Mucoadhesive buccal films: everything you need to know about API requirements

Introduction to Mucofilm®: Mucoadhesive buccal films (MBFs)

Oral films, are flexible, low-profile dosage forms designed to dissolve directly in the mouth.

They provide an innovative alternative to conventional oral drug delivery systems, offering ease of administration, rapid onset of action, and improved patient compliance, making them particularly attractive for patient-centric formulations. Oral films are especially beneficial for children, the elderly, and patients with swallowing difficulties or specific medical conditions.

Depending on the intended route of administration, the film can be used as:

• Fast-dissolving oral films, which disintegrate quickly in the mouth without needing water (Rapidfilm®), the active ingredient is usually swallowed with saliva. In this case, drug absorption mainly occurs in the gastrointestinal tract.
• Mucoadhesive buccal films (Mucofilm®), designed to adhere to the mucosa (sublingual or buccal) and deliver APIs in a controlled and precise manner. The drug is absorbed directly through the mucosa, bypassing the digestive tract and the liver. That means a faster and more predictable effect, and often a lower dose is needed.

In this article, we focus exclusively on mucoadhesive buccal films (MBFs), such as Mucofilm® by AdhexPharma.

Key Benefits of Mucofilm®

Mucofilm® combines the benefits of mucoadhesive buccal films while offering unique flexibility for both patients and drug developers, particularly for transmucosal drug delivery.

Benefits for patients:

• Easy and stress-free administration: No chewing or swallowing is required, making it simple to use. The Mucofilm® technology is particularly suitable for vulnerable populations, including children, the elderly, and patients with dysphagia. Orodispersible Films: An Alternative to Syrups for Neonates and Infants?
• Rapid onset of action – Close and prolonged contact with the mucosa allows faster therapeutic effects. Depending on the formulation, the drug can be released quickly for rapid action or in a controlled manner to achieve a constant uptake of the drug
• Bypass of liver metabolism – Transmucosal absorption avoids the first-pass effect, improving therapeutic efficiency.
• Often higher systemic bioavailability – Typically resulting in improved API exposure and clinical performance.
• Lower dose requirements – Enhanced bioavailability may allow dose reduction compared to conventional oral administration.
• Discreet self-administration – Ultra-lightweight and virtually undetectable once applied, Mucofilm® supports comfortable and private use.
• Convenient storage and transport – Thin films are compact, lightweight, and easy to handle.

Benefits for drug developers

• Innovative product opportunities – Mucofilm® enables differentiated, patient-centric dosage forms.
• Flexible delivery options – Suitable for both local treatment in the oral cavity and systemic transmucosal delivery, depending on the API and therapeutic need. Overview: Oral films and their administration routes
• Improved bioavailability – Supports optimization of challenging APIs with limited oral absorption.
• Lifecycle management support – Enables reformulation strategies and product line extensions.
• Scalable industrial manufacturing – Proven film production technologies ensure precise dosing and reliable scale-up.

Market overview

The growing interest in oral film technologies is reflected in market dynamics: the global oral thin films market is estimated at around USD 3.30 billion in 2025 and is projected to grow to approximately USD 5.21 billion by 2030, highlighting the strong adoption of patient-friendly and innovative drug delivery solutions.

API requirements for transmucosal delivery

Core Physicochemical Criteria

Successful transmucosal delivery via mucoadhesive buccal films (MBFs) relies heavily on the physicochemical properties of the API. Understanding these parameters early in development is crucial to ensure efficient absorption and optimal therapeutic performance.

• Molecular weight: APIs with a molecular weight below approximately 500 Da generally show more favorable transmucosal permeation. However, this threshold is not absolute, and larger molecules such as small biologics, peptides, or certain vaccines may also be suitable for transmucosal delivery when supported by optimized formulation strategies and appropriate delivery systems.
• Lipophilicity (Log P): Lipophilicity, expressed as Log P, should be moderate and is typically preferred to enable efficient permeation through both the mucosal surface and lipid barriers. Balancing hydrophilicity and lipophilicity is key for stable absorption.
• Ionisation / pKa: The degree of ionisation of an API, as determined by its pKa in relation to saliva pH (~6–7), influences buccal and transmucosal absorption. Predominantly non-ionized drugs permeate lipid membranes more readily; however, effective absorption of other molecules can also be achieved with appropriate formulation strategies.
• BCS class & solubility: Both solubility and permeability are critical for ensuring proper film performance. Poorly soluble APIs may require specialized strategies, such as solubilization techniques, nanostructured carriers, or multi-layer film design, to achieve consistent dosing and bioavailability.

Low-to-moderate dose APIs are best suited for mucoadhesive films. Higher doses may be accommodated through multilayer designs or specialized technologies.

Early assessment of API properties is critical to ensure feasibility and guide formulation development.

Permeation Factors and the Role of MCGs in the Buccal Mucosa

The buccal mucosa, composed of non-keratinized epithelium, lamina propria, and submucosa, is covered by a thin mucus layer that supports mucoadhesion and drug retention. In the upper third of the epithelium, naturally occurring membrane-coated granules (MCGs) create lipid-rich intercellular spaces that regulate the diffusion of hydrophilic and lipophilic drugs. Polar lipids facilitate hydrophilic drug passage, while non-polar lipids form small barriers for lipophilic compounds—creating a “cell–lipid mosaic” crucial for transmucosal absorption.

Early ex vivo permeation studies, often using porcine buccal tissue, provide valuable insights into absorption behaviour and support rational formulation design, helping to optimize drug release and transmucosal permeation.

Enhancing patient experience through sensory optimization

Patient acceptability is a key factor in the success of mucoadhesive buccal films. Taste, pH, and local tolerance must be carefully considered to ensure comfortable and compliant use.

The disintegration rate of the film and the choice of mucoadhesive polymers directly influence residence time on the mucosa and the onset of action. Optimizing these sensory and mechanical properties ensures that the film remains in place long enough to deliver the API effectively while maintaining a pleasant, unobtrusive experience for the patient.

By addressing sensory aspects early in development, formulators can maximize patient adherence, improve therapeutic outcomes, and differentiate the product in the marketplace.

Regulatory & CMC Constraints

Ensuring regulatory compliance and robust CMC (Chemistry, Manufacturing, and Controls) is essential for successful mucoadhesive oral film development. Key considerations include:

• API-excipient compatibility: The API must be compatible with the selected film formers, plasticizers, and other excipients to maintain stability, efficacy, and safety.
• Stability and analytical methods: Early development should include stability studies and the development of reliable analytical methods (e.g., HPLC, LC-MS) to quantify the API and monitor formulation integrity over time.
• GMP compliance: All development and manufacturing steps must adhere to Good Manufacturing Practices, ensuring consistent quality and regulatory readiness.

Conducting these assessments early in the project helps mitigate risks, avoids costly delays, and provides a solid foundation for subsequent formulation optimization, scale-up, and clinical supply.

Key development aspects include:

• API–excipient compatibility
• Stability studies and validated analytical methods
• GMP-compliant development and manufacturing

Addressing these factors early minimizes risk and facilitates smooth scale-up and regulatory progression.

Conclusion

Mucofilm® represents an innovative and patient-friendly alternative to conventional oral dosage forms. By enabling precise transmucosal delivery, rapid onset of action, and improved bioavailability, it supports effective therapy with optimized API exposure.

As a fully integrated CDMO, AdhexPharma offers end-to-end support from early feasibility through clinical and commercial manufacturing.

Ready to develop your mucoadhesive buccal film and optimize API delivery?

Reach out to us at contact@adhexpharma.com and start your project today!