Thiazolidine-2,4-dione derivative in 2-hydroxypropyl-β-cyclodextrin solutions: Complexation/solubilization, distribution and permeability

Abstract

Since a majority of drug substances are poor soluble in aqueous solutions, suitable drug formulations are often used. Among others, the cyclodextrin-based pharmaceutical products have been shown to be successful for a large variety of drugs. In this study, based on the results of previous investigation on the solubility of novel potential antifungal compound (5Z)-3-(3-(4-acetylpiperazin-1-yl)-2-hydroxypropyl)-5-(4-chlorobenzylidene)thiazolidine-2,4-dione (TZD) in pure solvents, the overall physicochemical study of solubility, distribution and membrane permeability of this compound in the presence of 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) was carried out in buffer solutions at pH 2.0 and pH 7.4. In order to estimate the driving forces of the solubilization, complexation and partition processes representing a particular importance for the prediction of drug behavior in biological media, the solubility and distribution experiments were performed in the range of 298.15–313.15 K. The distribution behavior of TZD in the 1-octanol/buffer and n-hexane buffer systems at pH 2.0 and pH 7.4 in the presence of 0.01 M 2HP-β-CD was studied. In order to elucidate a role of hydrogen bonding, the ∆logD parameter coming from the difference between the distribution coefficient in octanol/water and hexane/water systems was evaluated. The permeability coefficients through the Permeapad™ barrier from buffer pH 2.0 and pH 7.4 to buffer pH 7.4 have been determined in the presence of 2HP-β-CD in order to evaluate the permeation of TZD across the stomach and intestine membranes, respectively.