Article Type : Research Article
Authors : Mubarak ZO and Hameed F
Keywords : Buccal drug delivery system; BDDS, NDDS; Transmucosal drug delivery
Since the medication does not pass through the digestive system and therefore avoids the first-pass metabolism, buccal administration can provide better bioavailability and a faster onset of action for certain drugs as compared to oral administration. Buccal administration is a topical route of administration in which medications applied or retained in the buccal region (in the cheek) diffuse through the oral mucosa (tissues that line the mouth) and reach the bloodstream directly. Since the medication does not pass through the digestive system and therefore avoids the first-pass metabolism, buccal administration can provide better bioavailability and a faster onset of action for certain drugs as compared to oral administration. The present review presents various advantages, disadvantages, optimization, criteria for drug selection. The anatomy and physiology of buccal, dosage forms, factors affecting the absorption of drug from buccal cavity, absorption barriers, applications absorption enhancers and evaluation. This review also presents polymers in the buccal route of drug delivery.
The
buccal formulation is used to treat both local and systemic issues in the
mouth, specifically between the upper gums and the cheek. Buccal mucosa lines
the inner cheek and is used to treat local and systemic conditions in the mouth
between the upper gums and cheek. Buccal drug delivery has higher patient
acceptability than other non-oral routes of drug administration because it is
more vascularized and easier to administer and remove dosage. In the harsh
gastrointestinal environment, using the buccal route would result in extensive
first-pass metabolism and drug degradation [1,2]. Passive diffusion into the
lipoidal membrane is the primary mode of drug absorption through the buccal
mucosa. After absorption, the drug is transported to the jugular vein, which
then drains into the circulation, bypassing the liver and avoiding first-pass
metabolism. Large, hydrophilic, and unstable proteins, oligonucleotides, and polysaccharides,
as well as conventional small drug molecules, can be delivered via the buccal
route. Buccal drug delivery is the administration of medication through the
buccal mucosa of the oral cavity. The medication is placed between the gums and
the cheek during buccal administration. Medications in the form of pills,
films, or sprays are available, 1-3 cm2 in size. It is recommended
that you take 25 mg or less per day. Buccal delivery distribution takes 4-6
hours at the most [3,4] (Figure 1-3).
Advantages
Figure 1: The buccal area is the inner lining of the cheek and
lip, representing about one third of the surface area of the oral cavity.
Figure 2: Anatomy of
oral cavity.
Figure 3: Drug
transport across the mucosa can be transcellular or paracellular.
Limitations
Ideal Characteristics of Buccal Adhesive
Drug Delivery System
Uses of Buccal Delivery
Anatomy of Oral Mucosa
A layered squamous epithelium and a thicker lamina
propria make up the oral mucosa. The stratum basale (base layer), stratum
spinosum (prickle layer), stratum granulosum (granular layer), and stratum corneum
(corneum layer) are the four layers that make up the epithelium of keratinized
oral mucosa (keratinized layer). The two deep layers (basale and spinosum)
remain the same in the nonkeratinized epithelium, but the outer layers are
referred to as the intermediate and superficial layers. Depending on the area,
the mouth epithelium may be nonkeratinized or keratinized. Nonkeratinized
squamous epithelium covers the soft palate, inner lips, inner cheeks, the floor
of the mouth, and the ventral surface of the tongue (Figure 2). Keratinized
squamous epithelium can be found on the gingiva and hard palate, as well as
parts of the tongue's dorsal surface [4,5]. Keratinocytes in the stratum
granulosum divide into nonvital surface cells or squamous cells, resulting in
the stratum corneum. As they move from the stratum basale, where progenitor
cells are found, to the superficial surface, the cells terminally
differentiate. Nonkeratinized epithelium, unlike keratinized epithelium, does
not have keratinized superficial layers. In response to frictional or chemical
trauma, the nonkeratinized epithelium can easily transform into keratinizing
epithelium, resulting in hyperkeratinization. When the linea Alba appears, a
white ridge of calloused tissue that extends horizontally at the stage where
the maxillary and mandibular teeth come together and occlude, the buccal
becomes hyperkeratinized. The tissue has all of the layers of orthokeratinized
tissue, including the granular and keratin layers, and there is an abundance of
keratin on the tissue's surface. Patients who clench or grit their teeth
(bruxism) have a wider region of the buccal mucosa that becomes hyper
keratinized than just the linea alba. This larger white, rough, raised lesion
should be documented to account for the patient's parafunctional behavior in
the dental care plan [6,7] (Figure 4).
