Effects of Ingested Water Volume on Oral Absorption of Fenofibrate, a BCS Class II Drug, from Micronized and Amorphous Solid Dispersion Formulations in Rats.
Biol Pharm Bull
; 45(10): 1452-1457, 2022.
Article
em En
| MEDLINE
| ID: mdl-36184502
ABSTRACT
In this study, we investigated the effects of ingested water volume on the oral absorption of fenofibrate (FEN) with several formulations to confirm the applicability of rats for oral formulation screening. Oral absorption of suspended crystalline FEN was significantly improved by increasing ingested water volume (from 0.5 to 2 mL). FEN absorption improvement by particle size reduction and the linearity in oral absorption by dose escalation suggested that the rate-limiting step of FEN absorption in rats was the dissolution rate, consistent with that in humans. When FEN, as an amorphous solid dispersion (ASD) formulation, was suspended in water followed by immediate administration, oral FEN absorption was significantly higher than when administered in crystalline form and was not influenced by the differences in ingested water volume. Oral absorption of FEN from encapsulated ASD formulation in 1 or 2 mL of water was comparable with that of the suspension form. However, 0.5 mL of water significantly reduced the oral absorption of the solid ASD FEN formulation. These results indicate that to improve the oral absorption of poorly water-soluble drugs when performing a preclinical study with rats, 1 mL of water is the minimum preferable ingested volume to evaluate in vivo formulation performance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenofibrato
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biol Pharm Bull
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de publicação:
JAPAN
/
JAPON
/
JAPÃO
/
JP