In vivo, ex vivo and in vitro assessment of buccal permeation of drugs from delivery systems

ABSTRACT

Introduction: Buccal mucosa has been described as an attractive site for local and systemic drug delivery, owing its accessibility, safety, and excellent blood supply. The absorption of drugs through buccal mucosa has been assessed by in vivo, ex vivo and in vitro permeability studies, using animal and cell-based models with close resemblance to the human buccal mucosa.

Areas covered: This paper focuses on the current in vivo, ex vivo and in vitro permeability studies to analyze the absorption of compounds of interest through buccal mucosa, as well as their advantages and limitations in the preclinical studies of the drugs absorption profiles. The techniques for preparation and preservation of the animal buccal tissue are also discussed to evaluate their interference in the integrity and permeability of the tissues.

Expert opinion: Overall, the permeability studies have been useful to evaluate the drugs absorption and to clarify the mechanism of transport of drugs across human buccal mucosa, as well as to explain the enhancement of permeability provided by certain dosage forms. Currently, several researchers have demonstrated particular interest in ex vivo permeability studies, due to their effectiveness in the evaluation of drug absorption and low costs in the acquisition of buccal mucosa samples.

KEYWORDS:

• Oral cavity
• drug delivery systems
• permeability studies
• animal models
• ex vivo studies

Article highlights

• Buccal mucosa is mainly used as an alternative delivery route for drugs highly susceptible to stomach and liver degradation.

• The porcine buccal mucosa is considered the standard animal model for permeability studies, due to its close resemblance with human buccal mucosa.

• The dermatomization and the cryopreservation are the recommended techniques to prepare and preserve the buccal mucosa, respectively.

• The studies currently applied to assess the absorption profile of drug through buccal mucosa are divided into in vivo, ex vivo, and in vitro permeability studies.

• Most of the permeability studies are performed ex vivo, due to the lower cost, the easier sample analysis and the lesser time-consuming compared to in vivo studies.

This box summarizes the key points contained in the article.

Acknowledgments

The authors acknowledge the support granted by national funds from FCT through project PTDC/BBB-NAN/3249/2014. This article is a result of the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was also financed by FEDER–Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.