Intestinal Permeation Enhancers

This review addresses the field of improving oral bioavailability through the use of excipients that increase intestinal membrane permeability. The critical issues to consider in evaluating these approaches are 1) the extent of bioavailability enhancement achieved, 2) the influence of formulation and physiological variables, 3) toxicity associated with permeation enhancement, and 4) the mechanism of permeation enhancement. The categories of permeation enhancers discussed are surfactants, fatty acids, medium chain glycerides, steroidal detergents, acyl carnitine and alkanoylcholines, N‐acetylated α‐amino acids and N‐acetylated non‐α‐amino acids, and chitosans and other mucoadhesive polyers. Some of these approaches have been developed to the stage of initial clinical trials. Several seem to have potential to improve oral bioavailabilities of poorly absorbed compounds without causing significant intestinal damage. In addition, the possible use of excipients that inhibit secretory transport is reviewed. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89:429–442, 2000