Buccal administration

Buccal tablets are a type of solid dosage form administered orally in between the gums and the inner linings of the cheek.[4] These tablets, held within the buccal pouch, either act on the oral mucosa or are rapidly absorbed through the buccal mucosal membrane.[5] Since drugs "absorbed through the buccal mucosa bypass gastrointestinal enzymatic degradation and hepatic first-pass effect",[6] prescribing buccal tablets is increasingly common among healthcare professionals.

Buccal tablets serve as an alternative drug delivery in patients where compliance is a known issue, including those who are unconscious, nauseated, or having difficulty in swallowing (i.e. dysphagia).[7] A wide variety of these drugs are available on the market to be prescribed in hospitals and other healthcare settings, including common examples like Corlan®, Fentora®, and Buccastem®.

The most common route for drug transport through the buccal mucosa is the paracellular pathway. Most hydrophilic drugs permeate the cheek linings via the paracellular pathway through the mechanism of passive diffusion, and hydrophobic drugs are transported through the transcellular pathway.[7] This route of administration is beneficial for mucosal administration and transmucosal administration.[8] Buccal tablets are typically formulated through the direct compression of drug, powder mixture, swollen polymer, and other agents that assist in processing.[8]

Buccal tablets offer many advantages in terms of accessibility, ease of administration and withdrawal, and hence may improve patient compliance.[9] Notable drawbacks of buccal tablets include the hazard of choking by involuntarily swallowing the tablet and irritation of the gums.[7] Caution should be exercised along with counselling from medical practitioners before use of these tablets.

With recent advances on buccal tablets and in conditions where the conventional oral route (i.e. swallowing of tablet) cannot be delivered effectively, some commonly prescribed buccal tablets available in healthcare settings are listed below as examples.

A figure illustrating the cross-sectional area of the buccal mucosa.

The buccal mucosa, along with the gingival and sublingual mucosa, is part of the oral mucosa.[15] It is composed of non-keratinised tissue. Unlike intestinal and nasal mucosae, it lacks tight junctions and is instead equipped with loose intercellular links of desmosomes, gap junctions and hemidesmosomes.[7] While it has a less permeable effect than sublingual administration, buccal administration is still capable of creating local or systemic effects following drug administration.[7] In the oral cavity, buccal tablets potentiate their effect by entering the bloodstream direction through the internal jugular vein into the superior vena cava,[8] avoiding acidic hydrolysis to take place in the gastrointestinal tract.[16]

There are two major routes for drug transportation through the buccal mucosa: transcellular and paracellular pathways.[8]

A schematic diagram illustrating the penetration pathway for buccal drug delivery.

Small hydrophobic molecules and other lipophilic compounds mostly move across the buccal mucosa via the transcellular pathway. Drugs are transferred via the transcellular pathway through either facilitated diffusion for polar or ionic compounds, diffusion for low molecular weight molecules, or transcytosis and endocytosis for macromolecules.[8] The physicochemical properties of the drug, for example, its oil/water partition coefficient, molecular weight, structural conformation, determines whether the molecules are transported through the transcellular pathway.[8]

As the cell membrane is lipophilic, it is more difficult for drugs that are hydrophilic to permeate the membrane. Hence, the excipients of the formulation and the phospholipid bilayer assist in enhancing the diffusion of hydrophilic compounds (i.e. peptides, proteins, macromolecules).[8]

Generally, small low-molecular-weight hydrophilic compounds diffuse across the buccal epithelium through the paracellular pathway via passive diffusion. The extracellular amphiphilic lipid matrix proves to be a major barrier for macromolecular hydrophilic compounds.[8] After the administration of the buccal tablet, it must transport either through the epithelial layers to achieve its effect on the systemic circulation (systemic effect) or remain at a target site to elicit a local effect.[8]

Buccal tablets are dry formulations that attain bioadhesion through dehydrating local mucosal surfaces.[7] Many bioadhesive buccal tablet formulations are created through the direct compression method with a release retardant and swollen polymer,[8] and are designed to either release the drug in a unidirectional or multidirectional manner into the saliva.[7]

Conventional dosage forms are unable to ensure therapeutic drug levels in the circulation and the mucosa for mucosal and transmucosal administration because of the washing effect of saliva, and the mechanical stress of the oral cavity.[7] These two mechanisms act as a physiological removal system that removes the formulation from the mucosa, resulting in a decreased exposure time and unpredictable pharmacological profile of the drug's distribution.[7]

This effect can be countered by prolonging the contact between the active substance from the buccal tablet and the mucosa, the tablet should contain: mucoadhesive agents, penetration enhancers, enzyme inhibitors and solubility modifiers.[7]

The mucoadhesive agents assist in the maintenance of prolonged contact between the drug with the absorption site.[7] Penetration enhancers improve the ability of the drug to permeate the mucosa for transmucosal delivery or penetrate into the layers of the epithelium for mucosal delivery. Enzyme inhibitors partake in the protection of the drug from mucosal enzyme degradation, and solubility modifiers increase the solubility of drugs that are poorly absorbed.[7]

• Sublabial administration
• Sublingual administration
• Route of administration
• Pharmacology

• Generex Buccal Morphine and Fentanyl research