COMPOSITIONAL HETEROGENEITY IN PARENTERAL LIPID EMULSIONS AFTER SEDIMENTATION FIELD-FLOW FRACTIONATION

This study examines the size and compositional heterogeneity of partic les in a commercial lipid emulsion (Intralipid) before and after equil ibration with penclomedine, a highly lipophilic cytotoxic agent. Emuls ions were fractionated by sedimentation field-flow fractionation (sedF FF), and particle sizes of the monodisperse fractions were determined by photon correlation spectroscopy. The triglyceride (TG), phosphatidy lcholine (PC), and penclomedine (in drug loaded emulsions) contents in each fraction were determined by HPLC. The aqueous-entrapped volume w ithin Intralipid was determined to be approximate to 10% by size-exclu sion chromatography using [H-3]mannitol. Thirteen sedFFF fractions col lected from the drug free emulsions yielded particles ranging in size from 154 to 423 nm. Total channel recoveries were 89% and 95% for TG a nd PC, respectively. Apparent particle densities varied significantly with size, suggesting heterogeneity in composition as confirmed by PC/ TG mass ratios which varied dramatically. Computer fits of the distrib ution profiles suggested populations of phospholipid vesicles and oil droplets containing excess phospholipid in addition to classical emuls ion droplets. Drug loading induced a significant shift of the predomin ant triglyceride containing population to a larger particle size. The penclomedine distribution profile closely mimicked that of the TG rath er than the PC fraction. These studies suggest the need to consider no t only size distribution but also compositional distribution in charac terizing parenteral emulsions.