Advancements in Buccal Drug Delivery: Polymers and Their Applications

Introduction

Oral administration is perhaps the most popular method of medication administration among patients and doctors. There is currently no strong correlation between membrane permeability, absorption, and bioavailability, which means that many drugs cannot be effectively delivered through the conventional oral route due to our limited understanding of the biochemical and physiological processes involved in metabolism and absorption. This limitation is largely due to extensive pre-systemic clearance in the liver following administration. The need to develop alternate delivery methods arose from the challenges associated with parenteral administration and low oral availability of these medications. Therefore, various additional types of mucosae that are effective in absorbing drugs are being examined for this purpose. Transmucosal drug administration offers several benefits over oral delivery when aiming for systemic effects. Transmucosal routes include the linings of the nasal, rectal, vaginal, ocular, and oral cavities. For controlled-release dosage forms, the buccal mucosa is the preferred transmucosal route as it is easily accessible, has a broad area of smooth muscle, and is generally immobile.¹

Buccal drug delivery (BDD) is recognized for its potential to bypass the GI tract and hepatic first-pass metabolism, offering an efficient route for delivery of drug throughout the body. This method involves the administration of drugs across the buccal mucosa, the inner lining of the cheeks, allowing for direct absorption into the systemic circulation. The effectiveness of buccal drug delivery systems (BDDS) depends significantly on the use of appropriate polymers that can stick to the mucosal lining, sustain drug release, enhance permeation, and protect active ingredients from degradation.²

An additional advantage of this approach is the rapid regeneration of buccal mucosal cells. The buccal membrane has a lower surface area and low permeability, especially relative to the sublingual membrane, which are drawbacks of this drug delivery route. There is a total of 170 cm² of drug-absorption surface area on the oral cavity membranes, with approximately 50 cm² being non-keratinized tissues, such as the buccal membrane.³ The medicine is diluted over time due to the continuous emission of saliva, which ranges from 0.2 to 2 litres each day. The forced extraction of a dose form can occur if the patient swallows saliva, which can result in loss of medicine along with any suspended or dissolved components. One issue with BDD is the risk of choking on the delivery device if swallowed unintentionally. Patients may also experience difficulty taking the medication while eating or drinking due to the tablet shape. While there are certain drawbacks to this method of drug delivery, the benefits outweigh them, making BDDS a promising approach for future studies.⁴

Permeability Barrier of Oral Mucosa

 The permeability barrier plays a crucial role in main taining oral health by protecting underlying tissues from pathogens, irritants, and mechanical stress. It selectively regulates the transfer of nutrients and molecules across the mucosal surface.⁵

Structure of Oral Mucosa

The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises three layers.⁶

 Epithelium

The outermost layer, which forms the primary barrier against the external environment. It is predominantly stratified squamous epithelium, which can be either keratinized or non-keratinized depending on the area of the mouth.

Lamina Propria

A connective tissue layer beneath the epithelium that helps to maintain and nourish the epithelium. It contains nerves, blood vessels, and immune cells.

Submucosa

This layer is not present in all areas of the mucous membranes in oral cavity. When present, it provides additional support and contains larger blood vessels, nerves, and occasionally glands.

Functions of the Permeability Barrier

The primary functions of the oral mucosa permeability barrier include:⁷

Protection

It serves as a physical barrier against mechanical insults, chemical irritants, and pathogens such as bacteria and viruses.

Selective Permeability

While protecting against harmful substances, it allows the selective passage of gases, nutrients, and fluids. This is essential for maintaining the internal atmosphere within the mouth.

 Sensory Functions

The oral mucosa contains numerous sensory receptors, including those for taste, touch, and temperature, which help in detecting changes in the oral environment.

Factors Affecting Permeability

Several factors can influence the permeability of the oral mucosa.⁸

Saliva

Saliva continuously bathes the oral mucosa, providing enzymes and immunological factors that protect against pathogens and aid in digestion. It also helps in maintaining the hydration and pH of the oral cavity.