Functions of Oral Mucosa
Actions like eating, drinking, and talking constantly
put mechanical stress on the oral environment. Since the mouth is subjected to
rapid changes in temperature and pH, it must be able to adapt rapidly. The only
part of the body where taste can be detected in the mouth. The oral mucosa must
perform a variety of functions as a result of its particular physiological
characteristics. Protecting the underlying tissues from mechanical pressures,
bacteria, and toxins in the mouth is one of the most essential functions of the
oral mucosa. The hard palate and gingivae are closely bound by keratinized
masticatory mucosa. It makes up one-quarter of all oral mucosa. It protects the
underlying tissues by withstanding the loading forces of mastication. When
chewing and talking, the mucosa covering the cheeks, lips, and mouth floor
shifts to make room. It allows food to quickly move through the mouth during
mastication while shielding the underlying tissues from trauma. It accounts for
60% of the oral mucosa [8,9]. Saliva is the most important secretion of the
oral mucosa. Lubrication, pH buffering, and immunity are only a few of their
functions. Saliva's lubricating and antimicrobial functions are primarily
preserved by resting; saliva produces a flushing effect and aids in the removal
of oral debris and noxious Saliva contains a variety of antimicrobial proteins
that aid in the protection of the oral ecosystem against infectious agents.
Salivary lysozyme, lactoferrin, salivary peroxidase, myeloperoxidase, and
thiocyanate concentrations function as a defense mechanism. Three pairs of
major salivary glands (parotid, submandibular, and sublingual) and several
minor salivary glands produce saliva. It also helps in chemical digestion
because it includes the enzyme amylase, which breaks down carbohydrates into
sugars [9,10]. Sensation - The oral mucosa is highly sensitive to pain, touch,
temperature, and taste because it is densely innervated. The trigeminal (V),
facial (VII), glossopharyngeal (IX), and Vagus nerves are among the cranial
nerves involved in mouth sensations (X). Specialized mucosa surrounds the
dorsum of the tongue. It makes up about 15% of your oral mucosa and is made up
of taste buds that allow you to taste stuff [9]. Swallowing, gagging, and
hunger are all mouth-related reflexes. While not as important in humans, some
animals, such as dogs, rely on panting to control their temperature because
sweat glands are only found in their paws [9,11].
Environment of Buccal Mucosa
The oral cavity is distinguished by the presence of saliva, which is an intercellular ground fluid that covers the cells of the oral epithelia and is supplied by the salivary glands. The primary and minor salivary glands secrete mucus, which is contained in saliva [12].
Figure 4: Schematic illustration of the layers found in keratinized oral mucosa that include a deeper lamina propria and basement membrane in-between and superficial layers of strafied squamous epithelium that include from deepest to most superficial: 1: Stratum basale, 2: Stratum spinosum, 3: Stratum granulosum, 4: Stratum corneum
Role of Saliva
Role of Mucus
Design of Buccal Dosage Form [14] (Figure
5)
Matrix type: A Buccal patch with a matrix structure contains a combination of drug, adhesive, and additives. Bidirectional patches deliver the medication to the mucosa and the mouth [14] (Figure 5). Drug + Mucoadhesive Matrix
Figure 5: Design of buccal mucoadhesive dosage forms.
Figure
6:
Mucoadhesive Buccal Tablets.
Reservoir
type: A reservoir device buccal patch has a
cavity for the medication and additives that is separate from the adhesive.
Impermeable backing is used to guide the course of drug delivery, avoid drug
loss, and minimize patch deformation and disintegration when in the mouth.
Buccal Drug Delivery and Mucoadhesivity
The device's mucoadhesion is important. Mucoadhesive
materials bind to the mucin layer of a biological membrane to achieve systemic
drug delivery and include tablets, patches, tapes, films, semi-solids, and
powders [15].
Types of Buccal Mucoadhesive Dosage Forms
[16]
Based
on their geometry, there are three distinct groups.
Type - l
(Multidirectional)
Type - 2 (Bi-layered)
Type - 3 (Unidirectional)
Buccal Formulation
Buccal mucoadhesive tablets allow for drinking and
speaking without causing severe pain, unlike conventional tablets. They soften,
bind to the mucosa, and remain in place until full dissolution and/or release.
These tablets may be used to treat the palate, the mucosa lining the jaw, and
the region between the lip and the gum [17,18] (Figure 6).
Buccal Tablets
Buccal Patch/Film
Buccal Gel/Ointment
Evaluation of Buccal Tablets [19-21]
List of Drugs Delivered via Buccal Route
Acyclovir, Carbamazepine, Cetyl Pyridinium Chloride,
Chitosan, Chlorpheniramine maleate, Chlorhexidine diacetate, Diclofenac sodium,
Diltiazem Hydrochloride, Glucagon-like peptide (GLP)-1, Ergotamine tartrate,
Flurbiprofen, Fluoride, Melatonin, Metronidazole, Morphine sulphate Nalbuphine,
Nicotine, Nifedipine, Omeprazole, Piroxicam, Pindolol, Propranolol, Propolis,
Rh EFG (Recombinant human epidermal growth factor), Sodium fluoride, Salmon
calcitonin [22].
Product
Buccal drug delivery is a non-invasive option for
potent peptides and potential protein drug molecules, as well as systemic
delivery of drugs that are ineffective when taken orally. We conclude that it
is critical to not only create new drugs but also to refine the various routes
of administration to maximize efficiency while minimizing side effects. The
buccal mucosa has several benefits when it comes to managed drug delivery over
long periods of time. The first-pass metabolism in the liver and pre-systemic
clearance in the gastrointestinal tract are avoided since the mucosa is well
supplied with both vascular and lymphatic drainage.