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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3047–3050, 2012