Clove essential oil-in-cyclodextrin-in-liposomes in the aqueous and lyophilized states: From laboratory to large scale using a membrane contactor

• Preparation of clove essential oil-in-cyclodextrin-in-liposomes (DCL) at laboratory and large scales.
• Freeze-drying of liposomes encapsulating inclusion complex of a volatile hydrophobic compound.
• DCL formulations were stable in aqueous dispersions after 1 month of storage at 4 ̊C and in lyophilized forms.
• DCL formulations maintained the DPPH scavenging activity of free clove essential oil, free eugenol and their inclusion complexes.

This work is dedicated to prepare liposomal dry powder formulations of inclusion complexes of clove essential oil (CEO) and its main component eugenol (Eug). Ethanol injection method and membrane contactor were applied to prepare liposomes at laboratory and large scale, respectively. Various liposomal formulations were tested: (1) free hydroxypropyl-β-cyclodextrin loaded liposomes; (2) drug in hydroxypropyl-β-cyclodextrin in liposomes (DCL); (3) DCL2 obtained by double loading technique, where the drug is added in the organic phase and the inclusion complex in the aqueous phase. Liposomes were characterized for their particle size, polydispersity index, Zeta potential, morphology, encapsulation efficiency of CEO components and Eug loading rate. Reproducible results were obtained with both injection devices. Compared to Eug-loaded liposomes, DCL and DCL2 improved the loading rate of Eug and possessed smaller vesicles size. The DPPH
• scavenging activity of Eug and CEO was maintained upon incorporation of Eug and CEO into DCL and DCL2. Contrary to DCL2, DCL formulations were stable after 1 month of storage at 4 °C and upon reconstitution of the dried lyophilized cakes. Hence, DCL in aqueous and lyophilized forms, are considered as a promising carrier system to preserve volatile and hydrophobic drugs enlarging their application in cosmetic, pharmaceutical and food industries.