Mucoadhesion testing: practical guidance for quantitative characterisation

Mucoadhesion refers to the ability of a dosage form to adhere to mucosal tissues, such as those lining the gastrointestinal tract, oral cavity, nasal passages, rectum or vagina. By maintaining intimate contact with the mucosa, a mucoadhesive system can:

• Prolong residence time at a specific site
• Enhance local or systemic bioavailability
• Protect sensitive actives from harsh environments (for example gastric pH or enzymes)

Mucoadhesive drug delivery systems are already used clinically in the oral cavity and have been investigated for the treatment of stomach ulcers, cancer and a range of mucosal infections. Since most infections in humans and animals involve mucous membranes, the ability to retain pharmacologically active agents on mucosal epithelium for extended periods has clear therapeutic advantages.

This article focuses on how to measure mucoadhesive performance using a Texture Analyser, with emphasis on sample preparation, probe selection and interpretation of force-distance data.

Instrumentation and general test principles

The Texture Analyser has become a widely used platform for quantifying bioadhesive and mucoadhesive bond strength. It provides controlled:

• Approach speed and contact force
• Dwell time under load
• Withdrawal speed and debonding profile

The same general principles used for transdermal adhesive testing apply to mucoadhesion:

• A probe (often cylindrical) is brought into contact with the substrate (tissue or model surface) under a defined normal force for a defined time.
• After this dwell period, the probe is withdrawn and the resulting force-distance curve is recorded.
• Adhesive parameters are then calculated, such as:
  • Peak detachment force (N)
  • Work of adhesion (area under the curve, N·mm or N·cm)
  • Debonding distance (mm)
  • Tensile stress (N/cm²) based on known contact area

Different dosage forms can be assessed using appropriate probe and mounting combinations:

• Solid dosage forms (tablets, films, devices)
• Semi-solids (ointments, gels, hydrogels)
• Systems that solidify in situ on contact with the target tissue

Mucoadhesion Rig for near-physiological conditions

The Mucoadhesion Rig, developed at the University of Strathclyde and now widely adopted in Europe, enables testing under conditions that mimic in vivo environments more closely than simple ambient tests. The rig allows:

• Mounting of tissue samples in a vessel containing temperature-regulated simulated gastric fluid or other physiological media
• Controlled lowering of a probe carrying the formulation (solid or semi-solid) onto the tissue
• Measurement of the debonding profile while the tissue remains hydrated and at controlled temperature

This arrangement is particularly useful when evaluating gastroretentive systems or dosage forms intended for specific mucosal sites where fluid environment and temperature strongly influence adhesion.

Sample preparation strategies

Biological mucosa

Porcine mucosa is commonly used as a surrogate membrane for bioadhesion measurements. Because biological tissues are inherently variable, careful and consistent handling is critical:

• Standardised harvesting and trimming of tissue
• Controlled storage conditions (for example temperature, time, medium)
• Equilibration to test temperature and hydration state before measurement

Where tissue is tested in ambient conditions without immersion in fluid, a fixed volume of buffer or simulated physiological medium is typically pipetted onto the mucosa to standardise hydration prior to testing.

Artificial and solid model substrates

Artificial membranes and solid substrates (stainless steel, aluminium, acrylic, glass) have also been used in mucoadhesion studies. Although the absolute adhesion to these materials differs from that to mucosal tissue, relative changes in adhesion often track formulation differences effectively. Advantages include:

• Simplified sample handling and cleaning
• Improved reproducibility of surface properties
• Easier implementation in routine screening or quality control

Such substrates can be useful for comparative or developmental work, particularly where the objective is to rank formulations rather than to replicate absolute in vivo forces.

Probe selection and dosage form mounting

Typical probe sizes

For bioadhesive and mucoadhesive testing, cylindrical probes of acrylic or similar materials with diameters in the range of 7 to 10 mm are common. The known probe or dosage form contact area allows conversion of detachment force to tensile stress (N/cm²).

