A quality by design approach for liposomes production by innovative method using supercritical fluids: which parameters use to obtain good physicochemical characteristics?

Liposomes are nanoparticles made of phospholipids, able to encapsulate many active molecules, protecting and transporting them in a targeted way. Liposomes are thus widely studied as vectors of numerous active molecules, improving their therapeutic window. However, the usual production methods at the laboratory scale have many disadvantages and are generally difficult to transfer to the industrial scale under GMP conditions [1], [2].
Supercritical fluids are increasingly used in the pharmaceutical industry. One of the pharmaceutical applications of supercritical fluids is the production of particles. For the liposomes production, the use of supercritical CO2 as a dispersing agent has been preferred because of the total absence of organic solvent. Since this process involves many parameters such as pressure, temperature, stirring speed, lipid concentration, volume and contact time, a quality by design approach was used in order to determine the influence of each parameters on the physicochemical properties of liposomes such as the size and the polydispersity.
These experimental analyses helped us to find two production areas. These conditions were validated with five different liposome formulations regarding the size and polydispersity expectations. We will now focus on the impact of each parameter on the physicochemical properties of liposomes but also their impact on the integrity of the phospholipids used.