Processes for manufacturing polymeric microspheres
View Patent ↗Processes of manufacturing polymeric microspheres facilitate the generation of polymeric microspheres of size ranges smaller than 600 microns diameter by forming beads of a predetermined size from a starting material which may include a template polymer, and subsequently contacting the beads with a structural polymer. After crosslinking of the structural polymer has taken place, the template polymer may be removed to form the finished microspheres.
1. A method for producing spherical polymeric particles, the method comprising the steps of:
generating spherical beads of a desired size from a starting material comprising a template polymer;
diffusing a structural polymer into the beads; and
crosslinking the structural polymer, thereby producing polymeric spherical particles.
2. The method of claim 1 , wherein the generating step comprises use of a droplet generator.
3. The method of claim 1 , wherein the generating step comprises spheronization.
4. The method of claim 1 , wherein the beads are porous.
5. The method of claim 4 , wherein the beads comprise a template polymer selected from the group consisting of alginate, polysaccharide, carrageenan, chitosan, hyaluronic acid, and carboxylic-, sulfate-, or amine-functionalized polymers.
6. The method of claim 2 , wherein the generating step comprises (i) forming droplets by forcing a mixture comprising the template polymer and a solvent through the droplet generator, and (ii) depositing the droplets into a gelling solution comprising gelling ions to solidify the droplets into beads, the beads having a porosity gradient.
7. The method of claim 6 , wherein the solvent does not affect crosslinking of the structural polymer.
8. The method of claim 6 , wherein the gelling solution further comprises non-gelling ions to limit the porosity gradient.
9. The method of claim 6 , wherein the gelling solution does not contain non-gelling ions so as not to limit the porosity gradient.
10. The method of claim 1 , wherein diffusing comprises soaking the beads in a solution comprising the structural polymer.
11. The method of claim 1 , further comprising the step of removing the template polymer subsequent to the crosslinking step by subjecting the spherical polymeric particles to a solvent selective for the template polymer only.
12. The method of claim 11 , wherein the solvent comprises a solution of sodium hexametaphosphate.
13. The method of claim 11 , wherein the solvent comprises a solution of ethylene diamine tetraacetic acid.
14. The method of claim 11 , wherein the solvent comprises acetone.
15. The method of claim 1 , wherein the resulting polymeric spherical particles are in the range of 1-50 microns diameter.
16. The method of claim 1 , wherein the resulting polymeric spherical particles are in the range of 50-100 microns diameter.
17. The method of claim 1 , wherein the resulting polymeric spherical particles are in the range of 100-600 microns diameter.
18. The method of claim 1 , wherein the resulting polymeric spherical particles are in the range of 600-1000 microns diameter.
19. The method of claim 1 , wherein the template polymer is a shape-forming agent.
20. The method of claim 1 , wherein the structural polymer is selected from the group consisting of polyvinyl alcohol, polyacrylamide, polyethylene glycol, polyamides, polyureas, polyurethanes, and derivatives thereof.
21. The method of claim 1 , wherein the crosslinking step comprises application of a crosslinking agent.
22. The method of claim 21 , wherein the crosslinking agent forms covalent bonds with the structural polymer.
23. The method of claim 1 , wherein the crosslinking step comprises application of radiation.
24. The method of claim 21 , wherein the starting material comprises the crosslinking agent.
25. A method for producing spherical polymeric particles, the method comprising:
generating spherical beads of a desired size from a starting material comprising a methacrylate template polymer;
contacting the beads with a structural polymer; and
crosslinking the structural polymer, thereby producing spherical polymeric particles.
26. The method of claim 25 , wherein the beads further comprise a filler agent.
27. The method of claim 26 , wherein the filler agent is starch.
28. The method of claim 25 , wherein the beads are substantially non-porous.
29. A method for producing spherical polymeric particles comprising the steps of:
generating ice beads;
contacting the beads with a structural polymer; and
crosslinking the structural polymer, thereby producing polymeric spherical particles.
30. The method of claim 29 , further comprising the step of removing the ice subsequent to the crosslinking step by exposing the particles to an elevated temperature.
31. The method of claim 29 , wherein the contacting step comprises coating the beads with the structural polymer.
32. The method of claim 29 , wherein the structural polymer is selected from the group consisting of polyvinyl alcohol, polyacrylamide, polyethylene glycol, polyamides, polyureas, polyurethanes, and derivatives thereof.
33. A method, comprising:
contacting a template polymer with a structural polymer to form a particle comprising the template polymer and the structural polymer; and
removing at least a portion of the template polymer from the particle.
34. The method of claim 33 , further comprising, after contacting the template polymer and the structural polymer but before removing the portion of the template polymer, cross-linking the structural polymer.
35. The method of claim 34 , wherein cross-linking the structural polymer includes contacting the structural polymer with a cross-linking agent.
36. The method of claim 35 , wherein the cross-linking agent is selected from the group consisting of formaldehyde and glutaraldehyde.
37. The method of claim 33 , further comprising, before contacting the template polymer with the structural polymer, forming droplets of the template polymer.
38. The method of claim 37 , wherein forming the droplets of the template polymer includes passing a solution containing the template polymer through a nozzle.
39. The method of claim 38 , wherein passing the solution containing the template polymer through the nozzle forms a stream containing the template polymer.
40. The method of claim 39 , further comprising subjecting the nozzle to a periodic disturbance to break up the stream containing the template polymer.
41. The method of claim 33 , wherein the template polymer comprises a polysaccharide.
42. The method of claim 41 , wherein the polysaccharide comprises alginate.
43. The method of claim 33 , wherein the template polymer is selected from the group consisting of carrageenans, chitosan, hyaluronic acid, carboxylic-functionalized polymers, sulfate-functionalized polymers, amine-functionalized polymers, blends thereof, and derivatives thereof.
44. The method of claim 33 , wherein the structural polymer is selected from the group consisting of vinyl polymers, polyacrylamides, polyethylene glycols, polyamides, polyureas, polyurethanes, polyvinyl alcohols, and derivatives thereof.
45. The method of claim 44 , wherein the structural polymer comprises a polyvinyl alcohol.
46. The method of claim 33 , wherein the particle has a diameter of less than 600 microns.
47. The method of claim 46 , wherein the particle has a diameter of 1 to 50 microns.
48. The method of claim 46 , wherein the particle has a diameter of 50 to 100 microns.
49. The method of claim 46 , wherein the particle has a diameter of 100 to 600 microns.
50. The method of claim 33 , wherein the particle has a diameter of 600 to 1000 microns.
51. The method of claim 33 , wherein the template polymer comprises alginate, the structural polymer comprises a polyvinyl alcohol, and the particle has a diameter of less than 600 microns.
52. A method, comprising:
contacting a first polymer with a second polymer to form a particle comprising the first and second polymers; and
removing at least a portion of the first polymer from the particle,
wherein the particle has a diameter of about 1000 microns or less.
53. The method of claim 52 , wherein the first polymer comprises a polysaccharide.
54. The method of claim 53 , wherein the polysaccharide comprises alginate.
55. The method of claim 52 , wherein the first polymer is selected from the group consisting of carrageenans, chitosan, hyaluronic acid, carboxylic-functionalized polymers, sulfate-functionalized polymers, amine-functionalized polymers, blends thereof, and derivatives thereof.
56. The method of claim 52 , wherein the second polymer is selected from the group consisting of vinyl polymers, polyacrylamides, polyethylene glycols, polyamides, polyureas, polyurethanes, polyvinyl alcohols, and derivatives thereof.
57. The method of claim 52 , wherein the second polymer comprises a polyvinyl alcohol.