Buccal thin films are a novel drug delivery system designed to dissolve or remain in the mouth until the desired removal. They provide rapid drug absorption through the buccal mucosa, which means consistent, stable dosing while avoiding first-pass metabolism, improving compliance and overall treatment outcomes for pharmaceutical companies and their patients.

Buccal thin films are small, flexible therapeutic single or multi-layered films infused with an active pharmaceutical ingredient (API). When placed on the inside of the cheek or between the cheek and gum, they dissolve quickly, offering a direct pathway to the bloodstream via the oral mucosa.

Buccal thin films avoid the digestive system and achieve higher bioavailability, ensuring faster onset and more controlled, consistent therapeutic effects.

READ MORE: Everything You Need to Know About Buccal Thin Films

In this blog, we will discuss the science behind buccal thin films, their advantages for pharmaceutical companies and the development strategies a company can employ to bring this product to market.

The Science Behind Buccal Thin Films

The effectiveness of buccal thin films depends on several factors, such as saliva composition, mucosal adhesion, disintegration time, mucosal permeability, and drug solubility. Understanding how these elements interact optimizes drug delivery, helping patients overcome unique physiological and pathological challenges.

Saliva

Saliva plays a central role in the effectiveness of buccal drug delivery systems. Composed primarily of water (99%), saliva also contains enzymes, mucins, electrolytes, and small molecules, all of which can influence drug dissolution and absorption. Variability in salivary pH is particularly significant, as deviations outside the normal range can lead to drug ionization, potentially impacting drug effectiveness. For instance, an acidic or basic environment can alter the solubility and bioavailability of certain drugs. As a result, understanding and accounting for the salivary pH range becomes critical in product development, influencing both the formulation and design of buccal films to ensure consistent and effective drug release.

The salivary buffering system—comprised of proteins, phosphates, urea, and bicarbonates—helps maintain pH stability, reduces bacterial growth, and supports oral health. During the design phase of buccal delivery systems, manufacturers must account for these buffering mechanisms to ensure that the formulation remains stable and performs optimally across varying pH conditions in the oral cavity.

The flow of saliva over the surface of buccal films facilitates thin film disintegration and, subsequently, drug dissolution and absorption. However, conditions like dry mouth (xerostomia) can impede drug delivery by reducing the amount of saliva available to dissolve and transport the drug. Factors such as olfactory, gustatory, or mechanical stimulation can alter saliva’s characteristics, including pH, viscosity, and flow rate, further influencing drug performance.

Surface Area and Drug Absorption

The buccal mucosa offers a unique environment for drug delivery due to its accessible surface area and permeability. For designed products, the buccal surface area is approximately 106 cm². This buccal mucosal surface is coated with a thin salivary film, typically 70-100 microns thick, which can influence drug diffusion. FDA-approved buccal thin film products typically range in size from 1.2-6.5 cm², highlighting the targeted application of the films.

Drugs absorbed through the buccal mucosa bypass the liver’s first-pass metabolism by entering systemic circulation via the jugular vein, allowing for more efficient drug delivery. The buccal epithelium is highly permeable—up to 4,000 times more than skin—allowing small lipophilic molecules to pass paracellularly and hydrophilic molecules to diffuse transcellularly. However, larger macromolecules face challenges due to tight junctions and enzymatic activity within the mucosal layer.

Drug Solubility and Permeability Challenges

A drug’s permeability depends on its molecular properties. Lipophilic drugs exhibit superior permeability by passing through the intercellular space between cell membranes, but they often face challenges with solubility, limiting the amount of drug absorbed.

Conversely, hydrophilic drugs dissolve more easily in aqueous saliva environments but struggle with permeability. This duality requires careful consideration during formulation development to optimize solubility and permeability for effective drug delivery.

Pathological Influences

Diseases and physiological conditions affecting the oral cavity can significantly influence the performance of buccal films. Conditions like xerostomia, which impacts one in four older adults, lead to reduced salivary flow, altering salivary pH, viscosity, and composition. These changes can impair drug dissolution and absorption, as well as contribute to secondary oral issues such as dental caries, periodontal disease, and dysphagia. To mitigate the effects of dry mouth, product labels often recommend that patients moisten or drink water before film application, ensuring sufficient saliva for film disintegration and optimal drug delivery.

Disorders such as asthma, cystic fibrosis, diabetes, and malnutrition can also alter salivary properties in general populations, impacting drug delivery outcomes. Similarly, systemic conditions like hyperthyroidism, pregnancy, or venous abnormalities can disrupt the jugular venous flow, affecting the systemic absorption of buccally administered drugs. In such cases, product instructions may advise patients to hydrate their mouths or use saliva-stimulating agents to support film effectiveness and promote better absorption. These measures ensure that patients with varying health conditions can achieve the intended therapeutic effects.

