Apparatus and method for preparing microparticles
View Patent ↗Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.
1. A method for controlling particle size distribution of microparticles, comprising:
preparing a first phase, the first phase comprising an active agent and a polymer;
preparing a second phase;
preparing a quench liquid;
pumping the first phase and the second phase through a manifold that includes a plurality of static mixers to form an emulsion;
flowing the emulsion into the quench liquid whereby droplets of the emulsion form microparticles; and
adjusting a residence time of the emulsion in the manifold to obtain a predetermined particle size distribution of the resulting microparticles, wherein the residence time is equal to a length of the manifold divided by an average velocity of the emulsion through the manifold.
2. The method of claim 1 , wherein the adjusting step is carried out to increase the residence time, thereby narrowing particle size distribution.
3. The method of claim 1 , wherein the adjusting step is carried out to decrease the residence time, thereby broadening particle size distribution.
4. The method of claim 1 , wherein the manifold comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.
5. The method of claim 1 , wherein the adjusting step is carried out by changing the length of the manifold.
6. The method of claim 1 , wherein the adjusting step is carried out by changing the velocity of the emulsion in the manifold.
7. The method of claim 1 , wherein the residence time is from 3 to 4 seconds.
8. The method of claim 1 , wherein the residence time is less than one second.
9. The method of claim 1 , wherein the manifold comprises a scissors mixing element.
10. The method of claim 1 , wherein the manifold comprises a helical mixing element.
11. The method of claim 1 , wherein the manifold comprises a layered mixing element.
12. A method for controlling particle size distribution of microparticles, comprising:
combining a first phase and a second phase in a manifold to form an emulsion, wherein the manifold comprises a plurality of static mixers and the first phase comprises an active agent and a polymer;
flowing the emulsion into an extraction liquid for extracting the solvent from the emulsion to form microparticles; and
adjusting a residence time of the emulsion in the manifold to obtain a predetermined particle size distribution of the resulting microparticles, wherein the residence time is equal to a length of the manifold divided by an average velocity of the emulsion through the manifold.
13. The method of claim 12 , wherein the adjusting step is carried out to increase the residence time, thereby narrowing particle size distribution.
14. The method of claim 12 , wherein the adjusting step is carried out to decrease the residence time, thereby broadening particle size distribution.
15. The method of claim 12 , wherein the manifold comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.
16. The method of claim 12 , wherein the adjusting step is carried out by changing the length of the manifold.
17. The method of claim 12 , wherein the adjusting step is carried out by changing the velocity of the emulsion in the manifold.
18. The method of claim 12 , wherein the residence time is from 3 to 4 seconds.
19. The method of claim 12 , wherein the residence time is less than one second.
20. The method of claim 12 , wherein the manifold comprises a scissors mixing element.
21. The method of claim 12 , wherein the manifold comprises a helical mixing element.
22. The method of claim 12 , wherein the manifold comprises a layered mixing element.
23. A method for controlling particle size distribution of microparticles, comprising:
combining a first phase and a second phase in a static mixing assembly to form an emulsion, wherein the first phase comprises an active agent, a polymer, and a solvent;
flowing the emulsion into an extraction liquid for extracting the solvent from the emulsion to form microparticles; and
adjusting a velocity of the emulsion through the static mixing assembly to obtain a predetermined droplet size, wherein an average velocity of the emulsion is equal to a length of the static mixing assembly divided by the residence time of the emulsion in the static mixing assembly.
24. The method of claim 23 , wherein the adjusting step is carried out to increase the droplet size, thereby broadening particle size distribution.
25. The method of claim 23 , wherein the adjusting step is carried out to decrease the droplet size, thereby narrowing particle size distribution.
26. The method of claim 23 , wherein the static mixing assembly comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.
27. The method of claim 23 , wherein the adjusting step is carried out by changing the length of the static mixing assembly.
28. The method of claim 23 , wherein the static mixing assembly comprises a scissors mixing element.
29. The method of claim 23 , wherein the static mixing assembly comprises a helical mixing element.
30. The method of claim 23 , wherein the static mixing assembly comprises a layered mixing element.