Beta-cyclodextrin as a suitable solubilizing agent for in situ absorption study of poorly water-soluble drugs.
To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to completely dissolve them in a medium and to avoid precipitation during experiments. This study was undertaken to find an agent possessing a high-solubilizing capacity and exhibiting minimal modulating impact on membrane integrity and absorption systems such as passive diffusion and carrier-mediated permeation. Phenytoin dissolution was compared in the presence of seven solubilizing agents at concentrations of 1, 2, or 5% using a centrifugation method. The capacity to dissolve phenytoin was great in beta-cyclodextrin (beta-CD) and hydroxypropyl beta-cyclodextrin, followed by Tween 80. Those of methanol, dimethyl sulfoxide, dimethyl acetoamide, and polyethylene glycol 400 were much lower than expected. One percent beta-CD did not alter the absorption of fluorescein isothiocyanate-dextran 4,000 or the release of protein and lactate dehydrogenase into in situ loop contents, suggesting that 1% beta-CD had no significant impact on the integrity of the intestinal membrane. One percent beta-CD also did not alter the absorption of caffeine, ceftibuten, or rhodamine 123 from in situ jejunal loops, indicating no interference with passive diffusion and active transports mediated by a peptide transporter and P-glycoprotein. In conclusion, 1% beta-CD is a suitable solubilizing agent for evaluating in situ intestinal absorption of poorly water-soluble compounds.
Oda
Masako
M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Saitoh
Hiroshi
H
Kobayashi
Michiya
M
Aungst
Bruce J
BJ
D000818:Animals; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000493:pharmacokinetics*; D014867:Water / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000493:pharmacokinetics*
D012997:Solvents; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; D014867:Water; C031215:betadex