Membrane Separation in Supercritical Antisolvent Process for Nanoparticle Production
Type of DegreeThesis
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In supercritical antisolvent process to produce pharmaceutical nanoparticles, drug solution is injected into supercritical carbon dioxide. CO2 rapidly extracts the solvent, causing the drug to precipitate as micro- and nano-particles. A portion of drug dissolves in CO2/organic solvent mixture. For the recovery of drug nanoparticles from the precipitation vessel, CO2/organic solvent is removed through a filter. As much as 50% of the drug is typically lost in the process, in dissolved and un-retained particle forms. Hence a better method to separate CO2/organic solvent is needed. In this work, a polymer membrane based separation of CO2/organic solvent is proposed and tested. Gas and vapor separations using non-porous polymer membranes have been brought to focus in the past 30 years. Very recently, amorphous Teflon (TeflonAF, DuPont, Wilmington, DE) polymers have been introduced which are copolymers consisting of 2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole (PDD) and tetrafluoroethylene (TFE). Teflon AF 2400 contains 87 mol% PDD and 13 mol% TFE with Tg = 240 oC, whereas Teflon AF 1600 contains 65 mol% PDD and 35 mol% TFE with Tg = 160 oC. Both the copolymers have a high temperature stability and chemical resistance, as well as high free volume compared to the conventional glassy polymers. Permeability coefficients of CO2 in Teflon AF 2400, Teflon AF 1600, and poly(tetrafluoroethylene) (PTFE) are measured, at varying feed pressure and temperature. The permeability increased in the order of PTFE < Teflon AF 1600 < Teflon AF 2400. This can be explained by the fact that PTFE is a semicrystalline polymer and Teflon AFs are glassy polymers with a high free volume. In addition, the reuse of the membrane for second and third time resulted in enhancement of the permeability, which can be attributed to the CO2 plasticization of the membrane. Further understanding of the transport of CO2 through the membranes is investigated by applying solution-diffusion model. In the presence of CO2, acetone solvent has a high permeability through Teflon AF. And no permeability of larger drug molecule tetracycline is observed through Teflon AF when dissolved in acetone.