Preparation of liposomes at large scale using the ethanol injection method: Effect of scale-up and injection devices

Abstract

In the present study, the preparation of liposomes using the ethanol injection technique was reported for volumes from 60mL to 3L. Experimental set-up with different scales and injection devices have been tested: (1) a device using a syringe for injection; (2) an experimental set-up using two pumps for injecting both organic and aqueous phases through a Shirasu Porous Glass (SPG) membrane; (3) a pilot plant using a tube dipping into the aqueous phase for injection of the organic phase; (4) a pilot plant using two pumps for injection of both organic and aqueous phases through the SPG membrane. The liposome preparations obtained were characterized for their size, polydispersity index (PDI), zeta potential, and morphology by transmission electronic microscopy (TEM). Two formulations have been tested: drug-free liposome formulation and α-tocopherol-loaded liposome formulation. For both formulations, it was shown that all experimental set-ups were appropriate for the preparation of small vesicles having narrow size distributions, with good reproducibility and stability. The pilot plant using a membrane for injection improves micromixing of the organic phase into the aqueous phase and therefore optimizes the preparation time. Evaporation of ethanol performed directly on the pilot plant has the advantages of being an easy and continuous process.