Perspective on Improving Passive Human Intestinal Absorption

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 9; pp. 3047 - 3050
• Main Author: Yalkowsky, Samuel H.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: absorption; Administration, Oral; bioavailability; Biological and medical sciences; Biological Transport; Chemistry, Pharmaceutical; complexation; Drug Carriers; Excipients - chemistry; Excipients - pharmacology; General pharmacology; Humans; Hydrogen-Ion Concentration; intestinal absorption; Intestinal Absorption - drug effects; Medical sciences; micelle; Micelles; Models, Biological; Models, Chemical; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility; Solvents - chemistry; Solvents - pharmacology; Technology, Pharmaceutical - methods; pH; micelle; intestinal absorption; complexation; absorption; bioavailability; Human; Complexation; Perspective; Absorption; Pharmaceutical technology; Gut; Micelle; Bioavailability; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23093

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