Conclusions
Continuous manufacturing designs for liposomal drug products will help
meet the demand for these formulations, which are critical for future
drug delivery options. Understanding what impacts these continuous
manufacturing designs has benefit to their optimization. What is viewed
to be a minor phenomenon in a batch process design could have
significant impact to a continuous design. The deduction of an ethanol
concentration-dependent rejection coefficient in the batch process has
led to a greater understanding of how ethanol concentration will impact
a continuous TFF/ILDF process. Ethanol reduces and limits hollow fiber
permeability with the impact increasing with concentration. It was
determined that by diluting the post-liposome formation bulk and
reducing the initial ethanol concentration that fewer passes/stages of
ILDF and less buffer would be needed to achieve target ethanol removal.
In understanding this impact, continuous ILDF presents as a competitive
alternative to the batch process that can be scaled at will.