Benchmarking of Sterilizing-Grade Filter Membranes with Liposome Filtration

Abstract

Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells. The sterility of such liposome solutions is typically ensured using 0.2 μm-rated sterilizing-grade membranes, but due to the high viscosity and low surface tension of these formulations, they can cause premature blocking and increased risk of bacterial penetration through a 0.2 μm sterilizing-grade membrane. The low surface tension of liposome solutions affects the contact angle with membrane and reduces bubble point, leading to bacterial penetration through the membrane. This poses a great challenge to select an appropriate sterilizing-grade membrane for a given process and for filter manufacturers to develop a sterilizing-grade membrane that specifically addresses these needs. In this study, the influence of different variables that could affect the total throughput and bacterial retention performance of different membrane types on processing of liposome solutions was evaluated. Based on the results, we conclude that the membrane properties, for example, surface porosity, surface tension, pore size, symmetry/asymmetry, hydrophilicity and liposome properties (e.g., composition, lipid size, and concentration) affect bacterial retention and total throughput capacity. Process parameters such as temperature, pressure, and flow should also be optimized to improve process efficiency. Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells. Liposome solution cause premature blocking and increased risk of bacterial penetration through a 0.2 μm sterilizing-grade membrane due to their high viscosity and low surface tension. In this study, we demonstrated the total throughput and bacterial retention performance of different sterilizing-grade membranes with liposome solution. Based on the results, we conclude that some sterilizing-grade membranes yield less throughput and bacterial retention compared to other membranes. This is due to liposome formulation and membrane properties. Therefore, it is important to identify the product formulation and membrane properties before selection of a suitable sterilizing-grade filter for a given process application to ensure expected throughput and bacterial retention.

Liposomes as vehicles for topical ophthalmic drug delivery and ocular surface protection

“…However, some difficulties that are related to viscosity and surface tension of the formulation can lead to a quick blockage of the filtration membrane, and an increment in permeation of bacteria and pathogens may occur. Therefore, it is important to choose the most appropriate membrane depending on the conditions for the liposomal sample [136]. For that reason, although these conventional methods might be enough, a final sterilizing process is still required by some manufacturers.…”

Lipid-Based Vesicles: a Non-invasive Tool for Transdermal Drug Delivery

“…These membranes are usually made up of polycarbonate or cellulose. Vesicles smaller than 200 nm can be filtered through these membranes [112]. Thermolabile loaded vesicles are mainly sterilized by this technique.…”

Pressure‐dependent fouling behavior during sterile filtration of mRNA‐containing lipid nanoparticles

“…The authors hypothesized that the increase in capacity with increasing pressure was due to either a change in liposome size and shape or reduced interactions with the membrane pores associated with the shorter residence time, although no detailed analysis of these phenomena was provided. Although several studies have described the sterile filtration of liposomes (Folmsbee & Moussourakis, 2012; Johnson et al, 2021; Singh et al, 2018; Toh & Chiu, 2013; Zourna et al, 2021), there do not appear to be any published data on the sterile filtration of mRNA‐LNPs or any other LNPs.…”

“…Although several studies have described the sterile filtration of liposomes (Folmsbee & Moussourakis, 2012;Johnson et al, 2021;Singh et al, 2018;Toh & Chiu, 2013;Zourna et al, 2021), there do not appear to be any published data on the sterile filtration of mRNA-LNPs or any other LNPs.…”