Medium-chain triglycerides based oil-in-water microemulsions for intravenous administration: formulation, characterization and in vitro hemolytic activities

To obtain o/w microemulsions with minimized surfactant content, three parameters: the minimum surfactant content required to solubilize 4% oils (MIS), the maximum oil content solubilized by 20% surfactants (MAO) and the minimum surfactant content required to solubilize equal amounts of oil phase and aqueous phase (MISE) were used to evaluate the oil-solubilization capacity of the surfactant systems containing at least one surfactant and one cosurfactant. After initial screening, the surfactant system of Cremophor EL-lecithin-ethanol was chosen for further study due to its strong oil-solubilization capacity and approval for intravenous administration. Increased content of Cremophor EL in the surfactant system of Cremophor EL-lecithin-ethanol resulted in enhanced oil-solubilization capacity. Comparatively, ethanol presented the opposite effect on oil-solubilization capacity of the surfactant system. However, it was difficult to form o/w microemulsions in the absence of ethanol. A series of medium-chain triglycerides-loaded microemulsions (MCT-MEs) containing Labrafac cc were prepared based on the above optimized surfactant system. The average droplet sizes of MCT-MEs were around 20nm, which increased slightly when being diluted by water but remained unchanged by phosphate buffer solution (pH 7.4) with or without 0.5% Tween-80 except to 1,000-fold. Hemolytic activities of MCT-MEs were enhanced when propyl glycol-water was used as outer aqueous phase or the surfactant content were increased. Hemolytic action scarcely occurred when microemulsions were diluted to more than 10-fold in normal saline. Drug-loaded MCT-MEs exhibited similar physicochemical characteristics with drug-free MCT-MEs in terms of droplet size, stability and hemolytic activity.