Drug Delivery System for Buccal Administration

Buccal cavity definition

The buccal cavity is the part of the inner wall of the mouth that is located between the teeth and the buccal muscle. The buccal mucosa is a component of the oral mucosa that covers the inner surface of the cheek. This part of the mucosa is relatively smooth and does not have papillae like the tongue or hard palate. The buccal mucosa is mainly composed of multiple layers of flat squamous epithelial cells, and underneath is a layer of connective tissue, the lamina propria. This structure allows the drug to be absorbed through the mucous membrane. The thickness of the buccal mucosa is about 500-800 microns, while other areas such as the hard and soft palate, the floor of the mouth, the abdominal surface of the tongue, and the gums are thinner, about 100-200 microns. The permeability of the buccal mucosa is between the skin and the intestinal mucosa, and is 4-4000 times higher than that of the skin. The buccal mucosa is rich in blood vessels, which help drugs to be quickly absorbed into the bloodstream.

Structure of buccal mucosa. (Patel, A. S., 2020)

Buccal drug delivery system

Buccal mucosa is the target site of buccal drug delivery system. These systems are designed to absorb drugs directly from mucosal surfaces into the bloodstream, avoiding first-pass effects and potential drug degradation in the digestive tract. Buccal mucosal delivery, as a non-invasive drug delivery route, is particularly suitable for the delivery of peptide and protein drugs, as well as those that are not effective orally. Buccal drug delivery systems include a variety of dosage forms designed to deliver drugs through the buccal mucosa. These dosage forms include buccal tablets, patches, films and gels. Buccal tablets can be single - or multilayer structures, made using bioadhesive polymers that can come into direct contact with the oral mucosa and dissolve or adhere. The buccal gel/ointment formulation has the advantage of rapidly dispersing in the oral mucosa and can solve the problem of continuous release of the drug by using a bioadhesive formulation. Buccal patch and film dosage forms typically contain an impermeable backing layer to prevent drug leakage, reduce deformation, and control the direction of drug release.

Advantages of buccal drug delivery system

The drug is easy to administer and treatment can be stopped quickly in an emergency.

Long-term release of the drug can be achieved.

For unconscious or traumatized patients.

Bypassing the liver's first-pass metabolism, it has a high bioavailability.

This is especially true for drugs that are unstable in an acidic environment.

Drug absorption occurs through passive diffusion.

Due to the close contact with the surface of the absorption film, the absorption rate is high.

The effect is rapid.

Limitations of buccal drug delivery system

It cannot be used for drugs that are unstable at buccal mucosal pH.

Do not apply to drugs that have an unpleasant taste, bitter or disgusting smell, or drugs that may cause irritation.

It should only be used in smaller doses.

Only for drugs that need to be absorbed by passive diffusion.

Food and drink should be avoided during administration.

Factors affecting buccal absorption

Membrane factors involve the degree of keratinization, the surface area available for absorption, the mucus layer of the salivary pellicle, intercellular lipids of the epithelium, basement membrane, and lamina propria. Besides, the absorptive membrane thickness, blood supply/ lymph drainage, cell renewal and enzyme content will all contribute to reducing the rate and amount of drug entering the systemic circulation.

Polymer-related factors include concentration, swelling, molecular weight, conformation, and flexibility of the polymer chain.

Environmental factors such as the pH of the polymer-substrate interface, functional strength, and initial contact time.

Physiological factors such as disease status and mucin turnover.

Formulation for buccal drug delivery system

When designing a buccal drug delivery system, the following aspects need to be considered:

Drug Substance: The drug should have a low conventional single dose. The biological half-life of the drug should ideally be between 2-8 hours. The drug should show variable or higher Tmax values when administered orally. The drug should exhibit first-pass metabolism or presystemic drug elimination when administered orally. The drug absorption should be passive when administered orally.

Bioadhesive polymers: Selection of suitable bioadhesive polymers that adhere effectively to the buccal mucosa. Polymers should form a stable bond with the mucosal surface to ensure prolonged contact time.

Backing membrane: Use of impermeable backing membranes to prevent the loss of drug and ensure good patient compliance. Materials such as magnesium stearate, HPC (hydroxypropyl cellulose), polycarbophil, HPMC (hydroxypropyl methylcellulose), CMC (carboxymethyl cellulose), and carbopol are commonly used.

Permeation enhancers: Agents that enhance the permeation of the drug through the buccal mucosa. The choice of permeation enhancer depends on the physicochemical properties of the drug, the nature of the vehicle, the site of administration, and other additives.

Buccal dosage form design: Matrix type-the buccal patch designed in a matrix configuration contains drug, adhesive, and additives mixed together.

Reservoir type-the buccal patch designed in a reservoir system contains a cavity for the drug and additives separate from the adhesive. An impermeable backing is applied to control the direction of drug delivery; to reduce patch deformation and disintegration while in the mouth, and to prevent drug loss.

Evaluation: Drug-excipient interaction studies using techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thin-layer chromatography. Physical evaluations including content uniformity, weight uniformity, and thickness uniformity.

Other tests include include measurement of residence time, permeation studies, swelling studies, release rate studies, toxicity and irritancy studies, quantification of bioadhesion, mechanical properties.

Mucoadhesive strength: Determined using a modified balance method with freshly excised buccal mucosa from animals like rabbits or sheep.

Mucoadhesive time: The time it takes for the tablet to detach from the buccal mucosa under simulated conditions.

Drug release: Studied using the USP XXIII rotating paddle method with a phosphate buffer at pH 6.8.

Drug permeation: Performed using a Franz-type diffusion cell with a phosphate buffer at pH 6.8 on the donor side and pH 7.4 on the receptor side.

Related drug formulation services at BOC Sciences

Buccal tablet

Buccal tablets are small, flat, and oval in shape with a diameter of approximately 5–8 mm. The direct compression technique is most widely used for the preparation of buccal tablets; other techniques like wet granulation can also be employed. These tablets stick to the buccal mucosa in the presence of saliva. They are designed to release the drug either unidirectional, targeting buccal mucosa or multidirectional into the saliva and not to disintegrate. It is placed near the opening of parotid duct to provide the medium to dissolve the tablet. Buccal tablets are most often used when replacement hormonal therapy is the goal. Long-Acting Buccal Tablets include use of viscous natural or synthetic gums or mixtures of gums can be compressed to form a hydrated surface layer from which the medicament slowly diffuses and is available for absorption through buccal mucosa.

Microspheres, microcapsules, microparticles: The local irritation caused by microspheres or microcapsules or microparticles at the site of adhesion is less and provides a comfortable sensation of a foreign object within the oral cavity.

Wafers: Wafer is a drug delivery system with surface layers possessing adhesive properties.

Lozenges: Bioadhesive lozenge offers prolonged drug release with improved patient compliance compared to Conventional lozenges, thus avoiding multiple daily doses.

Mucoadhesive buccal tablets. (Mishra, R., 2021)