Solid Forms of The New Antitrypanosomal 1-(4-Acetamide-Benzenesulfonyl)-Benzimidazole: Preparation and Physicochemical Characterization.

This study aimed to investigate the polymorphism of 1-(4-acetamide-benzenesulfonyl)-benzimidazole (PABZI), a newly developed compound with significant activity against Trypanosoma cruzi, the parasite which causes American trypanosomiasis (Chagas disease). Three different crystalline forms of PABZI [a solvent-free form (form I), three isostructural solvates (from isopropanol; acetonitrile-dichloromethane, and methanol-benzene) and a non-isostructural solvate from methanol] were isolated and characterized. The crystal structure of form I was resolved at 173 K and 300 K by single crystal X-ray diffraction. Physicochemical properties, including solubility, dissolution rate, wettability, and solid-state stability were assessed for the two most viable solid forms of PABZI, viz. form I and the isopropanol solvate (PABZI-isoOH). Form I exhibited a higher solubility and dissolution rate, and superior stability towards moisture (40 °C/75 % relative humidity) and UV-Visible light than PABZI-isoOH. Based on the solid-state stability results, form I was selected over PABZI-isoOH for further preclinical studies.

Effect of cyclodextrins on the reactivity of fenitrothion.

The hydrolysis reaction of fenitrothion was studied in water containing 2% dioxane and in the presence of native cyclodextrins (α-, ß- and γ-CD) and two commercially available modified derivatives, namely, permethylated ß- and α-cyclodextrin (TRIMEB and TRIMEA, respectively). The kinetics of the reaction in the presence of TRIMEA could not be measured because the complex formed is insoluble and precipitated even at low concentration. On the other hand, the reaction is only weakly affected by the presence of α-CD. The hydrolysis reaction is inhibited by all the other cyclodextrins. From the kinetic data the association equilibrium constants for the formation of the 1:1 inclusion complexes were determined as 417, 511 and 99M(-1) for ß-CD, TRIMEB and γ-CD, respectively. Despite the differences in the association constants for ß- and γ-CD, the observed inhibition effect is about the same and this is due to the fact that the rate of hydrolysis in the cavity of γ-CD is smaller than that in the cavity of ß-CD. The strongest inhibitor is TRIMEB and this result is consistent with the known structure of the complex in the solid state.