Supercritical PArticle formation (SPAF) process for the versatile production of ready-to-market drug delivery systems

• Production of liposomal powder stable up to 24 months. • Optimization of Drug-to-Lipid Ratio for high encapsulation efficiency. • 25 kg pilot-scale production batch for industrial application. • Controlled and narrow particle size distribution via spray drying. • Total absence of bacterial growth, pesticides and toxic metals. Supercritical PArticle Formation has been proposed for the entrapment of ferrous sulphate in liposomes, overcoming drawbacks linked to conventional processes, such as residual solvents and low versatility. The innovation of this process was the combined integration of supercritical assisted production with drying techniques (freeze and spray-drying) and final drum-grinding, being effective in preserving active ingredients while eliminating liquid content. Liposomes powder was stable over 24 months, mean size down to 3.5 µm was achieved, with a Lipid/Drug ratio of 6. Encapsulation efficiency up to 94 ± 4 % was obtained without significant loss during drying. Supernatant and lipidic pellets were separated and analyzed, demonstrating presence of lightweight floating liposomes in the aqueous part and larger lipo-complexes among the solids. During the production of a pilot-scale batch of 25 kg, liquid-to-powder yield of 0.179 kg/L was obtained. Drying was successful to produce narrow vesicles in absence of pesticides, bacteria and heavy metals.