Critical evaluation of permeation enhancers for oral mucosal drug delivery

Drug delivery via oral mucosa is an alternative method of systemic administration for various classes of therapeutic agents. Among the oral mucosae, buccal and sublingual mucosae are the primary focus for drug delivery. Buccal delivery offers a clear advantage over the peroral route by avoidance of intestinal and hepatic first-pass metabolism. However, despite offering the possibility of improved systemic drug delivery, buccal administration has been utilized for relatively few pharmaceutical products so far. One of the major limitations associated with buccal delivery is low permeation of therapeutic agents across the mucosa. Various substances have been explored as permeation enhancers to increase the flux/absorption of drugs through the mucosa, but irritation, membrane damage, and toxicity are always associated with them and limit their use. A clinically accepted permeation enhancer must increase membrane permeability without causing toxicity and permanent membrane damage. To date, the information available on oral mucosal permeation enhancement is much less than transdermal enhancement, though oral mucosa is more resistant to damage than other mucosal membranes. This article reviews the various categories of permeation enhancers for oral mucosal drug delivery, their mechanism of action, their usefulness, and the limitations associated with their use.To optimize the concentration of enhancer to limit its toxicity while facilitating an enhancing effect reproducibly will be a big challenge for future developments. Advances in permeability modulation and formulation with appropriate enhancers can provide for effective and feasible buccal drug delivery for many drugs, which otherwise have to be injected or ingested with water.