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.
ABSTRACT
Objective To study the temporal changes of alveolar epithelial type Ⅱ cells and surfactant pro-tein A in young rats with acute lung injury induced by lipopolysaecharide. Method Totally 110 SD young rats (male:53, female : 57) were randomly divided into ALI and normal control groups (six subgroups in each group).LPS(4 mg/kg) was given intraperitoneally in ALI group. The same amount of normal saline was given in the con-trol groups. Eight rats in each subgroup were sacrificed at 6, 12, 24, 36, 48 and 72 hours after the injection.Lung samples were taken for transmission electron microscope examination. RT-PCR was epmloyed for the mea-surement of SP-A mRNA. Western blot was used for the detection of SP-A in the lung tissue. ANOVA and homo-geneity of variance test were performed by SPSS 12.0. Results The microvilli disappeared at 24 hours after the injection of LPS. The number of lamellar body (LBs) was provisionality increased at 24 hours and 48 hours. The ring-like an'angement of LBs around nucleus and the giant LB with vacuole-like deformity were found as the main characteristics of AEC- Ⅱ in ALI at 48 hours. The number of LBs reduced and broken and residual LB remained at 72 hours. SP-A elevated greatly from 24 to 48 hours (P < 0.01), reached peak at 36 hours (6.94 ± 0.80, P <0.01),reached the lowest level(3.87 ±0.50, P <0.01)at 72 hours. Conclusions The pathological changes of AEC-Ⅱ and SP-A in lung tissue wiht ALI are time-dependent. The typical alterations of AEC- Ⅱ occurs at 48 hours accompanied by the compensatory increase of SP-A. AEC- Ⅱ is seriously injuried with the typical changes of LBs and the diminishing of SP-A in lung tissue.