The authors review the ultra-structural aspects and permeability features of normal human oral mucosa, after having recently tested and used it as a new site of systemic drug delivery. The pertinent scientific literature from 1975 through 2009 has been analysed and discussed. Buccal epithelium is a relatively permeable, robust non-keratinized tissue and blood vessels drain directly into the jugular vein; due to its particular features, it has been of increasing interest to researchers as an alternative site of drug administration. The review describes the structure and function of the buccal mucosa, the rationale for transbuccal drug delivery and the main transmucosal drug delivery systems. Recent studies have investigated the delivery of a variety of drugs through the buccal mucosa in order to assess both local and systemic, either positive or adverse, effects. In conclusion, buccal mucosa may be considered a promising site for effective, safe and non-invasive transmucosal sustained drug delivery.

Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer.Buccal delivery offers a feasible alternative to parenteral delivery and many advantages to per os administration, e.g. reduced first pass metabolism, reduced drug decomposition and adverse effects, improved drug bioavailability, and often a more rapid onset of therapeutic effect (1).Carbamazepine (CBZ) is a drug which could be very attractive if delivered transbuccally. CBZ is really useful in controlling neuropathic pain (2) and it is currently delivered per os, using doses ranging from 200-600 mg/die administered in divided doses. Following peroral administration, absorption and