Optimizing sterile filtration of nanoemulsions through proper choice of prefilter properties.

Nanoemulsions, with droplet sizes between 20 and 200 nm, have emerged as a promising vaccine adjuvant and drug delivery system, enhancing the solubility of hydrophobic drugs for diverse applications. Sterile filtration of nanoemulsions is particularly challenging due to the similar size between the nanodroplets and the 0.2 μm nominal pore size rating of sterile filters. One approach to reducing membrane fouling, and enhancing filtration capacity and yield, is to employ an appropriate prefilter, but there are currently no clear guidelines on how to select the prefilter pore size, chemistry, or morphology for sterile filtration of nanoemulsions. This study examined the performance of a range of prefilters with varying pore morphologies and surface chemistries. Sessile drop contact angles were used to evaluate the prefilter hydrophobicity, and bubble point and mercury intrusion porosimetry were used to evaluate the pore characteristics of the different prefilters. The best performance was achieved using a relatively hydrophobic 0.45 μm prefilter made of polyvinylidene fluoride but modified with a somewhat hydrophilic (oxygen-containing) coating. This prefilter reduced the surface tension of the nanoemulsion and provided more than a 2-fold increase in capacity for a variety of sterile filters. These results provide critical insights into the factors influencing nanoemulsion filtration and offer a framework for selection of appropriate prefilters in biopharmaceutical manufacturing.