title: A simulation of oral absorption using classical nucleation theory.
abstract: The purpose of the present study was to investigate the applicability of the classical nucleation theory (CNT) for oral absorption simulation. The CNT was used to simulate the precipitation of low solubility basic compounds in the fasted state simulated intestinal fluid. The infusion-precipitation experiment data reported by Kostewicz et al. [Kostewicz, E.S., Wunderlich, M., Brauns, U., Becker, R., Bock, T., Dressman, J.B., 2004. Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J. Pharm. Pharmacol. 56, 43-51] was used for validation. The surface tension of a drug and a pre-exponential factor were obtained by fitting to the experimental data. The CNT adequately simulated the precipitation characteristics of experimental data such as the increase of the precipitation rate and less sensitivity of maximum concentration by the increase of infusion rate.
authors.affiliation: Global Research & Development, Sandwich Laboratories, Research Formulation, Pfizer Inc., CT13 9NJ, Sandwich, Kent, UK. Kiyohiko.Sugano@pfizer.com
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D011232:Chemical Precipitation; D003198:Computer Simulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000378:metabolism; D008823:Micelles; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013500:Surface Tension
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles; D004364:Pharmaceutical Preparations