Fosfatriclaben, a prodrug of triclabendazole: Preparation, stability, and fasciolicidal activity of three new intramuscular formulations.

Abstract

In this study, we present the preparation, stability, and in vivo fasciolicidal activity of three new intramuscular formulations in sheep of a prodrug based on triclabendazole, named fosfatriclaben. The new formulations were ready-to-use aqueous solutions with volumes recommended for intramuscular administration in sheep. The use of poloxamers (P-407 and P-188) and polysorbates (PS-20 and PS-80) in the new formulations improved the aqueous solubility of fosfatriclaben by 8-fold at pH 7.4. High-performance liquid chromatography with UV detection was used to evaluate the stability of fosfatriclaben in the three formulations. High recovery (> 90%) of fosfatriclaben was found for all formulations after exposure at 57 ± 2 °C for 50 h. The three intramuscular formulations showed high fasciolicidal activity at a dose of 6 mg/kg, which was equivalent to the triclabendazole content. The fasciolicidal activity of fosfatriclaben was similar to commercial oral (Fasimec®) and intramuscular (Endovet®) triclabendazole formulations at a dose of 12 mg/kg. In the in vivo experiments, all formulations administered intramuscularly reduced egg excretion by 100%, and formulations F1, F2, and F3 presented fasciolicidal activities of 100%, 100%, and 99.6%, respectively.