Development of a new benazepril hydrochloride chewable tablet and evaluation of its bioequivalence for treatment of heart failure in dogs

Abstract

The aim of the study was to develop a new chewable benazepril hydrochloride(BH) tablet, investigate its physical properties, and evaluate its bioequivalence with the branded formulation (Fortekor). A corrective agent was included in the formula to improve its palatability and convenience for administration to dogs. The tablet remained stable in light, heat, and humidity tests, and its physical properties such as hardness, uniformity of content, and dissolution rate were highly consistent with the technical standards. After single and repeated administrations to eight beagles and single dose to 14 mongrel dogs (0.5 mg/kg p.o.), plasma BH and its active metabolite, benazeprilat (BZ), were detected. There was no significant difference in the major pharmacokinetic parameters (Cmax , Tmax, and AUC₀₋₂₄) between the two formulations. The 90% confidence intervals calculated for the ratios of area under the time-concentration curve (AUC₀₋₂₄) were 92.4-116.3% for BH and 89.9-102.3% for BZ, within the accepted range for bioequivalence of 80-125%. The results showed our new chewable tablet is bioequivalent to the commercial product and suitable for addition to the benazepril product family for the treatment of heart failure in dogs.