Flux and fouling behavior during constant pressure sterile filtration of nanoemulsions

Abstract

Nanoemulsions with droplet diameters from 20 to 200 nm have emerged as attractive adjuvants in the development of novel vaccines and as an advanced method of drug delivery for hydrophobic drugs. However, the large size of the nanoemulsion droplets leads to very low capacities during the final sterile filtration step used to ensure sterility of parenteral drug products. The objective of this study was to examine the sterile filtration of a model nanoemulsion made using squalene as the oil and Tween 20 and Span 85 as stabilizing surfactants. Data were obtained with different commercial sterile filters with different morphology and chemistry during constant pressure filtration. In each case, there was essentially no filtration until the transmembrane pressure exceeded a critical value related to the force required to push the deformable nanoemulsion droplets through the membrane pores. The filter capacity increased with increasing pressure, going from 700 g/m² at 140 kPa to 1300 g/m² at 280 kPa for a dual layer polyethersulfone sterile filter, with the flux decline well described by the complete pore blockage model. The dual layer asymmetric membranes showed much higher capacities than corresponding single layer filters due to the effectiveness of the upper layer in removing larger nanoemulsion droplets that would otherwise block the pores of the sterile filter. The capacity of the different sterile filters was also well-correlated with the initial filtrate flux, with both of these parameters governed by the pore size distribution and surface chemistry of the filters. These results provide important insights into factors controlling the sterile filtration of highly concentrated nanoemulsions used in the formulation of vaccines and drug products.