Compositional heterogeneity in parenteral lipid emulsions after sedimentation field flow fractionation.
This study examines the size and compositional heterogeneity of particles in a commercial lipid emulsion (Intralipid) before and after equilibration with penclomedine, a highly lipophilic cytotoxic agent. Emulsions were fractionated by sedimentation field-flow fractionation (sedFFF), and particle sizes of the monodisperse fractions were determined by photon correlation spectroscopy. The triglyceride (TG), phosphatidylcholine (PC), and penclomedine (in drug loaded emulsions) contents in each fraction were determined by HPLC. The aqueous-entrapped volume within Intralipid was determined to be approximately 10% by size-exclusion chromatography using [3H]mannitol. Thirteen sedFFF fractions collected from the drug free emulsions yielded particles ranging in size from 154 to 423 nm. Total channel recoveries were 89% and 95% for TG and 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 distribution profiles suggested populations of phospholipid vesicles and oil droplets containing excess phospholipid in addition to classical emulsion droplets. Drug loading induced a significant shift of the predominant triglyceride containing population to a larger particle size. The penclomedine distribution profile closely mimicked that of the TG rather than the PC fraction. These studies suggest the need to consider not only size distribution but also compositional distribution in characterizing parenteral emulsions.
Venkatesh
S
S
Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Li
J
J
Caldwell
K D
KD
Anderson
B D
BD
D000970:Antineoplastic Agents / Q000032:analysis; D005591:Chemical Fractionation / Q000379:methods; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions / Q000032:analysis; D005217:Fat Emulsions, Intravenous / Q000032:analysis*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D010847:Picolines / Q000032:analysis; D014280:Triglycerides / Q000032:analysis; D014867:Water / Q000032:analysis
D000970:Antineoplastic Agents; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010713:Phosphatidylcholines; D010743:Phospholipids; D010847:Picolines; D014280:Triglycerides; D014867:Water; C058388:penclomedine