Mucoadhesion is a type of bioadhesion in which two materials, at least one of which is a mucus or a mucous membrane, are held together for extended periods by interfacial forces. This phenomenon can apply to a range of tissues in the human body, including the gastrointestinal tract (GI-tract), vagina, rectum and eyes, as well as the inside of the nose, mouth and throat.

The wetting of a mucoadhesive material on contact with the mucosa enables interpenetration between polymer chains in both, which then leads to the formation of bonds between the entangled chains. These bonds hold the two materials together until they are weakened or overcome by stronger forces.

Drug formulations can be designed with these mucoadhesive properties in mind. This can allow them to adhere to and remain on a target mucous membrane for longer.

The benefits of mucoadhesion
Mucoadhesion has the potential to improve multiple types of pharmaceutical products and provide benefits not just to formulators, but to patients. There are numerous ways mucoadhesion can enhance the performance of an end product. Key benefits include:

Prolonged retention at the site of action
Mucoadhesion allows the drug formulation to be applied directly to the target site and remain there for a longer period than can be achieved with a non-mucoadhesive formulation.  This can enhance drug delivery and prolong drug action for both localized (the dosage form at the site of action) or systemic (the dosage form at the absorption site) delivery.

Lubrication and protection of the target tissue
Mucoadhesion doesn’t just hold a drug at a specific target site, it can also enable a formulation to coat a mucous membrane, providing a lubricating cover for the tissue. As a result, it can help a product soothe irritated tissue, such as a sore throat, or help relieve symptoms of disorders, such as dry mouth. It can even provide long-lasting protection of damaged or sensitive tissue, such as a canker sore in the mouth, from contact with fluids that can cause pain or delay healing.

Enabling more convenient, non-invasive products
Mucoadhesion can aid a variety of dosage forms, for use in multiple areas of the body, enabling more effective drug delivery. Because of this enhanced delivery, mucoadhesion can facilitate the creation of non-invasive, more convenient dosage forms that would otherwise not be possible. For example, topical mucosal products formulated without consideration of mucoadhesive properties may not deliver enough drug effectively to be viable. This may require a formulator to change course and create an oral or injectable product instead.

However, oral drug products and injectables are not always preferred by the patient when compared to topicals. Oral drug products may be difficult to swallow and can irritate the gastrointestinal tract. Similarly, injectable drug products can be painful and inconvenient for patients, as they can often only be administered by a medical professional.

If mucoadhesion is effectively formulated into a drug product, more convenient and less painful dosage forms can be successfully developed, for example:

• Topical gels and emulsions
• Toothpastes and mouthwashes
• Patches and films
• Lozenges and buccal tablets
• Oral solutions and suspensions
• Eye drops or contact lenses
• Nasal sprays 

Many of these dosage forms are preferred by patients compared with oral drug products or injections. They can be more convenient and more comfortable to administer, which can help optimize patient adherence to a dosing regimen. Enhancing drug delivery via mucoadhesion can ensure that these dosage forms offer the same high therapeutic effect as traditional dosage forms, making them a viable alternative treatment for patients.

How to harness mucoadhesion in your formulation
Given the potential benefits of mucoadhesion, it is no surprise that formulators are considering how to instill mucoadhesive properties into their drug products. But how can they achieve this effectively?

The key to achieving the right mucoadhesive profile for the unique needs of a pharmaceutical product lies in use of excipients. There are several polymers used across the pharmaceutical industry to impart mucoadhesion to drug formulations, such as carbomers like LLS Health’s Carbopol polymers and Noveon polycarbophil.

Initial considerations in designing a mucoadhesive formulation
When creating and developing a mucoadhesive drug formulation, there are a number of key considerations to take into account for ensuring the target drug product profile is reached:

The active pharmaceutical ingredient (API)
API considerations will provide the basis for dosage form and excipient selection in the formulation process. The physicochemical properties (e.g., solubility, permeability, and stability) together with dose strength requirements of the API will play a key role in the formulation of mucoadhesive drug products. A formulator needs to consider whether an API is suitable for mucosal drug delivery, i.e. is it permeable. In general, smaller molecules are most likely to be readily absorbed through mucous membranes. Models have been developed to predict permeability of the API as a function of its physicochemical characteristics. A multi-API product will also have unique formulation requirements to ensure proper release at the intended site of action.

The excipients used
The design of a mucoadhesive formulation requires the presence of an excipient that imparts mucoadhesive properties and ensures prolonged contact between the drug product and the mucosa. In addition, the selection of the other inactive ingredients is extremely important given that they may alter the API, release rate, mucosal permeation, and stability, among other properties. A number of polymers are widely used across the pharmaceutical and healthcare industries to create and enhance mucoadhesion in product formulations.

The site of delivery
The ultimate goal of any mucoadhesive formulation is to allow active pharmaceutical ingredients to be delivered and achieve desired therapeutic effect. It is therefore necessary to understand the target tissue, i.e the site of drug delivery. When designing a mucosal formulation, tissue penetration has to be considered, as not all surfaces are the same. For example, drug uptake for the rectum is different than for the inside of the nose.

Additionally, not only must a formulation be designed for the specific target mucosa, but it must also be optimized either for localized or systemic delivery as mucosal drug delivery can accommodate either. The sites of delivery for which mucoadhesive drug delivery can be considered include:

• Buccal
• Ocular
• Nasal
• Esophageal
• Vaginal
• Rectal

The dosage form
A range of mucoadhesive formulation types can be developed, from solid, to semi-solid, to liquid. The formulation base selected is dependent on the goal of the product set out in the Target Product Profile (TPP), and on the intended dosage form.

To choose the ideal dosage form for the TPP, it is important to consider the most appropriate route of administration to ensure sufficient exposure for the drug to have its intended therapeutic effect. A number of factors impact on this, including API stability and compatibility, as well as type of disease your product is intended to treat and the part of the body affected.

Patient convenience and adherence should also be taken into account. Ease of handling and administration at the required frequency even by patients with dexterity issues or visual impairments, as well as limited side effects, can ensure patients adhere to their treatment, maximizing its effectiveness.

Following the selection of the dosage form, it is possible to consider the specific mucoadhesive properties required for the formulation to achieve its TPP.

Mucoadhesion—instilled using the right inactive ingredients—can allow formulators to develop multiple dosage forms that are more effective and better meet patients’ needs.

The dosage forms the performance of which can be enhanced by mucoadhesion include:

• Topical gels and emulsions
• Patches and films
• Oral solutions and suspensions
• Eye drops
• Nasal sprays
• Lozenges and buccal tablets
• Toothpastes and mouth washes

Time to consider your product’s mucoadhesive performance
In an increasingly competitive global pharmaceutical market, considering mucoadhesion for a variety of dosage forms can do more than improve the effectiveness of the product and benefit patients. It can also help drug products stand out from other standard options.

LLS Health is an expert in helping companies to differentiate their OTC and Rx drug products by optimizing their mucoadhesive properties through the use of our polymers. With support from such expert partners, pharmaceutical companies can be confident their products will continue to distinguish themselves from the competition in a crowded market. 

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Dr. Liliana Miinea is Technology Manager at Lubrizol Life Sciences, Lubrizol Corporation