 Cellular Composition

The density and type of cells in the epithelium (keratinized vs. non-keratinized) affect how substances penetrate the mucosa. Keratinized areas are generally less permeable than non-keratinized areas.

Mucosal Health

Conditions like inflammation, infection, or trauma can disrupt the structure of the mucosal barrier, altering its permeability

 Clinical Significance

The integrity of the oral mucosa permeability barrier is essential for overall oral health. Disruptions in this barrier can lead to several issues.

 Increased Susceptibility to Infections

Disruptions in the barrier can allow pathogens to penetrate, increasing the risk of infections.

Drug Delivery

Understanding the permeability of the oral mucosa is critical for the development of oral drug delivery systems (DDS). For instance, sublingual tablets and buccal patches rely on the permeability characteristics of the mucous membrane for drug absorption.

 Systemic Health

Certain systemic diseases, like diabetes or immune deficiencies, can manifest symptoms in the oral mucosa, indicating changes in its barrier properties.

The permeability barrier of the oral mucosa is a dynamic interface that not only protects the body from external threats but also facilitates the selective exchange of substances necessary for oral and systemic health. Its study and understanding are vital in fields ranging from dentistry and oral surgery to pharmacology and nutrition.

 Mechanism of Buccal Drug Absorption

Direct Absorption into Systemic Circulation

 Drugs administered buccally are absorbed via the mucosal lining of the mouth. The buccal mucosa is relatively permeable and contains a dense network of blood vessels. Following placement against the buccal mucosa, the drugs diffuse through the epithelial cells and directly enter the systemic circulation, bypassing the liver. This avoids first-pass metabolism, which is the chemical degradation of a drug in the liver, leading to a higher bioavailability compared to oral ingestion.⁹

Transcellular and Paracellular Pathways

Transcellular Absorption

Drugs can be absorbed by passing through the cells of the mucosal membrane. This pathway is typical for lipophilic (fat-soluble) drugs that can readily permeate cell membranes.

Paracellular Absorption

Hydrophilic (water-soluble) drugs and larger molecules might pass between the cells of the mucosal lining. This pathway is less common for buccal delivery due to the tight cell-to-cell junctions that restrict the movement of large or hydrophilic molecules.

A schematic depiction of the buccal and sublingual areas in the oral cavity is shown in Figure 1.¹⁰There is minimal enzymatic activity and a relatively neutral pH in the mouth cavity, which ranges from about 6.2 to 7.4. The oral mucosa has a limited surface area (100 200 cm²), but the buccal and sublingual regions have comparatively large areas (26.5±4.2 cm2 and 50.2±2.9 cm², respectively).^20,21An oral cavity's non-keratinized, stratified squamous epithelium lines the sublingual and buccal areas, with the former measuring 100-200 μm and 8-12 cells thick, and the latter 500-800 μm and 40-50 cells thick. Saliva components also attach to the buccal and sublingual epithelial surfaces, forming a mucus layer that is typically 70-100 μm thick.²² The connective tissue lamina propria and submucosa, which lie beneath the epithelium, include a network of lymphatic vessels, smooth muscles, and blood vessels. By passing through the superior vena cava, drugs can be absorbed directly into the systemic circulation through venous drainage.

Factors Influencing Buccal Drug Absorption

Physicochemical Properties of the Drug

Lipophilicity

More lipophilic drugs are typically absorbed more efficiently through BDDS, as they can readily diffuse through the lipid bilayers of the cell membranes.

Molecular Size

Smaller molecules are absorbed more readily than larger molecules, which may have difficulty penetrating the mucosal barrier.¹¹

Formulation Factors

pH and Ionic State

Salivary pH and the pKa influence the ionization state of the drug, affecting its solubility and absorption.

 Mucoadhesive Properties

Formulations that include mucoadhesive polymers (such as Chitosan, Hydroxypropyl methylcellulose, or Carbopol) can enhance the contact time of the drug with the mucosal surface, improving absorption.