Solid dosage forms and films

Solid samples such as tablets or films are usually attached to the underside of the upper probe using:

• Cyanoacrylate adhesive
• Thin, stiff double-sided tape
• The mounting method must:
• Ensure secure attachment during debonding
• Avoid significant compliance or flexing in the adhesive layer, which would distort the force-distance curve

Powders

For powders, a practical approach (as described by Bredenberg and co-workers) is:

1. Fix a double-sided adhesive tape to the underside of the probe.
2. Immerse the probe in a bed of powder.
3. Gently shake to remove excess and achieve a monolayer of particles.

The double-sided tape should be as thin and rigid as possible, to minimise deformation during debonding and preserve sensitivity to powder–substrate adhesion rather than tape compliance.

Gastrospheres and particulate systems

Gastrospheres and similar particulate systems have been tested by:

• Pre-immersing samples in simulated gastric fluid for defined time intervals
• Covering both the probe and test platform with simulated gastric membrane
• Applying a standard contact force (for example 2 N) for a fixed dwell time
• Measuring detachment force as an indicator of bioadhesion

This approach enables time-dependent studies of mucoadhesive performance after exposure to physiological conditions.

Hydrogels and gel-based mucoadhesive systems

Mucin disc approach

Hydrogel mucoadhesion has historically been less well characterised than that of solid dosage forms. One method reported in the literature involves:

• Preparing mucin discs and attaching them to the underside of a cylindrical probe using double-sided tape
• Lowering the mucin-coated probe onto the surface of the hydrogel formulation
• Applying a defined normal force for a predetermined contact time
• Measuring the force required to detach the mucin disc from the gel

This method enables comparison of gel formulations based on their interactions with a mucin-rich surface.

Gel Mucoadhesion Probe

An alternative, now widely used, approach is the Gel Mucoadhesion Probe. This probe has:

• An inverted cone geometry at the tip
• Machined concentric grooves that promote retention of a defined volume of gel on the probe surface

Key features of this method:

• Hydrogel is applied to the probe using a syringe for accurate volume control.
• A PTFE collar can be fitted to support larger gel volumes while the gel is loaded or set, then removed prior to testing.
• The gel-coated probe is brought into contact with tissue or model membrane for a fixed dwell time and force, then withdrawn to characterise mucoadhesion.

This configuration provides good control of gel volume and contact area, enabling more reproducible comparison across formulations.

Test sequence and curve acquisition

In a typical mucoadhesion test:

1. The probe or dosage form is aligned above the tissue or substrate.
2. The probe descends at a controlled speed until the specified contact force is reached.
3. The system maintains this force for a dwell time to allow wetting, polymer chain interpenetration or hydrogen bonding.
4. The probe then withdraws at a defined speed while force is recorded as a function of distance.

The resulting force-distance curve displays:

• Initial compressive phase
• Transition to zero force
• Tensile region with peak force and subsequent decay until complete debonding

These curve shapes have been described in detail by Chuang and co-workers and are broadly applicable to most bioadhesive systems.

Beyond peak force: advanced analysis of debonding behaviour

Relying solely on peak detachment force can be misleading. Two products may exhibit similar peak forces yet behave very differently during debonding. More informative parameters include:

• Work of adhesion: total area under the tensile portion of the curve, reflecting the energy required to completely separate the surfaces.
• Debonding distance: displacement from the onset of tension to final separation, related to filament formation and stringiness.
• Pre- and post-peak regions: areas and distances before and after the peak force, which can be used to infer cohesive versus adhesive failure modes.

For tensile stress (N/cm²), the detachment force is divided by the known contact area of the tablet, gel, film or powder-coated probe.

Importance of work of adhesion

For dosage forms that must resist complex and sustained dislodging forces, such as mucoadhesives targeting throat linings, the area of work is often a better indicator of clinical robustness than peak force alone.

• Realistic dislodging forces from swallowing, food bolus movement and muscle action are typically distributed and time dependent.
• Few physiological events impose very sharp, high peak forces.
• A high work of adhesion indicates that the system can tolerate persistent shear and tensile stresses before failure.