Abstract
Liposomal drug products are playing an increasing role in the field of
drug delivery. With this increased demand comes the need to increase the
capabilities and capacity of manufacturing options. Continuous
manufacturing techniques present a significant opportunity to address
these needs for liposomal manufacturing processes. Liposomal
formulations have unique considerations that impact translation from
batch to continuous process designs. This article examines aspects of
converting to a continuous design that were previously viewed as
inconsequential in a batch process. The batch process involves the
removal of ethanol through tangential flow filtration (TFF). Ethanol was
found to reduce the permeability of the hollow fibers used for TFF. This
effect was determined to have minimal impact on the overall batch
process design but considerable influence on the design of continuous
TFF such as inline diafiltration (ILDF). Using a pilot scale setup,
ethanol was found to decrease permeability in an inverse manner to
ethanol concentration. Further assessment found that dilution of the
ethanol levels prior to diafiltration can significantly reduce the
amount of ILDF stages needed and that a continuous design requires less
buffer to the commensurate batch design.