Viscosity

Higher viscosity formulations may enhance the duration of drug retention within the buccal cavity, allowing more time for absorption.¹¹

Biological Factors

Condition of Buccal Mucosa

The health and integrity of the buccal mucosa play a critical role. Any damage or disease affecting the mucosal lining can impact drug absorption.

Saliva Flow

Excessive saliva can dilute the drug and wash it away from the absorption site, while dry mouth can hinder drug dissolution and reduce absorption.

Patient Factors

Factors such as age, gender, and individual variability can influence the characteristics of the mucosal lining and the vascular architecture, thereby affecting drug absorption.¹¹

Understanding the absorption kinetics and the influencing factors in BDD is crucial for optimizing the effectiveness of this route. The ability to bypass the GI tract and avoid f irst-pass metabolism makes buccal delivery particularly suitable for drugs that are sensitive to enzymatic degradation or have low oral bioavailability. As research advances, new formulations and technologies are continually being developed to enhance the efficacy of drug delivery through this promising route.¹¹

Uses of BDD

BDD is a sophisticated method of administering drugs through the buccal mucosa (the lining of the cheek),offering distinct advantages over conventional oral drug delivery. This route is particularly advantageous for drugs intended for immediate action or those that are extensively metabolized in the liver. Below, we discuss the specific uses and advantages of BDD, and provide examples of drugs commonly delivered through this route.¹⁰ Further, Table 1 shows the examples of drugs used in BDDS.

Systemic Drug Delivery

Administering drugs via buccal mucosa provides direct entry into the bloodstream, bypassing the digestive system and avoiding initial metabolism in the liver. This is especially beneficial for drugs that are not stable in the acidic environment of the stomach or are extensively metabolized by the liver.¹²

Local Therapy

Buccal delivery is also used for local effects, such as treating oral conditions (e.g., fungal infections or dental pain).^10-13

Advantages of BDD over Conventional Methods

Avoidance of First-Pass Metabolism

Drugs delivered buccally bypass the hepatic first pass effect, which can significantly increase their bioavailability compared to oral administration.

Rapid Onset of Action

BDD can provide a quicker onset of action than oral administration, which is critical for conditions that require rapid relief, such as pain or breakthrough seizures.

Improved Patient Compliance

Buccal formulations are often more convenient and easier to administer, especially for patients who have difficulty swallowing pills or for situations where water is not readily available.

Non-Invasive and Safe

Unlike injectables, buccal delivery is non-invasive, reducing the risk of infections and complications associated with injections.

Potential for Controlled Release

Advanced buccal formulations can be optimized to release a drug slowly and steadily, providing prolonged therapeutic effects.

Polymers in BDD

Polymers play a pivotal role in BDDS due to their ability to form bioadhesive films, enhance drug permeation, and control drug release.

The selection of the right polymer is essential for achieving optimal therapeutic outcomes. Here’s an overview of commonly used polymers in buccal drug delivery and their impact on the effectiveness of these systems.¹⁹

Key polymers employed in BDDS include Hydroxypro pyl methylcellulose (HPMC),Carboxymethyl cellulose (CMC), Chitosan, Carbopol, Sodium-Alginate, Xan than gums. Guar gums, Karaya gums, Polyacrylic acid (PAA), and Eudragit,among others.20-29 These polymers are chosen considering their biocompatibility, non-irri tating nature, and their ability to form films or gels that stick to the mucosal lining.

Mucoadhesive Polymers

Mucoadhesive polymers like Chitosan and PAA improve drug absorption and bioavailability by increasing mucosal contact time. These polymers interact with mucin, the glycoprotein present in the mucus, forming a strong yet reversible bond.

Controlled Release Polymers

Polymers like Eudragit and Ethyl cellulose are used to modulate the drug release profile, ensuring a sustained release that can be tailored according to therapeutic needs. Controlled release formulations are crucial in maintaining consistent plasma drug concentrations, reducing dosing frequency, and enhancing patient adherence.

Permeation Enhancers

Some polymers are included in buccal formulations to facilitate the permeation of drugs across the mucosal barrier. For example, cyclodextrins are used to increase the solubility and permeability of hydrophobic drugs.

