Improving the in vitro dissolution rate and pharmacokinetic performance of fenbendazole in sheep using drug nanocrystals

IBARRA, MANUEL; MUNGUÍA, BEATRIZ; ÁLVAREZ, LUIS IGNACIO; MELIAN, MARÍA ELISA; PAREDES, ALEJANDRO J.; PALMA, SANTIAGO; CEBALLOS, LAURA; FACCIO, RICARDO; DOMÍNGUEZ, LAURA

RESEARCH IN VETERINARY SCIENCE

ELSEVIER SCI LTD

Año: 2022 vol. 142 p. 110 - 116

0034-5288

Benzimidazole methylcarbamate anthelmintics, including fenbendazole (FBZ), have only limited water solubility and small differences in drug solubility may have a major influence on their absorption, pharmacokinetic behavior and anthelmintic efficacy. To improve FBZ water solubility and dissolution rate, novel self-dispersible nanocrystals (SDNCs) of FBZ were recently described. In this work, the pharmacokinetic behavior of the SDNCs of FBZ and Poloxamer 188 was compared against a physical mixture (PM) of its components. The experiment was conducted following a crossover design with two different experimental phases. In phase I, sheep were treated with the SDNC (n = 3) or the PM (n = 3) formulations by the intraruminal route at the same dose rate (5 mg/kg). The treatment groups were reversed after a 7-days washout period. A non-compartmental analysis of the concentration in plasma versus time results showed that the calculated Cmax and AUC0-T were significantly higher (p