Development of novel benznidazole formulations: physicochemical characterization and in vivo evaluation on parasitemia reduction in Chagas disease.
Int J Pharm
; 472(1-2): 110-7, 2014 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-24928135
ABSTRACT
This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZL-HPC solid dispersion at a 13 ratio (w/w) (SD-13 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged release (24% at 30 min for SD-13 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-13 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZL-HPC systems enhance the bioavailability of the drug.
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Bases de datos:
MEDLINE
Asunto principal:
Tripanocidas
/
Portadores de Fármacos
/
Enfermedad de Chagas
/
Parasitemia
/
Nitroimidazoles
Límite:
Animals
Idioma:
En
Revista:
Int J Pharm
Año:
2014
Tipo del documento:
Article
País de afiliación:
España