A method for the early evaluation of the effects of storage and additives on the stability of parenteral fat emulsions.

Abstract

The combination of sedimentation field-flow fractionation (SedFFF) and photon correlation spectroscopy (PCS) is shown to provide a detailed record of the droplet sizes present in fat emulsions commonly used in parenteral nutrition. The technique presented has been used to record size distribution data for a particular emulsion (Liposyn-II), demonstrating its high stability and lot-to-lot uniformity. The technique is also able to demonstrate how additions of small amounts of electrolytes [0.45% (w/v) NaCl, 0.05% (w/v) CaCl2] tend to destabilize the emulsion, suggesting some caution in the use of total parenteral nutrition (TPN) mixtures. In contrast, a 1:1 mixture with human serum caused no sign of instability in the Liposyn-II. Using the emulsion as a carrier for lipophilic drugs necessitates adding solutions of the drug in nonaqueous solvents, such as DMSO (dimethyl sulfoxide). This solvent's destabilizing effect results in a droplet coalescence that becomes severe after 3-5 days following a 10% (v/v) addition, while a 5% (v/v) addition reaches the same level of coalescence in 10 days.