Despite the advantages, buccal drug delivery faces challenges such as limited drug loading capacity, the variability of salivary flow, and the barrier properties of the mucosal membrane. Recent innovations aim to overcome these hurdles by employing nanotechnology, liposomes, and nanoparticles, which can improve drug stability and penetration.³⁰

Impact of Polymers on BDD

The polymer choice can significantly affect the DDS’s efficiency in several ways.^31,32

Enhanced Bioadhesion

Polymers like HPMC and Carbopol improve the adhesion of the DDS to the mucosal tissue, which is essential for effective drug absorption and extended release.

Controlled Release

Polymers can modulate the release rate of the drug, ensuring a constant drug concentration for optimal therapeutic effect over a prolonged period.

Increased Permeability

Some polymers, such as Chitosan, temporarily open the tight junctions between mucosal cells, enhancing the permeability of the buccal mucosa and allowing larger or more hydrophilic drugs to pass through more effectively.

Protective Barrier

Polymers can form a barrier that protects the active drug from enzymatic degradation in the oral cavity, improving the stability of the drug.

 Commonly Used Polymers in BDD

Hydroxypropyl Methylcellulose (HPMC)

HPMC plays a key role in BDDS due to its versatile properties, which include bioadhesion, film formation, and controlled release capabilities. This polymer is widely used in pharmaceutical formulations to improve the efficiency and effectiveness of drug delivery through the buccal mucosa.²⁰ Various grades of HPMC-such as HPMC K4M, HPMC K15M, HPMC K100M, and HPMC E5, are commonly used, along with other specific grades like HPMC E3, E50, and E4M.

Mucoadhesive Agent

HPMC can form hydrogen bonds with the mucin layer covering the buccal mucosa. This interaction enhances the adhesion of DDS to the mucosal surface, thereby increasing the duration of the drug in the buccal cavity. Further, extended residence time improves drug absorption and increases bioavailability, which is particularly beneficial for drugs that are poorly soluble or extensively metabolized in the GI tract.²⁰ 

Film Former

HPMC is an excellent film-forming polymer.It can be used to form thin, flexible, and uniform films that adhere to the mucosal tissues without causing irritation or discomfort. Films formed by HPMC can encapsulate the drug, protecting it from enzymatic degradation while providing a controlled release profile. This ensures a steady release of the drug, maintaining therapeutic levels for extended periods.³³

Viscosity Enhancer

In buccal formulations, HPMC can act as a thickening agent, increasing the viscosity of the formulation. Higher viscosity helps in maintaining the formulation in place against the buccal mucosa, reducing the risk of accidental swallowing and ensuring that the drug remains at the absorption site for a longer duration.³⁴

Controlled Release Matrix

HPMC can control the release rate of the drug through its hydrophilic matrix network. When hydrated, HPMC forms a gel that regulates the diffusion of the drug molecules. The controlled release matrix ensures a sustained drug release, which can help in reducing dosing frequency and improving patient compliance, particularly in chronic conditions.³⁵

Carbopol

Carbopol, also known as carbomer, is a synthetic polymer used extensively in pharmaceutical formulations due to its high viscosity, excellent thickening properties, and strong bioadhesive capabilities. Various grades of Carbopol are used, with Carbopol 934, 940, and 974P being commonly cited. Carbopol 934 and 940 are particularly known for their mucoadhesive properties, rendering them appropriate for buccal drug delivery systems. Carbopol 974P NF is also used in buccal applications, particularly for oral liquids and bioadhesive formulations. In the context of BDD, Carbopol plays a pivotal role due to these properties, significantly impacting the efficacy and delivery mechanism of buccal formulations.²³

Bioadhesive Properties

Carbopol exhibits strong mucoadhesive properties.It can interact with the mucin layer that coats the buccal mucosa, leading to prolonged adhesion of the DDS to the mucosal surface. The extended residence time of the drug formulation in the buccal cavity enhances drug absorption and increases bioavailability, particularly beneficial for drugs that degrade in the gastrointestinal tract or undergo extensive first-pass metabolism

Controlled Release Formulation

Carbopol forms hydrogels upon hydration, which can encapsulate active pharmaceutical ingredients. The cross-linked structure of these hydrogels controls the drug release rate from the formulation. Controlled re lease helps maintain a steady drug concentration in the plasma, improving therapeutic effectiveness and patient adherence through less frequent dosing.

