Analysis of process parameters on the characteristics of liposomes prepared by ethanol injection with a view to process scale-up: Effect of temperature and batch volume

Liposomes have been extensively used as carriers of several compounds, due to their structural versatility in terms of size, composition, surface charge, lamellarity, and facility to incorporate hydrophilic and hydrophobic substances. Among the methodologies for liposomes production, the ethanol injection technique is probably the most suitable for implementation at industrial scale, mainly due to its simplicity. The effects of the aqueous phase temperature and preparation volume on the characteristics of liposomes produced by this technique were evaluated, seeking to attain criteria for its implementation in large scale. The aqueous phase temperature significantly affects the final characteristics of liposomes obtained by this methodology. By varying this parameter, it is possible to control size distribution and polydispersity of the lipid vesicles. Subsequently, process scale-up was carried out using a 10-fold scale ratio. The adapted power per unit of volume (P/V) scale-up criterion showed to be appropriate to reproduce in larger scale the final characteristics of liposomes produced in smaller scale. The results demonstrate that using the ethanol injection technique, it is possible to obtain a relatively narrow distribution of small unilamellar vesicles, appropriately modulating the experimental conditions. Therefore, the preparation of vesicles with the desired diameter and size distribution was essentially fulfilled.

Research highlights▶ Aqueous phase temperature affects size distribution and polydispersity of liposomes. ▶ Process scale-up was carried out using a 10-fold scale ratio. ▶ Scale up criterion the power per unit of volume ratio (P/V) showed to be adequate. ▶ Modulations experimental conditions promote a narrow distribution of small vesicles.