Droplet-size distribution and stability of lipid injectable emulsions

Abstract

The droplet-size distribution (DSD) and stability of multiple lots of lipid injectable emulsions were studied. A total of 234 commercial batches of Intralipid (Fresenius Kabi, Uppsala, Sweden) were characterized, and the influence of the emulsions' oil content on samples packaged in single- and three-chamber bags was tested. Larger-sized lipid particles were quantified using a single-particle optical sensing device. For this test, a 1-mL sample of each product was analyzed using a dilution factor of 90-400, depending on oil concentration. Analyses were performed in triplicate. Measurements were also performed in single-bag products after up to six months of storage at 23-27 degrees C and 40 degrees C. DSD measurements were determined by laser light scattering. Droplet sizes were determined using laser diffraction, with aliquots of emulsions carefully dispersed step by step applying gentle agitation. Standard deviation analyses were performed using analysis of variance. The volume-weighted percentage of fat droplets greater than 5 mum (PFAT(5)) values of all samples were below the large-globule size limit (0.05%) established by the United States Pharmacopeia for lipid injectable emulsions. Container volume did not significantly influence globule size, though a slight tendency for larger bag volumes to have larger PFAT(5) values was apparent. PFAT(5) and mean volume diameter values increased with oil concentration in the emulsion. Storage time and temperature had no significant effect on PFAT(5) and mean droplet-size values. Multiple lots of a lipid emulsion were found to have acceptable PFAT(5) and mean droplet-size values, regardless of oil content, container size, or storage time and tempearture.