Buccal administration
Buccal administration is a topical route of administration by which drugs held or applied in the buccal (/ˈbʌkəl/) area (in the cheek) diffuse through the oral mucosa (tissues which line the mouth) and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism.[1] Drug forms for buccal administration include tablets and thin films.
As of May 2014, the psychiatric drug asenapine; the opioid drugs buprenorphine, naloxone, and fentanyl; the cardiovascular drug nitroglycerin; the nausea medication prochlorperazine; the hormone replacement therapy testosterone; and nicotine as a smoking cessation aid were commercially available in buccal forms,[1] as was midazolam, an anticonvulsant, used to treat acute epileptic seizures.[2]
Buccal administration of vaccines has been studied, but there are challenges to this approach due to immune tolerance mechanisms that prevent the body from overreacting to immunogens encountered in the course of daily life.[3]
Tablets[edit]
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.
Benefits and limitations[edit]
Benefits[edit]
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. 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 rapid onset 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.
Limitations[edit]
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 require extended-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 on enteral 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]
Formulation and manufacturing[edit]
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]