Modulating Membrane Surface Properties via Prewetting With Polysorbate 20 to Improve Sterile Filtration of Nanoemulsions

Abstract

Nanoemulsions are promising vaccine adjuvants and drug delivery vehicles. However, sterile filtration of nanoemulsion formulations remains challenging because of the large size of the nanodroplets. This study investigates how prewetting the sterile filters with Polysorbate 20 (PS20) modulates the surface properties and enhances filtration performance of a range of sterile filters using a squalene-based nanoemulsion stabilized with PS20 and Span 85. FTIR and contact angle measurements were used to evaluate the change in filter surface chemistry. Prewetting with PS20 reduced the buffer permeability, but it generally increased the filtrate flux with the nanoemulsion, often by as much as a factor of two, due to the reduction in frictional interactions between the surfactant-coated nanodroplets and the pretreated membrane. PS20 also reduced the extent of pore blockage, leading to a dramatic increase in capacity with most sterile filters. For example, the capacity of the Millipore Express Plus increased by nearly 100-fold, compared to only a 2-fold increase in capacity for the dual-layer Pall Supor 0.8/0.2 µm filter, even though both filters are polyethersulfone. This work highlights the importance of membrane surface chemistry and the potential for modulating filter properties by prewetting with surfactants to improve the sterile filtration of nanoemulsion-based drug products.