Buccal administration is atopicalroute of administration by whichdrugs held or applied in thebuccal (/ˈbʌkəl/) area (in thecheek) diffuse through theoral mucosa (tissues which line themouth) and enter directly into thebloodstream. Buccal administration may provide betterbioavailability of some drugs and a more rapidonset of action compared to oral administration because the medication does not pass through thedigestive system and thereby avoidsfirst pass metabolism.[1] Drug forms for buccal administration include tablets andthin films.
As of May 2014, the psychiatric drugasenapine; the opioid drugsbuprenorphine,naloxone, andfentanyl; the cardiovascular drugnitroglycerin; the nausea medicationprochlorperazine; the hormone replacement therapytestosterone; andnicotine as a smoking cessation aid were commercially available in buccal forms,[1] as wasmidazolam, ananticonvulsant, used to treat acuteepileptic seizures.[2]
Buccal administration ofvaccines has been studied, but there are challenges to this approach due toimmune tolerance mechanisms that prevent the body from overreacting toimmunogens encountered in the course of daily life.[3]
Buccal tablets are a type of soliddosage form administered orally in between the gums and the inner linings of the cheek.[4] Thesetablets, held within the buccal pouch, either act on theoral mucosa or are rapidly absorbed through the buccal mucosal membrane.[5] Since drugs "absorbed through the buccal mucosa bypass gastrointestinalenzymatic degradation and hepaticfirst-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 areunconscious,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 theparacellular pathway. Mosthydrophilic drugs permeate the cheek linings via the paracellular pathway through the mechanism ofpassive diffusion, andhydrophobic drugs are transported through thetranscellular pathway.[7] This route of administration is beneficial formucosal administration andtransmucosal 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 improvepatient 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.
Hydrocortisone is acorticosteroid that is clinically used to relieve the pain and discomfort ofmouth ulcers and functions to speed the healing of mouth ulcers.[citation needed] Common side effects include:oral thrush, visual disturbances (e.g.blurry vision), worsening ofdiabetes, worsening of mouthinfections, andallergic reactions (e.g. skin rash). Hydrocortisone is contraindicated in patientshypersensitive to hydrocortisone and those with mouth ulcers caused bydentures or infection as it can worsen the severity of mouth ulcers.
Some cautions and remarks include needing to gargle and spit water once tablet is fully dissolved to minimise risk of oral thrush, prolonged use may lead to withdrawal symptoms, chewing and swallowing of the tablet may limit its efficacy and give rise to additional side effects, and caution withCYP3A4inhibitors.
Fentanyl is anopioid analgesic used for the treatment ofbreakthrough pain incancer patients who are already receiving and/or are tolerant to maintenance opioid therapy for chronic cancer pain[10][11][12] Common side effects include:nausea,vomiting,headache,constipation anddrowsiness. Fentanyl is contraindicated in patients hypersensitive to fentanyl, opioid non-tolerant patients, management of acute orpostoperative pain, and those with severehypotension or severe obstructive airway diseases (e.g.COPD)
Some cautions include needing to keep tablets out of the sight and reach of children, and must not be sucked, chewed or swallowed. Other remarks include caution when administered in patients withhepatic or renal impairment, having drug interactions with CYP3A4 inducers and inhibitors and co-administration with CNSsedative agents (e.g.antihistamines) will increase CNS side effects.
Prochlorperazine maleate is under the class ofantiemetics andantipsychotics. These buccal tablets are administered for the treatment of severe nausea and vomiting associated withmigraine,[13][14] as well as managed in symptoms ofschizophrenia. Side effects typically seen in patients using prochlorperazine maleate tablets include drowsiness, blurred vision,dry mouth, and headache. In rare cases, these tablets may cause serious allergic reactions (i.e.anaphylaxis). Prochlorperazine maleate is contraindicated in certain patient groups, including hypersensitivity to prochlorperazine maleate, certain diseases likeglaucoma,epilepsy andParkinson's disease. They are also avoided in those with hepatic andprostate gland problems.
Special caution is taken in patients with high risk ofblood clot andstroke, along with associated risk factors (e.g.high blood pressure andhigh cholesterol levels). Those taking prochlorperazine maleate should avoid exposure to direct sunlight due tophotosensitivity and taken certain drugs that are either sedative and give dry mouth (e.g.anticholinergics) or target the heart (e.g.antihypertensives andanticoagulants). Other remarks include being most effective when taken after food and possible withdrawal symptoms if they are abruptly stopped.
The buccal mucosa, along with the gingival and sublingual mucosa, is part of theoral 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 ofdesmosomes,gap junctions andhemidesmosomes.[7] While it has a lesspermeable effect thansublingual administration, buccal administration is still capable of creating local orsystemic effects following drug administration.[7] In the oral cavity, buccal tablets potentiate their effect by entering the bloodstream direction through theinternal jugular vein into thesuperior vena cava,[8] avoiding acidichydrolysis to take place in thegastrointestinal tract.[16]
There are two major routes for drug transportation through the buccal mucosa: transcellular and paracellular pathways.[8]
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 eitherfacilitated diffusion for polar orionic compounds,diffusion for low molecular weight molecules, ortranscytosis andendocytosis for macromolecules.[8] The physicochemical properties of the drug, for example, its oil/waterpartition coefficient,molecular weight, structural conformation, determines whether the molecules are transported through the transcellular pathway.[8]
As thecell membrane islipophilic, it is more difficult for drugs that are hydrophilic topermeate the membrane. Hence, theexcipients 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 extracellularamphiphilic lipid matrix proves to be a major barrier formacromolecular 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 offer many advantages over other solid dosage forms also intended for oral administration (e.g.enteric-coated tablets,chewable tablets, and capsules).
Buccal tablets can be considered in patients who experience difficulty in swallowing, since these tablets are absorbed into the blood stream between the gum and cheek.[17][4] Difficulty in swallowing can occur in all age groups, especially in young infants and the elderly community.[18] Buccal tablets are also used in unconscious patients.[citation needed] Additionally, in the case of accidental swallowing of a buccal tablet, adverse effects are minimal as most buccal drugs cannot survive hepatic first-pass metabolism.
Compared to orally ingested capsules and tablets, buccal tablets provide a more rapidonset of action because the oral mucosa is highly vascularised.[17][9] Buccal tablets are also used in emergency situations because they can exert their effects quickly.
Buccal tablets directly enter the systemic circulation, bypassing the gastrointestinal tract and first-pass metabolism in the liver.[6] As such, patients can take a reduced overall dose to minimise symptoms. In addition, buccal tablets can be removed if adverse reactions appear.
In general, many drugs are not suitable to be delivered via the buccal mucosa due to the small dose criteria. Buccal tablets are rarely used in healthcare settings due to unwanted properties that may limit patient compliance, for example, unpleasant taste and irritation of the oral mucosa.[19] These undesired characteristics may lead to accidental swallowing or involuntary expulsion of the buccal tablet. Buccal tablets are also not preferred for drugs that requireextended-release.[17]
Absorption of drugs via the buccal membrane may not be suitable for all patients. Due to possible undesirable side effects and loss of drug effectiveness, buccal tablets must not be crushed, chewed, or swallowed under any circumstances. As such, buccal tablets are not always appropriate for patients (e.g. individuals onenteral tube feeding). It is also noted that eating, drinking or smoking should be avoided until the buccal tablet is fully dissolved to prevent drug efficacy changes and concerns of choking.[20]
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 swollenpolymer,[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 theactive 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 thesolubility of drugs that are poorly absorbed.[7]
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