Thermal Analysis Tools for Physico-Chemical Characterization and Optimization of Perfluorocarbon Based Emulsions and Bubbles Formulated for Ultrasound Imaging

Abstract

Self-emulsifying microbubbles, especially designed to increase the contrast of ultrasound images by the inclusion of perfluorocarbon molecules, have been studied by thermal analysis techniques. The microbubbles were made of a blend of gas (20%), surfactants (50%) and water (30%). The surfactants were mixtures of polysorbate-85, Span-80, poloxamer 188, glycerol and fluorinated surfactant (Zonyl®). Microbubbles have been characterized by means of diffusion light scattering and optical imaging. The effect of Zonyl® on encapsulation rate, as well as gas vaporization temperature and gas release temperature, has been assessed by means of Differential Scanning Calorimetry (DSC) and Thermogravimetric Analyses (TGA). Microscopy and laser granulometry techniques have been also carried out for each formulation in order to determine the number of microbubbles and their size, respectively. Moreover, stability of the emulsions has been evaluated by DSC and confronted with the results obtained from the ultrasound experiments. Average microbubble concentrations of 7.2 × 107 and 8.9 × 107 per mL were obtained for perfluorohexane and perfluoropentane based emulsions, respectively. The present study demonstrates that the amount of encapsulated perfluorocarbon increases and the gas evaporation temperature decreases with the concentration of Zonyl®. Furthermore, the best ultrasound contrast images have been obtained in vitro with the samples containing the lowest Zonyl® concentration. An explication regarding the role of Zonyl® in the emulsion/microbubbles preparations is proposed here in order to optimize self-emulsifying microbubble formulation for pharmaceutical development.