Preparation of drug-in-cyclodextrin-in-liposomes at a large scale using a membrane contactor: Application to trans-anethole

• Drug-in-cyclodextrin-in-liposomes were applied to encapsulate trans-anethole.
• Membrane contactor and a pilot plant were used for liposome production at large scale.
• Nanometric oligolamellar and spherical shaped vesicles were stable.
• A small amount of trans-anethole was released after 21 days at 4 °C.

The present study aimed to prepare liposomes loaded with cyclodextrin/drug inclusion complexes at a pilot scale based on the ethanol injection technique. Anethole (ANE), a major component of anise and fennel essential oils, was used as a model of a volatile and highly hydrophobic drug. Membrane contactor (600 mL) and a pilot plant (3 L) were used for liposome production. The liposome preparations obtained were characterized for size, polydispersity index, zeta potential, morphology, stability and ANE release rate. All experimental set-ups were shown to be appropriate for the preparation of small, multilamellar vesicles with narrow size distribution and good stability at 4 °C. The drug release study showed that only a small amount of ANE was released from liposome formulations after 21 days of storage at 4 °C. The loading rate of ANE was higher when ethanol was evaporated directly on the pilot plant compared to a rotary evaporation.