The effect of different polymers on the solubility, permeability and distribution of poor soluble 1,2,4-thiadiazole derivative

Solubility and permeability are the main parameters determining the bioavailability of drugs. In this study the increased solubility of novel 1,2,4-thiadiazole derivative (TDZ) proposed for the prevention and treatment of Alzheimer's disease was achieved in the solutions of polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and pluronic F127 (F127). It was found that solubilizing power of polymers follows the order F127 > PVP > PEG. The mechanism of TDZ solubilization was proposed on the basis of 1H NMR and UV-spectroscopy studies. It was suggested that PEG enhances the TDZ solubility by acting mainly as cosolvent, whereas PVP can be considered as cosolvent and complexing agent. In case of F127, the insertion of TDZ into micelles was detected. The solubilization capacity of pluronic was quantified in terms of average number of TDZ and F127 per micelle and binding constant. In order to reveal the effect of polymers on the TDZ membrane permeability, the distribution coefficients in the 1-octanol/buffer system and permeability coefficients through the novel Permeapad™ barrier were determined. The solubility-permeability and solubility-distribution relationships were discussed.