Globule-size distribution in injectable 20% lipid emulsions: Compliance with USP requirements

Purpose. The compliance of injectable 20% lipid emulsions with the globule-size limits in chapter 729 of the U.S. Phormacopeia (USP) was examined. Methods. As established in chapter 729, dynamic light scattering was applied to determine mean droplet diameter (MDD:), with an upper limit of 500 nm. Light obscuration was used to determine the size of fat globules found in the large-diameter tail, expressed as the volume-weighted percent fat exceeding 5 lam (PFAT(5)), with an upper limit of 0.05%. Compliance of seven different emulsions, six of which were stored in plastic bags, with USP limits was assessed. To avoid reaching coincidence limits during the application of method II from overly concentrated emulsion samples, a variable dilution scheme was used to optimize the globule-size measurements for each emulsion. One-way analysis of variance of globule-size distribution (GSD) data was conducted if any results of method I or II exceeded the respective upper limits. Results. Most injectable lipid emulsions complied with limits established by USP chapter 729, with the exception of those of one manufacturer, which failed to meet the PFAT(5) limits as proposed for three of the emulsions tested. In contrast, all others studied (one packaged in glass and three packaged in plastic) met both criteria. Conclusion. Among seven injectable lipid emulsions tested for GSD, all met USP chapter 729 MDD requirements and three, all from the same manufacturer and packaged in plastic, did not meet PFAT(5) requirements.