Mucoadhesive drug delivery systems: a promising non-invasive approach to bioavailability enhancement. Part I: biophysical considerations

ABSTRACT

Introduction

Mucoadhesive drug delivery systems (MDDS) are specifically designed to interact and bind to the mucosal layer for localized, prolonged, and/or targeted drug delivery. Over the past 4 decades, different sites have been explored for mucoadhesion including the nasal, oral, and vaginal cavities, the gastrointestinal tract and ocular tissues.

Areas covered

The present review aims to provide a comprehensive understanding of different aspects of MDDS development. Part I focuses on the anatomical and biological aspects of mucoadhesion, which include a detailed elucidation of the structure and anatomy of the mucosa, the properties of mucin, the different theories of mucoadhesion and evaluation techniques.

Expert opinion

The mucosal layer presents a unique opportunity for effective localization as well as systemic drug delivery via MDDS. Formulation of MDDS requires a thorough understanding of the anatomy of mucus tissue, the rate of mucus secretion and turnover, and the physicochemical properties of mucus. Further, the moisture content and the hydration of polymers are crucial for interaction with mucus. A confluence of different theories used to explain the mechanism of mucoadhesion is useful for understanding the mucoadhesion of different MDDS and their evaluation is subject to factors, such as the site of administration, type of dosage form, and duration of action.

KEYWORDS:

• Mucoadhesion
• theories of mucoadhesion
• mucin
• thiomers
• wetting theory
• interpenetration
• texture analyzer
• mucin-mimetic hydrogels
• in vitro-ex vivo mucoadhesion
• oral mucoadhesive

Article highlights

• The biophysical properties of mucin are critical to the performance of MDDS and are discussed in detail in the manuscript.

• The mucus layer is under constant turnover. The turnover rate is dependent on several anatomical and physiological factors, such as site of action, pathological conditions, and various normal physiological processes, such as peristalsis.

• Mucoadhesion is explained by five theories viz., wetting theory, interpenetration theory, fracture theory, adsorption theory, and electronic theory. No single theory can explain the mucoadhesion of different polymers, but rather a combination of two or more theories is used.

• A number of techniques are utilized to evaluate the strength of the mucoadhesive bond. Selection of an appropriate technique is dependent on the formulation, route of administration, and the type of information required. Combination of different techniques is found to be beneficial.

• A detailed review on the applications of different tissues and animal models utilized to evaluate mucoadhesion is provided.

This box summarizes key points contained in the article.

Abbreviations

API active pharmaceutical ingredient

AFM atomic force microscopy

MDDS mucoadhesive drug delivery systems

W_A work of adhesion

W_C work of cohesion

GIT gastrointestinal tract

DLVO Derjaguin Landau Vervey Overbeek

NP nanoparticle

MRI magnetic resonance imaging

IVIVC in vitro in vivo correlation

DLS dynamic light scattering

ΔG_totol total energy of adhesion

ATR attenuated total reflectance

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.

Additional information

Funding

This work was supported by the University of Connecticut Pfizer Distinguished Chair in Pharmaceutical Technology funds.