein the bioactive agent comprises a drug, an immunological agent, an antigen, a protein, a peptide, an oligonucleotide, or a mixture thereof.
11. The method of claim 1 , wherein the agent comprises an adhesive, a pesticide, a fragrance, an antifoulant, a dye, a salt, an oil, an ink, a cosmetic, a catalyst, a detergent, a curing agent, a flavor, a fuel, a herbicide, a metal, a paint, a photographic agent, a biocide, a pigment, a plasticizer, a propellant, a stabilizer, or a polymer additive, or any combination thereof.
12. The method of claim 1 , wherein the polymer comprises a biodegradable polymer, wherein the biodegradable polymer comprises a poly(lactide), a poly(glycolide), a poly(lactide-co-glycolide), a poly(lactic acid), a poly(glycolic acid), a poly(lactic acid-co-glycolic acid), a poly(caprolactone), or a poly(lactide-co-caprolactone), or a combination, blend, or copolymer thereof.
13. The method of claim 12 , wherein the biodegradable polymer comprises a polymer formed from components comprising 40 to 100 mole % lactide and from 0 to 60 mole % glycolide.
14. The method of claim 12 , wherein the biodegradable polymer comprises poly(lactide-co-glycolide), poly(lactide), poly(caprolactone), or a combination, blend, or copolymer thereof.
15. The method of claim 1 , wherein admixing step (a) comprises dry blending poly(lactide-co-glycolide), poly(lactide), or a combination, blend, or copolymer thereof, with a bioactive agent to produce an admixture, melt extruding the admixture to produce a rod, contacting the rod with ethyl acetate, and cutting the rod into one or more smaller rods having a predetermined length.
16. The method of claim 1 , wherein the device is not a sphere.
17. The method of claim 1 , wherein the device is not a microsphere or a microparticle.
18. The method of claim 1 , wherein the polymer comprises a polymer of ethylene-vinyl acetate.