In formulating eutectic media, the role of solvent adjuvant is not well understood in depressing the melting temperature of a binary substrate mixture (T-MB). Here, we demonstrated the effect of solubility on the depression of T-MB by using combinatorial model mixtures of N-benzyloxycarbonyl-L-Asp(CBZ-L-Asp) with either an L-amino acid or a D-sugar in different solvent adjuvants. When CBZ-L-Asp was mixed with an individual L-amino acid at an equi-molar ratio, T-MB values varied approximately from 34 to 113 C according to the hydrophobicity of adjuvants. Similarly. CBZ-L-Asp/D-sugar mixtures showed large variations of T-MB values approximately from 43 to 112 degrees C according to the hydrophobicity of adjuvants. In the water adjuvant. T-MB values in both CBZ-L-Asp/L-amino acid and CBZ-L-Asp/D-sugar showed strong correlations with the water solubility of either L-amino acids or D-sugars. In contrast. the hydrophobicity of individual compounds did not show any correspondence with T-MB depression. The peak height of X-ray diffractions in the mixture of either CBZ-L-Asp/L-Lys or CBZ-L-Asp/L-Tyr was significantly reduced only when either L-Lys or L-Tyr was soluble in the adjuvant. These results show that the solubilization of a substrate component to an adjuvant contributed to the T-MB depression, which may be caused by the enhanced structural homogeneity of a binary mixture. (C) 2008 Elsevier B.V. All rights reserved.