Sterilization of Contrast Media (Isovist) Containing Liposomes by Ethylene Oxide

Abstract

Liposomes containing Isovist were prepared by controlled detergent dialysis as well as by reverse phase evaporation. After preparation these liposomes were lyophilized and then submitted to sterilization by ethylene oxide. Prior to lyophilization, trehalose was added as a protective agent to preserve the size of the liposomes. After each step in the preparation size distribution was determined by photon correlation spectroscopy. The computer program CONTIN was adapted for the data analysis and proved to be applicable for polydisperse solutions of liposomes. Neither freeze-drying nor sterilization had negative effects on the morphological quality of the samples when using 4 g of trehalose per 1 g of lipid. In addition, the quality of the liposomes was controlled by scanning electron microscopy. At the end of seven days, no growth of microorganisms occurred in any of the samples.