Viscosity Modifier

Carbopol is used to adjust the viscosity of topical and mucosal formulations, including gels and ointments intended for buccal application. By enhancing the viscosity, Carbopol improves the manageability and ease of application of the drug formulation, ensuring that it remains in contact with the absorption site without spilling or migrating from the site of application.

Chitosan

Chitosan is a biocompatible, biodegradable polymer derived from the deacetylation of chitin, present in the exoskeleton of crustaceans such as crabs, shrimp, and lobsters. Due to its distinct characteristics, chitosan has garnered widespread attention in the field of buccal drug delivery.22 Here’s an overview of its role and impact in enhancing BDDS.

Mucoadhesive Propertie

Chitosan is renowned for its strong mucoadhesive characteristics. It adheres to mucosal surfaces by forming H-bonds and electrostatic interactions with the negatively charged mucosal cell surfaces. The enhanced adhesion results in increased residence time of the DDS at the site of application, leading to improved drug absorption and increased bioavailability. This proves highly favourable for drugs that are degraded in the GI tract or that require localized delivery at the mucosal surface.

 Enhancing Permeation

Chitosan has the ability to open tight junctions between epithelial cells temporarily. This function facilitates the paracellular transport of macromolecules. By enhancing the permeability of the buccal mucosa, chitosan allows for better absorption of larger or more hydrophilic drugs that otherwise struggle to permeate the mucosal barrier effectively.

Controlled Release Carrier

Chitosan can be used to formulate hydrogels and nanoparticles that encapsulate drugs, providing a controlled release matrix. Controlled release formulations help maintain a consistent drug concentration in the systemic circulation or at the site of action, reducing dosing frequency and improving patient compliance.²²

Protective Effects Besides its role in drug delivery, chitosan also offers protective effects against enzymes and pH changes in the oral cavity that could degrade the drug. This protective capability helps maintain the integrity and efficacy of the drug during the delivery process.²²

Chitosan's multifunctional capabilities make it extremely valuable in developing more effective BDDS. Its natural origin and biocompatibility also reduce the risk of toxicity and adverse reactions, making it suitable for long-term therapeutic applications.

Sodium Alginate

Sodium alginate is a naturally occurring biopolymer derived from brown seaweed that plays a critical role in BDDS. Its properties as a hydrophilic, gel-forming, biocompatible, and relatively inert material make it particularly suitable for pharmaceutical formulations intended for mucosal delivery.²⁴ Here’s an overview of the role and impact of sodium alginate in enhancing BDD.

Mucoadhesive Properties

Sodium alginate exhibits excellent mucoadhesive characteristics, which are crucial for BDD. When sodium alginate comes into contact with saliva, it undergoes gelation, forming a viscous gel that can adhere to the mucosal surfaces of the buccal cavity. This adhesion increases the residence time of the drug formulation on the buccal mucosa, which is essential for effective drug absorption and enhanced bioavailability, especially for drugs that are poorly absorbed through the GI tract or are subject to extensive first-pass metabolism.³⁶

Controlled Release Matrix

Sodium alginate can form hydrogels that encapsulate drugs, providing a matrix for controlled drug release. The rate of drug release from alginate matrices can be adjusted by altering the polymer concentration or by modifying the cross-linking density within the gel. Con trolled release is beneficial for maintaining therapeutic drug levels over extended periods, reducing the frequen cy of dosing and improving patient compliance.

Enhancement of Permeation

While alginate itself does not inherently enhance permeation, its formulation with permeation enhancers or in combination with other polymers can facilitate the transport of drugs across the buccal mucosa. This allows for the effective delivery of a broader range of drugs, including macromolecules that typically have poor mucosal permeability.

