In Vitro Dissolution/Permeation System to Predict the Oral Absorption of Poorly Water-Soluble Drugs: Effect of Food and Dose Strength on It

• Published in: Biological & pharmaceutical bulletin 2011/03/01, Vol.34(3), pp.401-407
• Main Authors: Kataoka, Makoto, Itsubata, Sachi, Masaoka, Yoshie, Sakuma, Shinji, Yamashita, Shinji
• Format: Article
• Language: English
• Subjects: absorption; Administration, Oral; Caco-2 Cells; Cilostazol; dissolution; Dose-Response Relationship, Drug; Fasting; food effect; Food-Drug Interactions; Humans; Intestinal Absorption; Permeability; Pharmaceutical Preparations - analysis; poorly water-soluble drug; Postprandial Period; Solubility; Technology, Pharmaceutical - methods; Tetrazoles - pharmacokinetics; Water
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.34.401

The aim of the present work was to confirm the usefulness of the dissolution/permeation system (D/P system) in the estimation of human oral absorption of poorly water-soluble drugs. The D/P system, which can simultaneously evaluate drug absorption processes, dissolution and permeation, can predict the oral absorption of poorly water-soluble drugs in fasted and fed humans, with a correlation between in vivo oral absorption (% of absorbed) and in vitro permeated amount (% of dose/2 h) in the D/P system. The oral absorption (fraction of absorbed dose, %) of poorly water-soluble drugs in the fasted and fed states was predicted using the D/P system. The effect of food on the oral absorption of various drugs estimated by the D/P system significantly correlated with clinical data (correlation coefficient: r2=0.924). Moreover, the proportion of oral absorption of cilostazol was predicted to decrease with an increase in its dose strength, which significantly correlated with in vivo human absorption. Consequently, the D/P system was demonstrated to be a useful in vitro system for prediction of the oral absorption of poorly water-soluble drugs.