Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system.
AAPS PharmSci
; 1(2): E3, 1999.
Article
em En
| MEDLINE
| ID: mdl-11741200
ABSTRACT
The objectives were 1) to design a continuous dissolution/Caco-2 system to predict the dissolution-absorption relationships for fast and slow dissolving formulations of piroxicam, metoprolol tartrate, and ranitidine HCl, and compare the predicted relationships with observed relationships from clinical studies; 2) to estimate the effect of croscarmellose sodium on ranitidine dissolution-absorption relationships; and 3) to estimate the effect of solubilizing agents on piroxicam dissolution-absorption relationships. A continuous dissolution/Caco-2 system was constructed from a dissolution apparatus and a diffusion cell, such that drug dissolution and permeation across a Caco-2 monolayer would occur sequentially and simultaneously. The continuous system generally matched observed dissolution-absorption relationships from clinical studies. For example, the system successfully predicted the slow metoprolol and slow ranitidiine formulations to be permeation-rate-limited. The system predicted the slow piroxicam formulation to be dissolution-rate-limited, and the fast piroxicam formulation to be permeation-rate-limited, in spite of piroxicam's high permeability and low solubility. Additionally, the system indicated croscarmellose sodium enhanced ranitidine permeability and predicted solubilizing agents to not modulate permeability. These results suggest a dissolution/Caco-2 system to be an experimentally based tool that may predict dissolution-absorption relationships from oral solid dosage forms, and hence the relative contributions of dissolution and permeation to oral drug absorption kinetics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ranitidina
/
Piroxicam
/
Metoprolol
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article