(695f) Enhancing Sterile Filtration of Nanoemulsions Using Prefiltration

Nanoemulsions are currently used as adjuvants in the development of novel vaccines and as an advanced method of drug delivery which act as a delivery system for hydrophobic drug products. Nanoemulsions are prepared by a multi-step process involving the mixing of immiscible aqueous and organic phases, typically in the presence of one or more surfactants, resulting in a suspension with nano-sized droplets with diameters of 20 to 200 nm. This can create significant challenges for the final sterile filtration step which uses sterilizing grade filters that are rated with a 200 nm pore size. The objective of this study was to examine the sterile filtration of a model nanoemulsion, with a specific focus on the opportunity of enhancing the product yield and filter capacity by appropriate choice of a prefilter.

Experiments were performed with nanoemulsions made using squalene with Tween 20 as a surfactant. Sterile filtration was performed at a constant filtrate flux, with the transmembrane pressure monitored as a function of the volumetric throughput. A number of sterile filters and prefilters were examined with different pore morphologies and surface chemistries. In each case, a significant transmembrane pressure (TMP) was required to obtain any flux through the membrane, with typical values for the Pall Supor (polyethersulfone) dual-layer filter of around 25 psi. This large initial TMP reflects the force required to deform and “push” the nanoemulsion droplets through the small pores of the sterile filter. The initial TMP could be significantly reduced by prefiltering the nanoemulsion through an appropriate pore size prefilter, with the best performance obtained using 0.45 µm polyvinylidene fluoride (PVDF) prefilters. The TMP increased nearly linearly with volumetric throughput, with the slope, and thus the capacity, dependent on the properties of both the sterile filter and the prefilter. Contact angle measurements using the sessile drop method with water revealed a contact angle of 120° ± 3° (θ > 90°) for Sterlitech PVDF, indicating it possesses a hydrophobic surface. Even though the water permeability of sterlitech PVDF prefilter is very less (< 300 LMH/psi) compared to > 2000 LMH/psi for PES filters owing to their less hydrophilic surface properties. Bubble point tests reveal it has the largest pore size (1.72 µm) despite its rating as 0.45 µm, compared to all other prefilters. Most hydrophobic prefilters, like PVDF, showed lower initial TMP and higher capacity, possibly due to their less hydrophilic nature, as indicated by contact angle measurements and XPS analysis, aiding in easier passage for oil droplets through the filter. Thus, a combination of differences in pore size and surface properties play a role in determining the prefiltration performance. These results provide important insights into factors controlling the sterile filtration of nanoemulsions as well as a framework for the design and optimization of improving sterile filtration processes.