Buccal Thin Film Components

Buccal thin films are designed for efficient and directed drug delivery through the buccal mucosa. These films contain carefully formulated single or multiple layers, each vital in ensuring mucoadhesion, drug release, controlled disintegration/dissolution, protection of the active layer, and patient comfort. If avoidance of gastrointestinal side effects is required, the buccal film can be designed to be removed after a specified period to avoid swallowing a significant amount of API.

Here’s a breakdown of the key elements of buccal thin films:

1. Mucoadhesive Polymers

Mucoadhesive polymers form the backbone of buccal thin films, enabling adhesion to the buccal mucosa. These polymers often possess functional groups capable of hydrogen bonding, sufficient flexibility, and the ability to interact with mucus through electrostatic forces or diffusion. For instance:

  • Cationic Polymers like chitosan adhere through electrostatic interaction with the negatively charged mucin.
  • Non-Ionic Polymers like poly(vinyl alcohol) penetrate mucus gels, enhancing adhesion.
  • Thiolated Polymers (Thiomers) form covalent disulfide bonds with mucin, creating a stronger attachment.

Typically, a blend of mucoadhesive polymers is used to optimize drug release, mechanical properties, and film flexibility. Adjusting polymer ratios, as in the case of Carbopol and Eudragit blends, allows manufacturers to control swelling behavior and drug diffusion rates.

2. Drug Matrix

The drug matrix, which contains the active pharmaceutical ingredient (API), can exist in various forms, such as solid-state or amorphous drug matrices. 

This layer determines the release profile of the drug:

  • Immediate Release: Films with hydrophilic polymers facilitate rapid drug release due to water absorption.
  • Directed Release: Hydrophobic polymers create a barrier, slowing the release of the drug over an extended period.

The choice of polymer blend and API-solvent interactions greatly influences the therapeutic effectiveness of the buccal film.

3. Plasticizers

Plasticizers improve the mechanical properties of buccal thin films, such as tensile strength, folding endurance, and elasticity. They enhance the flexibility and comfort of the film, making it more adaptable to the movements of the oral cavity. Common plasticizers include:

  • Glycerol: A widely used option that improves flexibility and in-mouth feel.
  • Propylene Glycol: Offers similar benefits and good compatibility across polymer systems.

The selection of a plasticizer and its concentration directly affects drug release rates and patient experience.

4. Backing Layer

The backing layer provides the film with structural integrity and protects it from environmental factors such as moisture or physical damage during application. Depending on the therapeutic requirement, it may be designed to disintegrate over time or be insoluble and structurally sound for ease of buccal film removal after the intended therapeutic time.

5. Release Liner

The release liner is an optional layer, removed before application, ensuring the buccal film product remains intact and uncontaminated. It is crucial for maintaining the stability of sensitive APIs and can prevent the unacceptable diffusion of the API into the primary package during storage.

Drug Delivery and Release Considerations

The effectiveness of buccal thin films relies on optimizing their composition to overcome the barriers of the buccal mucosa. Critical factors include:

  • Mucoadhesive Strength and Buccal Residence Time: Strong adhesion to the buccal tissue ensures prolonged contact with the mucosa for sustained drug delivery.
  • Swelling and Gel Formation: Hydrophilic polymers create a gel barrier that enables drug solubility, regulates drug diffusion, and enhances residence time.
  • Drug-Polymer Interaction: Proper film formulation minimizes drug-polymer binding that could impede drug release.
  • Penetration Enhancers: Improvement in drug mass transport through the buccal tissue can be facilitated by various GRAS excipients that fluidize the intercellular lipid matrix, decreasing the diffusion resistance of the API.

By carefully balancing these components, buccal thin films provide an innovative solution for effective, patient-friendly drug delivery tailored to therapeutic needs.

Development Challenges

The development and manufacturing of mucoadhesive buccal films involve numerous complexities that must be addressed to achieve high-quality, effective, and safe dosage forms. Manufacturing techniques—such as solvent casting, hot melt extrusion, inkjet printing, and 3D printing—offer distinct advantages but also come with unique technical challenges.

Solution/Suspension Casting

Liquid intermediate casting is one of the most widely used techniques, favored for its simplicity and cost-effectiveness. This film manufacturing method is divided into solution casting, where all ingredients are dissolved in the solvent or solvents, and suspension casting, where the API is insoluble and uniformly dispersed before film drying. The solvents used for casting can be aqueous or organic.

However, the use of volatile organic solvents introduces environmental and toxicity concerns, requiring careful handling, disposal, and adherence to stringent regulatory safety standards. Additionally, achieving dose uniformity across thin films remains a persistent challenge, primarily due to the risk of air bubble entrapment during mixing, which can impact the coating process.

Hot Melt Extrusion

Hot melt extrusion offers a solvent-free, continuous process that improves content uniformity and is suitable for non-heat-liable APIs. However, its use is limited by the compatibility of the APIs with the formulation excipients and by high temperatures and pressures. 

Challenges such as weight variation, drug degradation, and potential for agglomeration during extrusion must also be addressed to ensure consistent film quality.

