Liposome attracts increasing attention in the medical and pharmaceutical fields as it is a potential candidate for the carrier of hydrophilic pharmaceuticals. A novel flow process for liposome production in a microfluidic tube using supercritical CO2 (scCO2) named as LipTube has been developed in this work. A micro-mixing in the flow process was used for the continuous and efficient formation of water-in-scCO2 (w/scCO2) emulsion, as well as entrapment of the pharmaceutical compound, timolol maleate. Additionally, water droplets in w/scCO2 emulsion with lecithin can be transported into the aqueous phase in the slug flow. The effects of several operating parameters such as lecithin concentration, co-solvent species, and the flow rate on the liposome formation were investigated. As a result, liposomes were successfully formed in the flow process continuously, and the size controllability ranging from 80 nm to 3.0 μm was achieved by changing the co-solvent flow rate. The encapsulation efficiency of pharmaceutical compounds in liposomes was also improved to about 80% by changing the co-solvent flow rate. The mechanism of remarkable size controllability and the high encapsulation efficiency were discussed based on the equilibrium concentration of co-solvents in the aqueous phase with scCO2. It is suggested that the viscosity of the aqueous phase is the critical factor in controlling the size and encapsulation efficiency of the liposome formed in the LipTube process.

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