Structural features, dissolution performance and anthelmintic efficacy of multicomponent solid forms of fenbendazole with maleic and oxalic acids

DOI: 10.1039/D2CE01644C

Authors: Artem Olegovich Surov (G.A. Krestov Institute of Solution Chemistry RAS) , Nikita Vasilev (G.A. Krestov Institute of Solution Chemistry RAS) , Oxana V. Magdysyuk (Diamond Light Source) , German L. Perlovich (G.A. Krestov Institute of Solution Chemistry RAS) , Anastasiya Varlamova (Federal State Budget Scientific Institution) , Ivan Arkhipov (Federal State Budget Scientific Institution) , Irina Odoevskaya (Federal State Budget Scientific Institution)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Crystengcomm

State: Published (Approved)
Published: February 2023
Diamond Proposal Number(s): 26476

Abstract: Two new multicomponent crystalline phases of fenbendazole (FNB), a benzimidazole-based anthelmintic drug, with maleic and oxalic acids have been obtained, and their structural and physicochemical properties carefully investigated. The crystal structures of the solid forms have been determined from powder X-ray diffraction data. The positions of dynamic hydrogen atoms have been further refined via dispersion-corrected density functional theory calculations, which validated the salt nature of the resulting solid forms by demonstrating proton transport from the corresponding acids to the FNB molecule. The in vitro dissolution performance of the solid forms in aqueous media at different pH values, as well as the in vivo anthelmintic efficacy of fenbendazole on the laboratory model of Trichinella spiralis infection in mice have been evaluated and compared to that of the previously reported salt of FNB with p-toluenesulfonic acid. A relationship between the in vitro dissolution characteristics and the in vivo therapeutic action has been revealed and discussed.

Subject Areas: Chemistry, Medicine, Biology and Bio-materials


Instruments: I12-JEEP: Joint Engineering, Environmental and Processing

Added On: 03/02/2023 08:18

Discipline Tags:

Infectious Diseases Disease in the Developing World Health & Wellbeing Biochemistry Information & Communication Technologies Chemistry Organic Chemistry Drug Discovery Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction X-ray Powder Diffraction