In vitro system to evaluate oral absorption of poorly water-soluble drugs: simultaneous analysis on dissolution and permeation of drugs.
OBJECTIVE
The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers.


METHODS
Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose.


RESULTS
Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs.


CONCLUSIONS
With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.
Kataoka
Makoto
M
Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho 45-1, Hirakata, Osaka 573-0101, Japan. makoto@pharm.setsunan.ac.jp
Masaoka
Yoshie
Y
Yamazaki
Yukako
Y
Sakane
Toshiyasu
T
Sezaki
Hitoshi
H
Yamashita
Shinji
S
D000284:Administration, Oral; D000327:Adsorption; D018938:Caco-2 Cells; D006118:Griseofulvin; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011433:Propranolol / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012995:Solubility; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors; D014867:Water / Q000737:chemistry
D004364:Pharmaceutical Preparations; D014867:Water; D012710:Serum Albumin, Bovine; D006118:Griseofulvin; D013656:Taurocholic Acid; D011433:Propranolol