Pc. Sontum et al., EVIDENCE AGAINST MOLECULAR AGGREGATES IN CONCENTRATED-SOLUTIONS OF X-RAY CONTRAST-MEDIA, International journal of pharmaceutics, 169(2), 1998, pp. 203-212
In order to evaluate the possible existence of large molecular aggrega
tes in concentrated solutions of X-ray contrast media used for medical
imaging, a comprehensive study of the effect of the contrast medium c
oncentration on the osmolarity, light scattering and molecular diffusi
on has been performed for the two X-ray contrast media, Omnipaque (ioh
exol) and Visipaque (iodixanol). The measured change in osmolarity and
light scattering with increasing concentration of contrast medium was
well explained by solvent-solute and solute-solute interactions. Mini
ma were observed for both the concentration-normalized osmolarity and
the inverse of the concentration-nonnalized Rayleigh ratio, observatio
ns which are incompatible with the hypothesis of aggregation at higher
concentrations. From the observed minima, dynamic clusters containing
at maximum two to three molecules were demonstrated. The apparent mol
ecular diameter measured with dynamic light scattering, was found to b
e well predicted from the thermodynamic expression of the concentratio
n dependency of the mutual diffusion coefficient. The observed scatter
ing intensity was incompatible with an actual increase in the geometri
c size of the scatterers (i.e. aggregation) with increasing concentrat
ion. Contrary to the conclusions made by other investigators, the resu
lts presented clearly demonstrate the absence of large colloidal-like
structures or molecular aggregates' in the X-ray contrast media invest
igated. (C) 1998 Elsevier Science B.V. All rights reserved.