2025 AIChE Annual Meeting

(362g) Effect of Polysorbate 20 on Sterile Filtration of Nanoemulsions

Authors

Shreya Kapila - Presenter, Birla Institute of Technology and Science Pilani -
Milea M. Osmanski, Penn State University
Randy Soukup, Merck & Co.
Marissa Bradley, Merck & Co.
David Boyd, Merck & Co.
Andrew Zydney, Pennsylvania State University
Nanoemulsions (20–200 nm) have gained widespread use in the past two decades as vaccine adjuvants and advanced drug delivery systems for hydrophobic compounds. They are typically prepared through a multi-step emulsification process involving aqueous and organic phases with appropriate surfactants, forming nano-sized droplets. However, their size poses significant challenges for sterile filtration using 200 nm-rated sterilizing-grade filters, with deposition of the nanodroplets leading to yield loss and low capacity. This study investigates the impact of Polysorbate 20, one of the surfactants used to stabilize the nanoemulsion, on enhancing the sterile filtration performance.

Nanoemulsions composed of squalene and stabilized with Span 85 and Polysorbate 20 (Tween 20) were subjected to sterile filtration at a constant filtrate flux, with the transmembrane pressure (TMP) monitored as a function of volumetric throughput. Various sterile filters with different pore morphologies and surface chemistries were examined. Additional Polysorbate 20 was used to either prewet the sterile filter (during the initial buffer flush) or to adjust the surfactant concentration in the previously formed nanoemulsion.

When membranes were prewetted with surfactant-free buffer, filtration did not occur until the TMP exceeded a critical value (~25 psi for the Pall Supor polyethersulfone dual-layer filter), with this initial TMP corresponding to the force required to push the deformable nanoemulsion droplets through the membrane pores. However, prewetting with Polysorbate 20 significantly reduced the initial TMP by more than 50%, while also increasing the filtration capacity by more than a factor of twofold. This reduction in initial TMP was due to a change in hydrophilicity of the sterile filter, which was quantified using contact angle measurements. Prewetting with Polysorbate 20 reduced the contact angle from 46° ± 1° to 21° ± 1°. Further insights into Polysorbate 20 adsorption were obtained by FTIR through the presence of characteristic C–H (~2900 cm⁻¹) and C–O–C (~1050 cm⁻¹) stretching peaks. The addition of Polysorbate 20 to the previously formed nanoemulsion also increased the capacity of the sterile filter, likely due to interactions with both the nanoemulsion and the membrane. These effects were seen with a wide range of sterile filters having different pore morphologies and chemistries. The results provide valuable insights into the factors controlling the sterile filtration of nanoemulsions as well as simple strategies that can be used to optimize the sterile filtration performance in practical applications.