Inkjet Printing

Inkjet printing enables exact dosing in personalized medicine applications, making it a promising technology for buccal thin films. These liquid-based formulations require a solvent vehicle similar to solution casting.

However, inkjet printing also presents technical challenges, including nozzle clogging, the need for highly potent drug substances, and difficulties in maintaining long-term mechanical stability. Additionally, ensuring proper solvent drying without compromising film integrity adds to production complexity.

3D Printing

3D printing technologies, particularly Fused Deposition Modelling (FDM) and Semi-Solid Extrusion (SSE), are unlocking new possibilities for buccal film formulation. Like hot melt extrusion, FDM requires high temperatures to melt the polymer, limiting its compatibility with heat-sensitive APIs. Additionally, it faces challenges with rapid solidification and precise temperature control. 

SSE, while operating at lower temperatures, requires meticulous drying to prevent deformation or shrinkage. Both methods also demand advanced rheological characterization to optimize formulation consistency and process parameters, particularly for mucoadhesive applications.

Micro-Depositing

Micro-depositing is an emerging technique that enables precise deposition of small quantities of formulation material onto substrates, offering highly accurate dosing. However, it presents challenges, including ensuring consistent droplet formation and placement, as irregularities affect dose delivery. Additionally, the complex and costly equipment needed and the difficulty of maintaining high throughput without sacrificing quality complicates production.

Despite these hurdles, micro-depositing continues to evolve, with recent advancements improving dosing accuracy and bioavailability. These innovations have led to the highest bioavailable, FDA-approved buccal thin films, achieving 72% to 82% bioavailability. This sets a new industry standard for therapeutic effectiveness, showcasing micro-depositing’s ability to overcome technical barriers. The breakthrough is also patent-protected until 2039, securing its long-term market impact.

Addressing Development Barriers

Overcoming these challenges requires innovative strategies tailored to the specific demands of buccal thin films. Solutions to the challenges must prioritize scalability, regulatory compliance, and formulation stability to ensure successful product development. 

Partnering with an experienced Contract Development and Manufacturing Organization (CDMO) specializing in buccal thin film delivery can provide the expertise and infrastructure needed to navigate these complexities. Such collaborations streamline the development process, ensuring robust, scalable manufacturing while meeting regulatory and market expectations.

Finding a Buccal Thin Film Partner

Developing buccal thin films requires formulation, process optimization, and large-scale manufacturing expertise. Partnering with an experienced team that understands every stage—from feasibility to full-scale production—ensures the final product meets rigorous safety, efficacy, and quality standards. 

The ideal partner will offer capabilities in formulation development, CMC (Chemistry, Manufacturing, and Controls) support, quality assurance, analytical testing, and commercial manufacturing to streamline and accelerate the process.

Formulation Development

A successful buccal thin film starts with an optimized formulation. An expert partner ensures the API’s compatibility with the film matrix, considering solubility, mucoadhesion, permeation enhancement and directed release to meet therapeutic goals. The focus is on creating a film that delivers safe, effective, patient-friendly treatment.

Chemistry Manufacturing & Controls Support

After finalizing the formulation, scalable and reliable manufacturing processes are developed. A trusted partner ensures scalability, consistency and stability during production, while meeting regulatory requirements, paving the way for clinical trials and commercialization.

Quality Support

Quality assurance ensures the safety and reliability of buccal thin films. Rigorous testing evaluates critical properties such as mucoadhesion, drug release, absence of degradation, and mechanical strength, ensuring the product consistently delivers therapeutic results and meets compliance standards.

Analytical Testing

Comprehensive testing validates the film’s performance and stability. This includes evaluating drug content uniformity, stability, dissolution rates, and mucosal permeability over time, ensuring the buccal thin film is effective and reproducible for patients in its intended storage condition and over its proposed shelf life.

Clinical, Registration and Commercial Manufacturing

After scaling up for clinical and product registration in support of regulatory approval, the final step is scaling up for commercial production. A knowledgeable partner transitions seamlessly from development to manufacturing, maintaining efficiency and high quality in accordance with regulatory requirements. This ensures buccal thin films meet market demand while retaining their therapeutic performance.

Partnering with a team specializing in buccal thin film development minimizes risks and accelerates timelines. By leveraging formulation, quality, and production expertise, you can confidently deliver innovative therapies to the market.

Conclusion

For pharmaceutical companies, buccal thin films present significant advantages, including rapid absorption, precise dosing, and bypassing the digestive system to improve bioavailability and reduce side effects. However, developing and manufacturing these films requires specialized expertise in formulation, regulatory compliance, and scalable production processes. 

Partnering with an experienced team that supports every stage—from feasibility studies to commercial manufacturing—ensures your buccal thin film is safe, effective, and tailored to patient needs. With the right partner, pharma companies can confidently market innovative, patient-centric therapies.

ARx is your patient-friendly, novel drug delivery partner. We specialize in oral and buccal thin film and transdermal patch strategies — all backed by tailored, full-scale development services. Contact us today to find the right delivery system for your API.