Capric Acid Absorption in the Presence of Hydroxypropyl-β-Cyclodextrin in the Rat Ileum using the In Situ Single-Pass Perfusion Technique

ABSTRACTThe purpose of the present study was to gain quantitative mechanistic insight into the role cyclodextrin carriers may play in the intestinal absorption of highly lipophilic molecules. The physical model approach was employed to investigate capric acid absorption in the rat ileum using the in situ single-pass method with 2-hydroxypropyl-β-cyclodextrin (HPB) present in the perfusate. Two physical models were examined: the flat surface model in which the intestinal wall was treated as a hollow, smooth, circular cylinder, and the villus model in which the intestinal surface allowed for the presence of villi. Capric acid absorption was found to be essentially 100% aqueous boundary layer controlled at low HPB concentrations and increasingly membrane controlled at the higher HPB concentrations. Theoretical calculations based on the experimental data and model parameters were found to be consistent with: at low HPB concentrations, capric acid was mainly absorbed at the villus tips and there was very little capric acid penetration into the intervillus space; in contrast, at 50 mM HPB, there was considerable capric acid penetration into the intervillus space, this corresponding to around a 4.5-fold increase in the accessible area for absorption when compared with 0 mM HPB. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2832–2844, 2015