Solid Dispersions of Fenbendazole with Polymers and Succinic Acid Obtained via Methods of Mechanochemistry: Their Chemical Stability and Anthelmintic Efficiency

Abstract

The substance fenbendazole is included in the composition of many anthelmintic drugs, in which the “chemical stability” parameter is one of the main characteristics when obtaining permission for the use of drugs in veterinary practice. Fenbendazole is characterized by low solubility in water and therefore the content of the substance is overestimated in its preparations, which increases the cost of the drug as well as the safety risks of pharmacotherapy. The possibilities of mechanochemical modification of fenbendazole were evaluated in order to improve the solubility index. During the mechanical processing treatment of the substance in the presence of polymeric substances, solid dispersions are formed, which have increased solubility and high anthelmintic activity. The inclusion in these dispersions of the third component, which is succinic acid, did not significantly change the solubility of fenbendazole. In all these dispersions, the substance remained unchanged both during the preparation of its solid dispersions and during their storage. When fenbendazole is modified in an organic solvent medium, the substance is partially converted into oxfendazole, which is one of its metabolites. The chemical stability of fenbendazole was confirmed via HPLC/MS and NMR spectroscopy. The anthelmintic activity of these compositions was evaluated and it was found that they have a high nematicidal activity.

Keywords

• fenbendazole
• polymer substances
• mechanochemistry
• solid dispersions
• chemical stability
• anthelmintic activity