Solubility of a compound with fasciolicidal activity: evaluation of efficacy in vitro and experimentally on infected sheep with Fasciola hepatica

Compound alpha (Ca) is a benzimidazolic derivate which has shown a high fasciolicidal efficacy when it is given by oral via. Solubilization of Ca would be a suitable alternative to obtain an injectable formulation. The objectives of the present study were to evaluate the solubility of Ca in order to determine the in vitro fasciolicidal efficacy and experimentally on infected ovines. The assays Of Solubility quantified by high-performance liquid chromatography (HPLC), showed that beta-cyclodextrin (beta-CD) and hydroxi-propylbeta-cyclodextrin (HP-beta-CD) solubilized in 0.015% and 1.018% respectively, The solubilization for HP-beta-CD was calculated as 3.95% for 5.8 mg; 10.76% for HP-beta-CD with methanol, 39.048% for proylene-glycol (PG), 100% for glycerol formal (GF), and 100% for combined PG and GF and water in proportions of 3:2:5 and 3:2:4, In vitro evaluation using immature F. hepatica showed that Ca induced 100% efficacy 24 hours after solubilization with either GF or GF combined with PG and water. The efficacy in sheep was 56.4 and 68.4% at 1 and 2 mg/kg respectively; whereas I mg/kg of sulphoxide metabolite induced an efficacy of 73.9%. The HPLC assays performed showed no evidence of the sulphoxide and sulphone metabolites. It is concluded that besides solubility and high in vitro fasciolicidal efficacy, the in vivo results in sheep showed only a moderate efficacy.