Optimizing the Filtration of Liposomes Using Sterilizing-Grade Filters.

Abstract

Liposomes are increasingly being investigated and implemented as injectable drug delivery systems. The preferred method for sterilizing injectable drug formulations using liposomes is to use filtration. However, because of the size of liposomes and their physicochemical properties, this can be challenging with sterilizing-grade filters rated at 0.2 µm. Filter validation studies with injectable liposomes have shown a higher likelihood of premature filter blockage and bacterial penetration compared to other parenteral drug types. Consequently, a greater understanding of the sterilizing filtration of liposomes is required so that appropriate decisions are made concerning the selection and validation of sterilizing-grade filters for these applications. In this work, Lipoid S100 liposomes were produced using a microfluidization technique without any encapsulated drug (empty) to investigate their filtration through a polyethersulfone filter. In order to improve the sterilizing-grade filtration of liposomes, optimization of both the filtration process and the formulation characteristics is important. To show this, the effect of the different filtration conditions/parameters (prefiltration, serial filtration, differential pressure, inlet pressure) and liposome characteristics such as size and size distribution on filtration were examined. For example, by decreasing the size of the liposome from 179.0 to 127.3 nm, the volumetric throughput (L/m2) was increased by more than 40-fold. Or by increasing the differential pressure, the volumetric throughput was improved significantly by more than 18-fold (0.7 to 4.1 bar) and in another experiment by more than 10-fold (0.3 to 2.1 bar). In addition, the benefit of using higher differential pressure on the liposome transmission through various sterilizing-grade membranes was shown.