The Measurement of Mucoadhesion/Bioadhesion

Mucoadhesion is the process by which a drug delivery device is designed to stick to a part of the gut or other mucosae, thus delivering drug to a precise site in the body for an extended period. This gives more effective treatment of some diseases and can also protect drugs from some of the harsh conditions in the body. Mucoadhesive drug delivery systems are used to treat several conditions in the mouth and have been investigated as treatments for stomach ulcers and cancer. The majority of infections affecting man and animals take place or start in mucous membranes. The ability to retain pharmacologically-active agents for extended periods of time on any mucosal epithelium, including those of the nose, mouth, rectum or vagina confers several potential therapeutic advantages.

Measuring mucoadhesion

The TA.XTplusC Texture Analyser has emerged as a useful tool for measuring bioadhesion bond strength. The determination of the adhesive properties of pharmaceutical dosage forms is important in their development and several methods have been developed for these measurements. Tests of solid dosage forms, semi-solids such as ointments and gels and even systems which solidify on contact with the target organ can be performed using alternative measuring probes. The measurement of adhesive properties has already been reviewed for transdermal adhesive products and the same adhesive test guidelines and curve analysis techniques apply for the measurement of mucoadhesion.

Developed at the University of Strathclyde, and since adopted by a number of groups in Britain and Europe, the Mucoadhesion Rig offers a number of advantages over systems previously used for the assessment of mucoadhesion. Where conditions close to those found in vivo are required, the Mucoadhesion Rig provides the ability to set-up the tissue samples in a vessel of temperature regulated gastric fluid and lower a probe with the attached solid or semi-solid dosage form onto the tissue.

Mucoadhesion Rig with heater stirrer on the TA.XTplus Texture Analyser; Gel mucoadhesion probe

Porcine mucosa is the membrane typically used for bioadhesive measurements. As the tissue itself is often inconsistent, the sample preparation does demand consistent harvesting, trimming, storing and environmental conditioning of the sample so as not to pose a barrier to the experimentation required to optimise the test methods. Artificial membranes have also been used as these simplify the sample preparation difficulties when using biological membrane.

Sample preparation and testing method techniques, however, vary depending upon the nature of the sample. The following points aim to provide an understanding of the alternative sample preparation methods, probe options and necessary method adjustments to assist in the design of custom tests, particularly for mucoadhesion testing.

Sample preparation and testing alternatives

The most common probe sizes and dimensions for bioadhesive testing are acrylic or similar cylinders with a diameter of 7-10 mm. Solid materials such as tablets and films (of standard section size) are usually attached to the underside of the upper testing probe using cyanoacrylate adhesive or double-sided tape.

The probe approaches the sample at a chosen speed and applies a chosen force to the mucosa for a chosen period of time so as to achieve a good bond between the two surfaces. After this time the probe withdraws from the mucosa and in doing so the adhesive force to detach the two surfaces is measured.

For the assessment of powders, the application of the powder can be performed by immersing the probe (with adhesive tape attached to the underside) into a powder bed and thereafter gently shaking the probe to remove any excess, to achieve a monolayer of particles. When selecting a double-sided tape the thinnest and stiffest tape possible should be chosen since the material must not be allowed to flex or loosen during debonding.

Samples of gastrospheres have been successfully tested by previously immersing in simulated gastric fluid for predetermined time intervals, covering both the probe and the test platform with simulated gastric membrane and measuring the bioadhesion (the force of detachment) of samples after applying a force of 2N.

The use of bioadhesive polymers in the formulation of dosage forms for mucosal drug delivery is receiving increasing attention. Researchers Skulason, Kristmundsdottir and Holbrook in the Faculty of Pharmaceutical Sciences at the University of Iceland developed a technique for evaluation of the adhesion of hydrogel compositions. The Gel Mucoadhesion Probe [B] consists of an inverted cone shape at its end which has machined concentric grooves. These grooves encourage the attachment of a controlled volume of hydrogel sample to the probe surface area. For constant gel volume application the use of a syringe is recommended. A PTFE collar is supplied to support larger volumes of hydrogel loading which is removed when the gel is set.

Where the mucosa is held in ambient conditions without suspension in, for example, gastric fluid, a fixed volume of buffer is generally pipetted onto the mucosa to standardise the hydration prior to testing.

Typical properties that can be obtained from a texture analysis graph and that are quickly obtained from the use of a macro in Exponent software:

Typical Texture Analyser graph with annotated properties of a mucoadhesion test

The success of the measurement of mucoadhesion/bioadhesion can be demonstrated in the latest round of published paper examples that use the Texture Analyser for its measurement:

Role of mucoadhesive polymers in retention of toothpaste in the oral cavity

Texture Analysis and Bioadhesive of a Hydrogel as Platforms for Herbal Gel in Sports Massage

Development of mucoadhesive modified kappa-carrageenan/pectin patches for controlled delivery of drug in the buccal cavity

Design of novel orotansmucosal vaccine-delivery platforms using artificial intelligence

A mussel-inspired wet-adhesion hydrogel with hemostasis and local anti-inflammation for managing the development of acute wounds

Herpes labialis: a new possibility for topical treatment with well-elucidated drugs

For more information on the measurement of Mucoadhesion, request our article.

There is a Texture Analysis test for virtually any physical property. Contact Stable Micro Systems today to learn more about our full range of solutions.

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For more information on how to measure texture, please visit the Texture Analysis Properties section on our website.

The TA.XTplusC texture analyser is part of a family of texture analysis instruments and equipment from Stable Micro Systems. An extensive portfolio of specialist attachments is available to measure and analyse the textural properties of a huge range of food products. Our technical experts can also custom design instrument fixtures according to individual specifications.

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