New antifungal compound: Solubility thermodynamics and partitioning processes in biologically relevant solvents.

A novel potential antifungal compound of 1,2,4-triazole class - ((5Z)-5-[(4-chlorophenyl)methylidene]-3-(2-{4-[2-(2,5-difluorophenyl)-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]piperazin-1-yl}-2-oxoethyl)-1,3-thiazolidine-2,4-dione) (L-173) - has been synthesized and characterized. Some pharmacologically relevant physicochemical properties have been determined for the first time. Solubility in buffer solutions (pH 1.2, 2.0, and 7.4), ethanol, hexane, and octanol was measured by the shake flask method in the temperature range of 293.15–313.15 K. L-173 was shown to be poor soluble in buffer solutions and hexane, at the same time, better solubility in alcohols was revealed. The Van't Hoff and Apelblat equations gave good correlations when used for modeling the experimental solubility results. The solubility evaluation in different solvents with the help of Hansen solubility parameters and the atomic group contribution approach of Hoftyzer and Van Krevelen showed the consistency with the experimental data and revealed good potential adsorption of the investigated drug. The thermodynamic parameters of solubility and transfer processes were calculated and discussed in view of solute-solvent interactions. The ∆logD parameter determined from the distribution experiment clearly demonstrated the preference of lipophilic delivery pathways for L-173 in the biologic media. • Solubility of antifungal compound in buffers, hexane, and alcohols was assessed. • Good adsorption in the GIT by Hansen solubility parameters was proposed. • Analysis of transfer solubility thermodynamics approved the Hansen results. • Parameter ∆logD showed the preference of lipophilic delivery pathways for the drug. [ABSTRACT FROM AUTHOR]