Drug permeation enhancement via buccal route: possibilities and limitations

Over the last decade, there has been a particular interest in delivering dr ugs, especially peptides and proteins via the buccal route. It provides dir ect entry into the systemic circulation thus avoiding the hepatic first-pas s effect and degradation in the gastrointestinal tract, ease of administrat ion, and the ability to terminate delivery when required. However membrane permeation can be a limiting factor for many drugs administered via the buc cal route, and the epithelium that lines the oral mucosa is a very effectiv e barrier to the absorption of drugs. In order to deliver broader classes o f drugs across the buccal mucosa, reversible methods of reducing the barrie r potential of this tissue must be employed. This requisite has fostered th e study of penetration enhancers that will safely alter the permeability re strictions of the buccal mucosa, It has been shown that buccal penetration can be improved by using various classes of transmucosal and transdermal pe netration enhancers such as bile salts, surfactants, fatty acids and deriva tives, chelators, cyclodextrins and chitosan. Among these chemicals used fo r the drug permeation enhancement, bile salts are most common. The first pa rr of this paper focuses on work related to the elucidation of mechanisms o f action of bile salts in buccal permeation enhancement of various drugs an d mucosal irritation, In the second part, results showing the enhancing eff ect of chitosan on buccal permeation of hydrocortisone, a commonly used top ical oral anti-inflammatory agent, and transforming growth factor beta (TGF -beta), which is a bioactive peptide to which the oral mucosa is relatively impermeable is presented. (C) 2001 Elsevier Science B.V. All rights reserv ed.