In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly watersoluble drugs. The use of water-miscible nonaqueous solvents is therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies.

The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme).