The Significance of Particle/Globule-Sizing Measurements in the Safe Use of Intravenous Lipid Emulsions

ABSTRACT

Intravenous lipid emulsions (IVLEs) are an integral part of the clinical care of acutely ill patients who are unable to sustain nutrient homeostasis by mouth for protracted periods of time. They are oil-in-water emulsions stabilized by an emulsifier that imparts a net negative charge to the surface of the globules which stabilizes the dispersion. The mean droplet size of commercial IVLEs is approximately 300 nm. When the emulsion becomes unstable, these homogenously distributed droplets begin to aggregate and ultimately coalesce into large fat globules. Phase separation typically occurs when the volume-weighted percent fat greater than five micrometers (PFAT >5 μm) exceeds 0.4% of the total lipid present in a formulation. Moreover, when the size of the droplets reaches a dimension of 5 μm or larger, the infused globules may lodge into the pulmonary capillaries and produce a fat embolism syndrome. Thus, in the assessment of stability and the subsequent safety of IVLEs, any particle sizing measurement technique must be able to reliably quantify the volume-weighted fraction of the coalesced fat globules that statistically comprise the distribution tail of the largest diameter droplets of the emulsion. Of the four common particle sizing methods reviewed, light obscuration or light extinction, is the only one that measures fat globules accurately enough to determine the clinical safety of IVLEs.

Keywords:

• Intravenous fat emulsion
• Large diameter tail
• Emulsion stability

Acknowledgments