title: Perspective on improving passive human intestinal absorption.
abstract: Methods such as pH adjustment, cosolvency, complexation, and micellization are routinely used to increase the concentration of dissolved drug in the gastrointestinal (GI) lumen over that of a saturated solution. However, these solubilizing agents also reduce the membrane-water distribution coefficient so that the membrane transport rate is not changed. Also, dilution of a formulation upon administration results in: (1) a pH change toward that of the GI fluid, (2) an exponential decrease in cosolvency, and (3) disassociation of complexes and the disintegration of micelles. As a result, these solubilizing agents cannot be expected to produce any increase in membrane transport-limited drug absorption over that of a suspension of unformulated drug.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA. yalkowsky@pharmacy.arizona.edu
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Yalkowsky
mesh_terms: D000284:Administration, Oral; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects*; D008823:Micelles; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D005079:Excipients; D008823:Micelles; D004364:Pharmaceutical Preparations; D012997:Solvents