The use of sodium alginate in BDDS has a profound impact on the effectiveness of therapeutic interventions, providing a versatile platform for a variety of pharmaceutical applications. It is particularly valued in buccal formulations for its ability to form protective, mucoadhesive gels that enhance drug delivery and patient outcomes. Its ability to enhance drug bioavailability, protect active ingredients, and provide sustained release makes it an integral component in the evolution of BDD technologies.

Xanthan gums

Xanthan gum, a biopolymer derived from the bacterial coat of Xanthomonas campestris, is widely used in various industries, including food, cosmetics, and pharmaceuticals, due to its exceptional properties as a viscosity enhancer, stabilizer, and emulsifier. In the context of buccal drug delivery, xanthan gum plays a significant role due to its bioadhesive and gel-forming capabilities.³⁷

Mucoadhesive Properties

Xanthan gum can significantly augment the mucoadhe sive capabilities of BDDS. It forms a gel upon saliva exposure, which facilitates adhesion to the buccal cavity’s mucosal surfaces. The adhesion increases the residence time of the DDS at the site of application, improving the drug's absorption through the buccal mucosa, enhancing bioavailability, especially for drugs that are poorly absorbed through the GI tract or degrade in the GI environment.²⁵

Controlled Release Matrix

As a gel-forming agent, xanthan gum can encapsulate active ingredients, providing a matrix for controlled drug release. This gel matrix moderates the drug release rate from the formulation. Controlled release is beneficial for maintaining therapeutic drug levels over extended periods, reducing dosing frequency and improving patient compliance.

Viscosity Modifier

Xanthan gum is used to adjust the viscosity of formulations, which is crucial for ensuring that the DDS is manageable and remains in place once applied to the buccal mucosa. By optimizing viscosity, xanthan gum helps maintain the formulation at the site of application without significant dilution by saliva, thereby ensuring effective drug delivery and absorption.³⁸

Protective Barrier Formation

Beyond its role in drug release and adhesion, xanthan gum can form a protective barrier over the mucosa. This barrier can protect the mucosa from potential irritants and also shield the drug from degradation. This protective capability contributes to the overall effectiveness of the DDS, enhancing patient comfort and therapeutic outcomes.

The incorporation of xanthan gum into BDDS significantly impacts the effectiveness of therapeutic interventions. It not only improves the mechanical properties of formulations but also optimizes the release profiles and bioadhesive characteristics, making it a highly valuable component while developing advanced BDD technologies.

Guar gums

Guar gum, derived from the seeds of the Guar plant (Cyamopsis tetragonoloba), is a natural polysaccharide that is extensively used in the food and pharmaceutical industries due to its thickening, stabilizing, and emulsifying properties. In the context of BDD, guar gum plays a significant role, primarily due to its bioadhesive and controlled-release properties.²⁶

Bioadhesive Properties

Guar gum exhibits excellent bioadhesive properties, allowing it to adhere to the wet mucosal surfaces of the buccal cavity. This adhesion is facilitated by the swelling of guar gum particles when in contact with moisture, forming a gel-like substance that can bind to the mucosa. The increased residence time of the drug formulation on the mucosal surface enhances the absorption of the drug, improving its bioavailability and ensuring more effective drug delivery, particularly for drugs that degrade in the GI tract or undergo significant first-pass metabolism.³⁹

Controlled Release Matrix

Guar gum can be used to form hydrogels that encapsulate drugs, providing a matrix for controlled drug release. The rate at which the drug is released from such a matrix can be controlled by altering the cross-linking density and the concentration of guar gum. This controlled release mechanism ensures a sustained delivery of the drug, maintaining therapeutic levels over extended periods and reducing dosing frequency, which can significantly improve patient compliance.²⁶

Viscosity Enhancer

Guar gum is effective at increasing the viscosity of formulations, which helps in stabilizing the DDS once applied to the buccal mucosa. By enhancing the viscosity, guar gum ensures that the formulation remains in place at the site of application, reducing the risk of being washed away by saliva, thus enhancing the efficiency of drug absorption.⁴⁰

Protective Barrier Formation

The gel formed by guar gum not only aids in drug release but also acts as a protective barrier that shields the mucosal tissue from irritants and protects the drug from enzymatic degradation. This barrier function contributes to patient comfort and prolongs the effectiveness of the drug, enhancing the overall therapeutic outcomes.⁴¹

The utilization of guar gum in BDDS is a testament to the versatility and effectiveness of natural polymers in pharmaceutical applications. As research continues to evolve, further innovations in guar gum formulations are expected to optimize and expand its use in delivering therapeutic agents more efficiently through the buccal route.

