title: The Use of Bile Salt Micelles for the Prediction of Human Intestinal Absorption.
abstract: Human intestinal absorption (HIA) will dictate biopharmaceutical performance through its influence on absorption, distribution, metabolism, and elimination and can vary significantly depending upon the nature of the compound under consideration. In this study, an in vitro assay method is proposed for the prediction of HIA through the measurement of drug solubility in an aqueous phase containing micellar bile salt, namely sodium deoxycholate. A series of twenty compounds, displaying a range of physicochemical properties and known HIA values, were analyzed using UV spectroscopy to determine a solubilization ratio for each compound. A micelle/water partition coefficient (Kxm/a) was calculated and then used to develop an equation through simple linear regression; logit HIA = -0.919 + 0.4618 logKxm/a(R2= 0.85). From this equation, a value for % HIA was determined which compared well with literature. Furthermore, 4 additional drugs were then analyzed using the developed equation and found to match well with literature, confirming the suitability of the method. Using a simple, economic, and robust UV bile salt assay allows prediction of HIA and avoids many of the disadvantages of other techniques, such as animal-based methods.
authors: School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. Electronic address: l.waters@hud.ac.uk.
authors: Laura J
authors: LJ
authors: Waters
authors: School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
authors: Dina S
authors: DS
authors: Shokry
authors: School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
authors: Gareth M B
authors: GMB
authors: Parkes
authors: Faculty of Engineering and Science, Medway Centre for Formulation Science, University of Greenwich, Chatham, Kent ME4 4TB, UK.
authors: John C
authors: JC
authors: Mitchell
mesh_terms: D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D005544:Forecasting; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008823:Micelles
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles
keywords: HIA; UV; bile salts; human intestinal absorption; solubilization