Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies

Eur J Pharm Sci. 2016 Jan 1:81:52-9. doi: 10.1016/j.ejps.2015.09.021. Epub 2015 Oct 3.

Abstract

The objective of the present study was to investigate the influence of preparation and storage conditions on the histology and permeability of different parts of porcine oral mucosa used for in vitro studies of transbuccal formulations. Fresh and frozen (-20°C and -80°C, with or without cryoprotectant) epithelia of porcine palatal, gingival, dorsum of the tongue, and buccal mucosa were submitted for histological analyses to determine the effects of storage conditions on barrier integrity. Permeation of lidocaine hydrochloride (used as a hydrophilic model drug) across fresh and previously frozen oral epithelium was measured in order to evaluate the barrier function. Histological evaluation demonstrated that the oral epithelium was successfully separated from the connective tissue, except for gingival mucosa. After storage under different conditions, all tissues presented desquamation of superficial layers and spherical spaces induced by the freezing process. The permeability of lidocaine hydrochloride varied among the fresh oral mucosa and generally increased after freezing. In conclusion, fresh epithelium from the buccal and dorsum of the tongue mucosa should be used for in vitro studies investigating hydrophilic drug transport when these are the desired clinical application sites. However, when the palate is the target site, both fresh and frozen (for up to 4weeks, without addition of cryoprotectant) samples could be used. The addition of glycerol as a cryoprotectant should be avoided due to increased lidocaine hydrochloride permeability.

Keywords: Diffusion; In vitro model; Oral mucosa drug delivery; Permeability.

MeSH terms

  • Anesthetics, Local / metabolism*
  • Animals
  • Cryoprotective Agents / pharmacology
  • Drug Evaluation, Preclinical / methods*
  • Freezing
  • Glycerol / pharmacology
  • Lidocaine / metabolism*
  • Mouth Mucosa / anatomy & histology
  • Mouth Mucosa / metabolism*
  • Permeability / drug effects
  • Specimen Handling / methods
  • Swine

Substances

  • Anesthetics, Local
  • Cryoprotective Agents
  • Lidocaine
  • Glycerol