Karaya gums

Karaya gum, sourced from the trees of the genus Sterculia, is a natural polysaccharide gum that has been used in various pharmaceutical applications due to its high molecular weight and excellent mucoadhesive properties. In BDD, karaya gum plays a significant role due to its unique characteristics that facilitate effective drug administration through the mucosal tissues.⁴²

Mucoadhesive Properties

Karaya gum is highly effective as a mucoadhesive agent due to its ability to swell upon contact with moisture and adhere strongly to the mucosal tissues of the buccal cavity. The strong mucoadhesion enhances the residence time of the drug formulation at the site of application, increasing drug absorption and improving bioavailability. This is particularly advantageous for drugs that require a prolonged presence at the site of action or for those susceptible to gastrointestinal degradation.⁴³

Controlled Release Capabilities

Karaya gum can form hydrogels that encapsulate active pharmaceutical ingredients, providing a matrix for controlled drug release. The porous structure of the hydrogel allows for the gradual diffusion of the drug into the buccal mucosa. This mechanism ensures a sustained release of the drug, which helps maintain a constant therapeutic level over extended periods, reducing the need for frequent dosing and thereby enhancing patient compliance.⁴⁴

Viscosity Enhancer

As a viscous gum, karaya helps increase the viscosity of the drug formulation, which aids in stabilizing the DDS once applied to the buccal mucosa. Increased viscosity prevents the drug formulation from being washed away by saliva, ensuring that the drug remains at the site of application for sufficient time to be absorbed effectively.⁴⁵

Karaya gum's impact on BDDS is profound, largely due to its natural origin, excellent bioadhesive and controlled release properties, and patient-friendly characteristics. The use of karaya gum in buccal formulations improves the therapeutic efficacy of drugs by optimizing their release profiles and ensuring sustained drug availability at the mucosal surface.

Conclusion

In conclusion, the application of polymers in BDD has significantly evolved, broadening the scope of pharmaceutical formulations and enhancing the efficacy and convenience of drug administration. Polymers have proven indispensable in the design of BDDS due to their unique properties which facilitate mucoadhesion, controlled release, and improved permeability. These characteristics ensure prolonged contact between the drug and the buccal mucosa for an extended period, enhancing the absorption and bioavailability of therapeutics, thus offering an advantageous alternative to traditional oral and injectable routes. The ability of polymers to form protective barriers limits the drug degradation and loss, while their biocompatibility minimizes the likelihood of adverse reactions, making BDDS particularly suitable for diverse patient populations, including those with swallowing difficulties or requiring quick therapeutic effects. The ongoing advancements in polymer science continue to unveil new polymer derivatives and composites that could further optimize the release profiles, adhesive properties, and patient compliance of buccal formulations. As research in this field progresses, it is anticipated that future studies will focus on the integration of innovative technologies such as nanotechnology and smart DDS to create more sophisticated BDD platforms. This integration will not only address current limitations but also expand the therapeutic potential of BDDS, potentially introducing personalized medicine applications that tailor treatments to individual patient needs based on specific biophysical markers. Therefore, the continued exploration and development of polymer-based BDDS hold the promise of transforming the landscape of pharmaceutical administration, making treatments more effective, less invasive, and more aligned with the needs and preferences of patients worldwide. The collaboration between material scientists, pharmacologists, and clinicians will be vital in advancing these technologies from the laboratory to clinical use, ensuring that they meet the stringent safety and efficacy standards required for medical applications.

Conflict of Interest

Nil