Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Inhibitory effect of fenbendazole on proliferation of human chronic myelogenous leukemia K562 cells / 中国病理生理杂志

AIM:To investigate the effect of fenbendazole (FBZ) on the proliferation of human chronic myelogenous leukemia (CML) cell line K562.METHODS:The CCK-8 assay was used to detect the effect of FBZ on viability of the K562 cells and normal peripheral blood mononuclear cells (PBMC).The cell growth was measured by the method of Trypan blue exclusion.The cell cycle was analyzed by flow cytometry.The cell cycle-related proteins were detected by Western blot.RESULTS:The growth of K562 was significantly inhibited by FBZ.However, it elicited little cytotoxic effect on PBMC.Furthermore, FBZ induced G2/M phase arrest and mitotic catastrophe in the K562 cells based on the changes of nuclear morphology, DNA content, mitotic marker analysis and the number of polykaryocytes.CONCLUSION:Fenbendazole significantly inhibits the proliferation of K562 cells and induces cell cycle arrest at G2/M phase by the regulation of cell cycle-related proteins.

Determination of Fenbendazole and Praziquantel in Compound Fenbendazole Tablets by HPLC / 中国药师

Objective:To develop an HPLC method for the determination of fenbendazole and praziquantel in compound fenbendazole tablets. Methods:An InertSustain? C18 column(250 mm × 4. 6 mm,5 μm)was used. The mobile phase was acetonitrile-phosphate buffer(pH = 3)(48 ∶52)and the flow rate was 1. 0 ml·min-1 . The detection wavelength was 214 nm,the column temperature was 30 ℃ and the sample size was 10 μl. Results:The linear range of fenbendazole and praziquantel was 4. 545- 63. 630 μg·ml -1(r = 0. 999 9)and 0. 225- 3. 150 μg·ml-1(r = 0. 999 9),respectively. The average recovery was 101. 09%(RSD = 0. 28% ,n = 9)and 99. 47%(RSD = 0. 78% ,n = 9),respectively. Conclusion:The method is simple,fast, accurate and applicable in the determination of fenbendazole and praziquantel in compound fenbendazole tablets.

Pharmacokinetics of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, and administered orally to mice at a single dose / 中国药学杂志

OBJECTIVE: To determine the pharmacokinetics of three benzimidazoles (albendazole, fenbendazole and fluben-dazole) suspended in three different media [oleic acid, soybean oil or 1% tragacanth (served as control)] in mice, and observe the correlation of those pharmacokinetic parameters with the solubilities of the three benzimidazoles in corresponding medium. METHODS: Albendazole, fenbendazole and flubendazole suspened in oleic acid, soybean oil or 1% tragacanth were prepared by ball grinding mill. Groups of 45-54 mice were administered orally with one of aforementioned benzimidazole suspensions at a single dose of 100 mg · kg-1 (albendazole) or 50 mg · kg-1 (fenbendazole and flubendazole). Subgroups with 5-6 mice in each group were bled at varying intervals within 24 h. Plasma was then separated from heparin-anticoagulated blood, and evaluated for the presence of the drug by high performance liquid chromatography (HPLC). Pharmacokinetic parameters of each drug were calculated using DAS (Drug AnaLyze System). RESULTS: After oral administration of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, the pharmacokinetic parameters of each drug were described as follows: albendazole, the MRT (average retention time) were (3.91 ± 0.29), (3.70 ± 0.09) and (1.59 ± 0.14) h, ρmax (maximum concentration) were (0.66 ± 0.08), (0.29 ± 0.05) and (0.34 ± 0.09) mg · L-1, AUG (area under the concentration-time curve) were (3.19 ± 0.40), (1.25 ± 0.09) and (0.50 ± 0.05) mg · L · h-1, F (relative bioavailability, the AUC compared with that of 1% tragacanth group) were 6.38 and 2.50; fenbendazole, the MRT were (5.72 ± 0.14), (4.83 ± 0.38) and (3.85 ± 0.25) h, ρmax were(0.70 ± 0.11), (0.20 ± 0.05) and (0.12 ± 0.03) mg · L-1, AUC were (5.02 ± 0.73), (1. 08 ± 0.21) and (0.52 ± 0.07) mg · h · L-1, F were 9.65 and 2.08; flubendazole, the MRT were (5.71 ± 0.37), (4.59 ± 0.39) and (3.34 ± 0.20) h, ρmax were (0.93 ± 0.14), (0.58 ± 0.09) and (0.41 ± 0.09) mg · L-1, AUC were (6.90 ± 0.73), (3.33 ± 0.39) and (1. 94 ± 0.55) mg · L · h-1, F were 3.57 and 1.72. CONCLUSION: After oral administration to mice, the major pharmacokinetic parameters of the three benzimidazoles suspended in oleic acid and soybean oil show significant improvement compared to those of the same drugs suspended in 1% tragacanth, which manifest as prolongation of MRT, and increase of ρmax, AUC as well as F. The solubilities of the three benzimidazoles in three different media were on the whole positive correlative to their MRT, ρmax, AUC and F in mice.

Hemogram of buffaloes (bubalus bubalis) wormed and nonwormed by helminthes

The gastrointestinal parasitoses of domestic animals have a great impact on the hematological status but nonethelessresearch on this subject concerning buffaloes is rare. Thus, the blood profile of buffalo calves naturally infected by parasitesfrom the seventh to the 300th day of life. Animals were distributed in three experimental groups treated with ivermectin,fenbendazole, and placebo, respectively. Changes of hematological parameters were related to the presence of adultgastrointestinal nematodes, which were diagnosed and identified by the presence of eggs in the feces of wormed animals ascompared to those medicated.