Mapping size distributions of parenteral fluorocarbon emulsions by a novel method of centrifugal sedimentation followed by densitometry.

A novel method for characterization of size distributions of parenteral fluorocarbon emulsions is described. Prepared emulsions were centrifuged to sediment droplets above predetermined diameters out of a known supernatant sample volume using the Bostok-Stoke's equation. Centrifugation times may be calculated using centrifuge parameters and physical properties of the fluorocarbon oil phase and the dispersion medium. The fluorocarbon content of the supernatant sample volume at successive centrifugation times was determined both by densitometry and by Gas Chromatography. A close correlation was found between the two methods. The density data was processed and converted into a volume distribution histogram by means of a program written in BASIC. The speed, simplicity of use, non reliance on costly equipment and good correlation to absolute particle counting methods makes the density method suitable for submicron size characterization.

The influence of manufacturing parameters on the formation and growth on autoclaving of a 40% V/V Bis-Perfluorobutylethene emulsion.

The influence of different process variables on the number of large particles before and after autoclaving of a 40% V/V Bis-Perfluorobutylethene emulsion stabilized by egg yolk lecithin, made isotonic with blood, was examined. The concentration of emulsifier, emulsification and autoclaving time and temperature, fill volume and the cooling gradient applied to the emulsion after autoclaving all affect the number of large droplets and hence the stability and acceptability of the finished product. This work suggests that validation of equipment and process to very exacting specifications and strict adherence to specified manufacturing protocol is essential for the reproducible production of fluorocarbon emulsions acceptable for intravenous administration.