A Water-Soluble Fenbendazole (FBZ) Formulation for Treating Pinworm Infections in Laboratory Animals

Jang-Ha      Ryu; James      Diakur; Sandra   E.   Kelly; James   C.   Russell; Leonard   I.   Wiebe

doi:10.2174/2210303111303030001

Abstract

Fenbendazole (FBZ) is an oral veterinary medication given daily for 3 consecutive days to treat oxyurid (Syphacia, pinworm) infections (oxyuriasis) and other parasites. A species-dependent oral dose of 5-20 mg/kg/day completely eliminates the parasite. FBZ is usually administered in food rations, but costs associated with FBZ-treated food are high. The low water solubility of FBZ (<0.1 g/L) mitigates against its delivery via drinking water. This manuscript describes the formulation of FBZ as a hydroxypropyl-β-cyclodextrin (HPCyD) inclusion complex (FBZ-HPCyD). A method to control the bulk density of the fluffy inclusion complex powder for tableting, and a method to color-code the product when added to drinking water using a US FDA acceptable food dye are reported. FBZ-HPCyD was formulated by sequentially dissolving HPCyD in distilled water, adding FBZ and then sonicating and stirring this mixture for 5 days at room temperature. The solution was filtered (0.45 μm filter) to remove undissolved FBZ and then subjected to multistep freezedrying. The resulting dried powder was mechanically pulverized to achieve the desired particle size. The formulated powder FBZ-HPCyD was assayed for FBZ. FBZ-HPCyD and FDC red #40 color were mixed, dry granulated and directly compressed using a single-punch press. The 450 mg color-coded tablets, administered to Syphacia obvelata infected rats via their drinking water supply, effectively eradicated infections over a four day period when six tablets were used per 500 mL water bottle.

Keywords: Cyclodextrins, drinking water, fenbendazole, hydroxypropyl-β-cyclodextrin, pinworms, water-soluble formulation.