Emulsion-based process for preparing microparticles and workhead assembly for use with same
View Patent ↗The present invention relates to emulsion and double-emulsion based processes for preparing microparticles. The invention also relates to workhead assemblies for in-line flow-through mixing devices that can be used for mixing two or more fluids. The workhead assemblies can be used with the processes for preparing microparticles.
1. A process for making microparticles, comprising:
(a) providing a process stream comprising (i) a dispersed phase comprising a first solvent having a polymer and an agent dissolved or dispersed therein; and (ii) a continuous phase comprising a second solvent that is partially or totally immiscible in the first solvent;
(b) passing the process stream through a screen and into a mixing environment, without a subsequent screen or perforated stator in the mixing environment; such that during step (a) and/or (b), an emulsion forms that comprises microdroplets of the dispersed phase in the continuous phase;
(c) at least substantially removing the first solvent from the microdroplets to form the microparticles; and wherein the process is performed without high-shear mixing, wherein the process stream is not subsequently screened in the mixing environment.
2. The process of claim 1 , wherein the first solvent is an organic solvent.
3. The process of claim 1 , wherein the second solvent is an aqueous solvent.
4. The process of claim 1 , wherein the continuous phase further comprises a surfactant.
5. The process of claim 1 , wherein the polymer is a biodegradable or biocompatible polymer.
6. The process of claim 1 , wherein the polymer comprises poly(lactide), poly(glycolide), poly(caprolactone), or a copolymer or mixture thereof.
7. The process of claim 1 , wherein the agent is a bioactive agent.
8. The process of claim 1 , wherein the solvent removal step is performed by freeze-drying or cryogenic extraction.
9. A process for making microparticles, comprising:
(a) providing a process stream comprising: a primary emulsion comprising microdroplets of (i) a first dispersed phase comprising a first solvent having an agent dissolved or dispersed therein, and (ii) a second dispersed phase comprising a second solvent that is partially or totally immiscible in the first solvent and having a polymer dissolved or dispersed therein; and a continuous phase comprising a third solvent that is partially or totally immiscible in the second solvent;
(b) passing the process stream through a screen and into a mixing environment; such that during steps (a) or (b), a double-emulsion forms comprising the first and second dispersed phases in the continuous phase; and
(c) at least substantially removing the second solvent from the double-emulsion to form the microparticles; and wherein the process is performed without high-shear mixing, wherein the process stream is not subsequently screened in the mixing environment.
10. The process of claim 9 , wherein the first solvent is an aqueous solvent.
11. The process of claim 9 , wherein the second solvent is an organic solvent.
12. The process of claim 9 , wherein the third solvent is an aqueous solvent.
13. The process of claim 9 , wherein the continuous phase further comprises a surfactant.
14. The process of claim 9 , wherein the polymer is a biodegradable polymer.
15. The process of claim 9 , wherein the polymer comprises poly(lactide), poly(glycolide), poly(caprolactone), or a copolymer or mixture thereof.
16. The process of claim 9 , wherein the agent is a bioactive agent.