Determination of Equilibrium Solubility of Albendazole and Its Apparent Oil-Water Partition Coefficient / 中国药房

ABSTRACT

OBJECTIVE:To determine the equilibrium solubility of albendazole(ABZ)and its apparent oil-water partition coef-ficient. METHODS:The equilibrium solubility of ABZ in various solutions was determined at 37 ℃ by HPLC and saturation solu-bility method,including water,7 kinds of common organic solvents with different polarities(methanol,ethanol,etc.),organic ac-id(oleic acid,glacial acetic acid,lactic acid,formic acid),hydrochloric acid of pH 1.2,phosphate buffer solution(PBS)of dif-ferent pHs(2.0-7.8)and 6 kinds of common surfactants with mass concentrations of 10,50 and 100 mg/ml(polysorbate 80,polox-amer,etc.). The apparent oil-water partition coefficient(P)was calculated with the concentration ratio of ABZ in oil phase(N-oc-tyl alcohol)and water phase(water and PBS of different pHs)after partition equilibrium. RESULTS:The equilibrium solubility of ABZ reached(0.26±0.02)μg/ml in water,with the lgP of 3.66±0.01. The equilibrium solubility of ABZ in common organic sol-vents and organic acids was higher than in water. The higher the polarity of the organic solvent was and the weaker of organic acid was,the weaker of its ability to solubilize ABZ would be. The equilibrium solubility of ABZ was higher in the medium of pH 1.2-2.5 than in that of pH 5.0-7.8. The ability of the surfactant to solubilize ABZ was related to its type,and the higher of the mass concentration of the surfactant was,the stronger of its ability to solubilize ABZ became. lgP was less than 1.6 at pH 1.2-2.0 and changed little at pH 5.0-7.8 [(3.71 ± 0.26)-(3.68 ± 0.26)]. CONCLUSIONS:ABZ is insoluble in water. Its equilibrium solubility demonstrates a negative correlation with the polarity of the organic solvent and a positive correlation with the acidity of the organic acid and with the mass concentration of the surfactant. It has higher water solubility and lower lipid solubility in a strong acidic en-vironment,and higher lipid solubility and weaker water solubility in weak acidic,weak basic and neutral environments.