Development of a continuous dense gas process for the production of liposomes

A new process called Continuous Anti-Solvent (CAS) process was developed for the production of liposomes using supercritical CO2. Unlike the current dense gas technologies, CAS method is a single step and continuous process. Preliminary experiments were conducted in semi-batch mode to determine the most suitable operating conditions (stirring speed = 225 rpm; water/lecithin mass ratio = 21) to ensure an efficient phase mixing in the autoclave. Then, two procedures were developed for the CAS process in the continuous mode. According to the results, the single exit procedure enhances the phase mixing in the autoclave with the formation of a CO2-in-water emulsion which is a good precursor to liposome formation. Liposomes prepared with the CAS method (P = 9 MPa; T = 308 K; CO2 flow rate = 0.3 kg h−1; organic solution flow rate = 240 mL h−1; water flow rate = 180 mL h−1) are spherical and multilamellar with a medium diameter included between 10 and 100 μm.

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► A single step and continuous process was developed for the production of liposomes using supercritical CO2 called the Continuous Anti-Solvent (CAS) process.
► The CAS process benefits from the effect of the Supercritical Anti-Solvent (SAS) process which ensures the micronization of the phospholipid matter.
► In the continuous mode, the initial formation of a homogeneous CO2-in-water emulsion in the autoclave brings about the formation of liposomes with unimodal size distribution.
► The CAS process enables the formation of spherical and multilamellar liposomes with a medium diameter included between 10 and 100 μm.