Prediction of oral absorption of griseofulvin, a BCS class II drug, based on GITA model: utilization of a more suitable medium for in-vitro dissolution study.
The in-vivo absorbability of drugs categorized into the biopharmaceutics classification system (BCS) class II is very difficult to be predicted because of the large variability in the absorption and/or dissolution kinetics and the lack of an adequate in-vitro system for evaluating the dissolution behavior. We tried to predict the in-vivo absorption kinetics of griseofulvin, categorized into BCS class II, orally administrated as powders into rats, based on Gastrointestinal-Transit-Absorption model (GITA model), consisting of the absorption, dissolution and GI-transit processes. Using the dissolution rate constants (k(dis)) of griseofulvin obtained with JP 1st solution, JP 2nd solution, FaSSIF, FeSSIF and modified SIBLM as a medium, simulation lines were not able to describe the observed mean plasma profile at all. On the other hand, a calculated line provided by employing k(dis) obtained with MREVID 2 (medium reflecting in-vivo dissolution 2), a new medium, was in better agreement with the observed mean plasma profile than existing media, indicating that the utilization of adequate k(dis) value made it possible to predict the in-vivo absorption kinetics of drugs classified into BCS class II based on GITA model and that MREVID 2 could be a useful medium for describing the in-vivo dissolution kinetics.
Fujioka
Yoshitsugu
Y
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Kadono
Keitaro
K
Fujie
Yasuko
Y
Metsugi
Yukiko
Y
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000284:Administration, Oral; D000818:Animals; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D006118:Griseofulvin / Q000008:administration & dosage / Q000145:classification* / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D008956:Models, Chemical; D011208:Powders; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D011208:Powders; D006118:Griseofulvin