There are many reasons for experiencing difficulty when sonicating lipid suspensions. The following list are some of the more common problems that may occur:

• In general, PC is more difficult to sonicate than charged lipids.
• Lyophilized powders disperse more readily and sonicate easier than lipid films dried from organic solvent.
• PE membranes will aggregate to form a flocculant.
• Charged membranes (PS, PG, PI, PA, etc.) will aggregate in the presence of divalent cations (e.g., calcium).