Table 6.

Select Methods of Liposome Preparations and Their Advantages and Disadvantages in Scale-Up Procedures

	Basic Technique	Advantages for Scaling	Disadvantages for Scaling	Scalability Potential
Formulation method
Thin film hydration	Solvent evaporation followed by rehydration in aqueous phase	Simple	Requires size reduction Equipment size is volume dependent	Suitable for small to mid-size batches
Reverse-phase evaporation	Mixing of immiscible solvent with aqueous phase to form emulsion followed by evaporation of solvent	Simple	Multistep process Size reduction required	Suitable for small to mid-size batches
Solvent injection	Injection of miscible solvent (generally ethanol) into aqueous phase	Single-step process Continuous processing	Presence of solvent without postremoval Not all lipids/drugs dissolve in ethanol	Very good
Detergent depletion (dialysis)	Mixed-micelle formation with detergent followed by detergent dilution or removal	Gentle	Presence of detergent Multistep process	Good for sensitive proteins and oligonucleotides
Supercritical fluid	Solvation of lipids in supercritical carbon dioxide followed by injection into low-pressure aqueous phase	No organic solvent Sterility	Expensive equipment	Good potential
Size reduction
Sonication	Ultrasonic energy to disrupt vesicles	Simple	Poor reproducibility Polydisperse population	Suitable for small batches only
High-pressure homogenization	High-velocity collisions mechanically disrupt vesicles	Monodisperse population Reproducible Continuous processing	Volume loss Limited size control	Very good
Low-pressure extrusion	Forcing through a filter of defined pore size	Monodisperse population Reproducible Continuous processing	Clogging of membrane Difficult to maintain temperature	Good for small to mid-size batches