Development and Pharmacokinetic Evaluation of Two Parenteral Formulations of Albendazole Using Prodrug and Cosolvent Approaches
Por:
Becerril-Vega, Jose, Hernandez-Campos, Alicia, Gonzalez-Hernandez, Iliana, Flores-Ramos, Miguel, Castillo, Rafael, Leyva-Gomez, Gerardo, Mayet-Cruz, Lourdes, Jung-Cook, Helgi
Publicada:
27 jul 2023
Resumen:
Albendazole is a broad-spectrum anthelmintic drug used for parasitic
infections. In addition, due to its mechanism of action, it has been
studied as an anticancer agent. However, poor and highly variable
bioavailability are limiting factors for its use in systemic illnesses.
The present study aimed to develop two parenteral formulations of
albendazole and to compare its pharmacokinetic profile with the
conventional oral administration. Parenteral formulations were developed
using two different approaches: a phosphonooxymethylated prodrug and
cosolvents. For the albendazole prodrug, once synthetized, its
solubility and hydrolysis with alkaline phosphatase were evaluated. A
factorial design of experiments was used for the cosolvent formulation.
Stability and hemolytic activity were assessed. A pharmacokinetic study
was performed on New Zealand rabbits. Both formulations were
administered intravenously, and the prodrug was also administered
intramuscularly. Results were compared with those obtained after the
oral administration of albendazole. A 20,000-fold and 6000-fold increase
in albendazole solubility was found with the prodrug and cosolvent
formulations, respectively. Both parenteral formulations displayed
higher albendazole plasma concentrations for the first 2 h compared with
oral administration, even when the oral dose was doubled. The absolute
bioavailability of oral albendazole was 15.5% while for the
intramuscular administration of the prodrug was 102.6%. Both parenteral
formulations showed a significant decrease in the formation of
albendazole sulfoxide (ANOVA p<0.05) and allowed greater exposure to
albendazole. Albendazole cosolvent parenteral formulation could be a
promising option in systemic illnesses considering its ease of
preparation and superb pharmacokinetic performance.
Filiaciones:
Becerril-Vega, Jose:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
Hernandez-Campos, Alicia:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
Gonzalez-Hernandez, Iliana:
Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico
Inst Nacl Neurol & Neurocirugia Manuel Velasco Sua, Lab Neuropsicofarmacol, Mexico City, Mexico
Flores-Ramos, Miguel:
Escuela Nacional de Estudios Superiores, Unidad Mérida, Universidad Nacional Autónoma de México, Yucatán, Mexico
Univ Nacl Autonoma Mexico, Escuela Nacl Estudios Super, Unidad Merida, Merida, Yucatan, Mexico
Castillo, Rafael:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
Leyva-Gomez, Gerardo:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
Mayet-Cruz, Lourdes:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
Jung-Cook, Helgi:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, Mexico
hybrid, Hybrid Gold
|