Carbamazepine Transbuccal Delivery: The Histo-Morphological Features of Reconstituted Human Oral Epithelium and Buccal Porcine Mucosae in the Transmucosal Permeation

Abstract

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

Effect of Freezing and Type of Mucosa on Ex Vivo Drug Permeability Parameters

“…The bioavailability and absorption of this drug are limited due to their low solubility in water (14), and thus alternative routes for the CBZ delivery have recently been proposed. 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 (15), hence this drug was selected for the tests.…”

Histological features of oral epithelium in seven animal species: As a reference for selecting animal models

“…Morphological features exert a tremendous influence on the translatability of the experimental outcome of the animal model (Campisi et al, 2008). Keratinized oral epithelium has low permeability, which compromises investigations related to oral delivery; keratinized oral A C C E P T E D M A N U S C R I P T…”

Ex Vivo Correlation of the Permeability of Metoprolol Across Human and Porcine Buccal Mucosa

“…Porcine buccal mucosa has many similarities to human buccal mucosa with respect to composition and histology . The porcine ex vivo permeability model has been compared numerous times with a reconstituted human buccal epithelium model consisting of filter‐grown TR146 cells originating from a human buccal carcinoma, whereas only a single study has compared porcine and human ex vivo models . Nielsen et al compared the permeability of mannitol and testosterone in different ex vivo models, that is, porcine, human, and monkey buccal mucosa.…”