Improved pharmacokinetics of AMG 517 through co-crystallization. Part 1: comparison of two acids with corresponding amide co-crystals.
J Pharm Sci
; 99(9): 3769-78, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20665842
ABSTRACT
The dissolution and pharmacokinetics (PK) of two carboxylic acid co-crystals (cinnamic acid and benzoic acid) with the corresponding amide co-crystals (cinnamamide and benzamide) of AMG 517 were investigated. Powder and intrinsic dissolution studies were performed in fasted simulated intestinal fluid (FaSIF). Suspension formulations in 1% polyvinylpyrrolidone K25 in water were administered orally at 100 mg/kg to rats. The four co-crystals were found to have faster intrinsic and powder dissolution rates in FaSIF than the free base. This correlated with a 2.4- to 7.1-fold increase in the area under the concentration-time curve in rat PK investigations. When contrasting the acid to its corresponding amide co-crystal, cinnamamide shows improvement over cinnamic acid, while benzamide and benzoic acid perform similarly.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Benzotiazóis
/
Canais de Cátion TRPV
Limite:
Animals
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos