WORLD

Islam et al. JOURNAL OFWorld

PHARMACY AND PHARMACEUTICAL
Journal of Pharmacy SCIENCES
and Pharmaceutical Sciences
SJIF Impact Factor 7.632

Volume 8, Issue 12, 77-93 Review Article ISSN 2278 – 4357

A COMPREHENSIVE REVIEW ON BUCCAL DRUG DELIVERY

SYSTEM

Fariya Mozammel, Irin Dewan, S. M. Ashraful Islam*

Department of Pharmacy, University of Asia Pacific, 74/A Green Road, Farmgate, Dhaka-
1205, Bangladesh.

INTRODUCTION
Article Received on
02 Oct. 2019, Drug administration through the mucosal membranes (buccal mucosa)
Revised on 23 Oct. 2019, is known as buccal drug delivery. It has been introduced in 1947 when
Accepted on 12 Nov. 2019
DOI: 10.20959/wjpps201912-14974 dental adhesive powder and gum tragacanth were mixed to apply
penicillin to the oral mucosa.[1] Oral route is perhaps the most preferred
by patients and clinicians alike among the various routes of drug
*Corresponding Author
Prof. Dr. S. M. Ashraful
delivery.[2] Fifty percent (50%) commercially available drugs are
Islam administered through oral drug delivery system and this system has
Department of Pharmacy, more advantages due to ease of administration and patient
University of Asia Pacific,
acceptance.[3] But certain drugs have lack of efficacy due to decreased
74/A Green Road, Farmgate,
GI intolerance, bioavailability, unpredictable absorption, pre-systemic
Dhaka-1205, Bangladesh.
elimination etc. In comparison to the conventional oral medications
retentive buccal mucoadhesive formulations may prove to be a viable alternative as they can
be readily attached to the oral mucosa (Figure 1-2), retained for a longer period of time and
can be removed at any time.[4]

Delivery of therapeutic agents via buccal drug delivery system has become highly interesting
for both local as well as systemic action. Bio adhesion is the basic process in buccal drug
delivery system. Bio adhesion is a phenomenon of interfacial molecular attractive forces
between the natural or synthetic polymers and the surfaces of biological substrate which
allows the polymer to adhere to mucosal surface for an extended or long period of time.

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Figure 1: Structure of the Human Oral Mucosa.

IMPORTANCE OF BUCCAL DRUG DELIVERY SYSTEM: Buccal drug delivery is

much more recent research subject then the other route for the past several years due to
advances of the biotechnology which introduces peptide drugs. These biomolecules cannot be
administered by oral route due to low absorption, degradation and low bioavailability. Here,
buccal process turns out to be more effective and acceptable. Buccal process is also more
effective and acceptable for short half-life drugs (e.g., midazolam) which are not suitable for
oral administration due to frequent administration. On the other hand, injectable preparations
of short half-life drugs result in poor patient compliance.

Figure 2: Anatomic Location and Extent of Masticatory, Lining and Specialized

Mucosa.

Large surface area represented by buccal mucosa (23% of the total surface of the oral mucosa
including the tongue) makes it more fit for systemic drug delivery (Figure 2). The buccal
cavity provides a highly vascular mucous membrane site for the administration of drug. In

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humans, the permeation of drugs through the buccal epithelium is said to associate both the
transcellular and paracellular routes.[5]

ADVANTAGES OF BUCCAL DRUG DELIVERY SYSTEM

1. Drug administration is easy and therapy extinction in emergency can be facilitated.
2. Drug can be administered in unconscious and trauma patients. Bioavailability increases
due to prevention of first pass metabolism.
3. Flexibility in physical state and flexible shape, size and surface of dosage form.
Absorption rate is maximum rate due to close contact with the absorbing membrane.
Onset of action is rapid.[6]
4. Mucosal surfaces do not have a stratum corneum in comparison to TDDS. So, the major
barrier layer to transdermal drug delivery is not a factor in buccal routes of
administration.[7-8]
5. Though less permeable than the sublingual area, the buccal mucosa is well vascularized,
and drugs can be rapidly absorbed into the venous system underneath the oral mucosa.
6. Dose reduction can be achieved, reduces dose dependent side effects, and eliminates peak
valley profile. Drugs unstable in acidic environment of stomach or are destroyed by the
enzymatic or alkaline environment of the intestine can be administered.
7. Improved patient compliance due to elimination of associated pain with injections.[8]

LIMITATIONS OF BUCCAL DRUG ADMINISTRATION

1. Ample dose are often difficult to be administered.
2. Patients have possibility to swallow the tablet being forgotten. Eating and drinking may
be restricted till the end of drug release.
3. Unacceptable for drugs, which are unstable at pH of buccal environment.[9]
4. Bitter taste and unpleasant drugs that irritate the mucosa cannot be administered by this
route.[10]
5. Continuous saliva secretion from the major and minor salivary glands leads to the rapid
dissolution of the drug.[11]
6. Formulation may get disrupted by the swelling and hydration of the bioadhesive polymers
due to over hydration of the formation.
7. Surface area available is less for absorption in comparision of oral route.[12]

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BUCCAL FORMULATIONS
1. Buccal mucoadhesive tablets: Buccal mucoadhesive tablets are dry dosage forms that
have to be moistened prior to placing in contact with buccal mucosa. Most commonly
investigated dosage form tablets are small, flat and oval with a diameter of approximately
5-8 mm. They may be prepared using different methods like as wet granulation technique
or direct compression.[13]
2. Semisolid preparations (Ointments and Gels): Compared to solid bioadhesive dosage
forms bioadhesive gels or ointments have less patient acceptability and most of them are
used within the oral cavity only for localized drug therapy. They have the advantage of
easy dispersion throughout the oral cavity.[8]
3. Patches and films: Patches are mainly laminates consisting of an impermeable backing
layer and drug-containing reservoir layer where drug is released in a controlled manner
from the drug-containing reservoir layer, and a bioadhesive surface for mucosal
attachment.[3] So they consists of two laminates, with an aqueous solution of the adhesive
polymer being cast onto an impermeable backing sheet, which is then cut into the
required oval shape.
A novel mucosal adhesive film called “Zilactin” - consisting of an alcoholic solution of
HPC and three organic acids which was applied to the oral mucosal can be retained in
place for at least 12 hrs. even when it is challenged with fluids.[8]
4. Microspheres, microcapsules, micro particles: They cause less local irritation and
provide comfortable sensation of a foreign object within the oral cavity.[3]
5. Powders: Powder containing HPC and beclomethasone when sprayed on to the oral
mucosa of rats, a significant increase in the residence time relative to an oral solution is
seen and 2.5% of beclomethasone is retained on buccal mucosa for over 4 hrs.[2]
6. Lozenges: They act typically within the mouth including the corticosteroids,
antimicrobials, local anaesthetics, antifungal and antibiotics.[13]
7. Bioadhesive liquids and Hollow fibers: Liquids used to coat buccal surface are viscous
and serve as either protective agents or as drug vehicles for delivery of drug on to the
mucosal surface. Dry mouth is treated with artificial saliva solution that is retained on
mucosal surfaces to provide lubrication. Burnside et al designed a micro porous hollow
fiber of poysulfone, intended for delivery of histrelin. This fiber is intended to be placed
in the buccal cavity for oral mucosal drug delivery.[3]
8. Buccal sprays: This type of spray delivers a mist of fine droplets onto mucosal
membrane layer. e. g. Estradiol sprays.[10]

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PRINCIPAL CONSTITUENTS OF BUCCAL DRUG DELIVERY SYSTEM

1. Drug component: The drug should have following characteristics:
 Small conventional single dose of the drug.
 For controlled drug delivery it should have biological half-life between 2-8 hrs.
 Drug absorption should be passive when given orally.
 Higher tmax values when given orally.
 Exhibits first pass effect.

2. Polymers (Bio-adhesive): In the formulation of buccoadhesive dosage forms the first step
is to select and characterize the appropriate bio-adhesive polymers. In matrix devices bio-
adhesive polymers are also used in which the drug is embedded in the polymer matrix
controlling the duration of release of drugs.
3. Backing membrane: Backing membrane material should be inert and impermeable both
to the drug and penetration enhancer so that it can prevent the drug loss and offers better
patient compliance. Some examples of backing membrane include HPMC, HPC,
polycarbophil.
4. Permeation Enhancers: Permeation enhancers are substances facilitating the permeation
through buccal mucosa. Selection of enhancer and its efficacy depends on the
physicochemical properties of the drug, site of administration, nature of the vehicle and other
excipients.[14]

MECHANISM OF MUCOADHESION
The adhesion mechanism of certain macro-molecules to the surface of a mucous tissue is not
well understood yet. Attraction and repulsion between polymer and mucus membrane are the
main forces for mucoadhesion. The attraction force must dominate for a successful
mucoadhesion. The mechanism of mucoadhesion is generally divided in two steps: contact
stage & consolidation stage. Each step can be facilitated by the nature of the dosage form and
its administration process.

From the figure (Figure 3) we can see that the first stage or the contact stage is characterized
by the contact between the mucous membrane and the mucoadhesive by means of spreading
and swelling of the formu-lation and thus initiating its deep contact with the mucus layer.
Again we can see in the consolidation step in presence of moisture the mucoadhe-sive
materials are activated.

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Figure 3: Mechanism of Mucoadhesion.

The mucoadhesive molecules become break free and link up by weak van der Waals and
hydrogen bonds in presence of moisture. Different enzymes responsible for hydrolysis like
pepsin, trypsin and chymotrypsin, makes the enzymatic activity of buccal mucosa [Carvalho
et al., 2010]. Different theories about the mucoaddition are as follows:
1. Electronic Theory: According to this theory, electronic transfer occurs upon contact of an
adhesive polymer and the mucus glycoprotein network. This is due to differences in their
electronic structure. This proposes to result in the formulation of an electronic double layer at
the interface.
2. Adsorption Theory: According to the adsorption theory, adhesive attachment occurs on
the basis of hydrogen bonding and Vanderwaal’s forces.[15]

Figure 4: The Process of Consolidation.

According to this theory (figure 4), after an initial contact between two surfaces, the materials
adhere because of surface forces acting between the atoms in the two surfaces.[13]
3. Wetting Theory: The wetting theory applies to liquid systems or low viscosity
bioadhesives which produce affinity to the surface in order to spread over it. This affinity can

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be measured by using measuring techniques for example contact angle which should be equal
or close to zero (Figure 5).[11] According to Dupres equation work of adhesion is given by:
Wa = YA + YB – YAB
Where A & B refer to the biological membranes and the bioadhesive formulation
respectively. The work of cohesion is given by: Wc = 2YA or YB.

Figure 5: The Wetting Theory.

For a bioadhesive material B spreading on a biologicalsubstrate, the spreading coefficient is

given by: SB/A = YA – (YB+YAB) should be positive for a bioadhesive material to adhere
to a biological membrane.[16]

4. Diffusion Theory: According to this theory, mucus and the polymer chains mix to a
sufficient depth to create an adhesive bond which is semi-permanent type where the
penetration depends on diffusion coefficient (Figure 6).

Figure 6: Secondary Interaction between Muco-adhesive device and Mucus.

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5. Fracture Theory: Fracture theory of adhesion is related force required to detach or

separate two surfaces after adhesion. The fracture strength is equivalent to adhesive strength
as given by, G = (Eε. /L) ½ (Figure 7).

Figure 7: Fractures Occurring for Mucoadhesion.

Where: E- Young’s modules of elasticit, ε- Fracture energy, L- Critical crack length when
two surfaces are separated.[11]

SOME FACTORS THAT AFFECTS MUCOADHESION IN THE ORAL CAVITY

A. Polymeric Factors
1. Molecular weight: In case of linear polymers bio-adhesiveness improves with increasing
molecular weight. For maximum mucoadhesion the optimum molecular weight
depends upon the tissue and the type of mucoadhesive polymer. Polymer with high
molecular weight promotes physical entangling where mucus layer is better penetrated by
the low molecular weight polymers. Higher molecular weight polymers will not moisten
quickly to expose free groups for interaction with the substrate. On the other hand low
molecular weight polymers will dissolve quickly.[17]
2. Active polymer concentration: This factor depends on type of dosage form. In case of
solid dosage form, the higher the concentration of polymer the stronger the
mucoadhesion. However, for liquid dosage form, maximum mucoadhesion is shown
when there is an optimum polymer concentration.[18] To produce maximum level of
bioadhesion there should be an optimum concentration of a bio adhesive polymer.
3. Polymer chain flexibility: It is important for interpenetration and enlargement. The
mobility of the individual polymer chain decreases upon cross linking of water soluble

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polymers and thus the effective length of the chain decreases that can penetrate into the
mucus layer and as a result bioadhesive strength is reduced.
4. Spatial Conformation: Spatial confirmation of a molecule is also an important factor.
Despite a high molecular weight of 19,500,000 for dextrans, they have similar adhesive
strength to the polyethylene glycol with a molecular weight of 200,000. The helical
conformation of dextran may shield many adhesively active groups, primarily responsible
for adhesion, unlike PEG polymers which have a linear conformation.
5. Cross-Linking Density: As the density of cross-linking increased, diffusion of water into
the polymer network occurs at a lower rate which in turn causes an insufficient swelling
of the polymer and a decreased rate of interpenetration between polymer and mucin.
Flory has reported this general property of polymers, in which the degree of swelling at
equilibrium has an opposite relationship with the degree of cross-linking of a polymer.
6. Hydrogen Bonding Capacity: It is another critical factor in polymeric mucoadhesion. It
was reported that for mucoadhesion to occur, desired polymers must have functional
groups and they have to form hydrogen bonds. It was also found that flexibility of the
polymer is important to improve this hydrogen bonding potential. Polymers such as poly
vinyl alcohol, hydroxylated methacrylate, and poly methacrylic acid, as well as all their
copolymers, have good hydrogen bonding capacity.
7. Charge sign of polymer: This is an important element for bioadhesion. In comparison to
anionic polymers, nonionic polymers undergo a smaller degree of adhesion. Peppas and
Buri have demonstrated that strong anionic charge on the polymer is one of the required
characteristics for mucoadhesion. Some cationic high-molecular-weight polymers, such
as chitosan, have shown to possess good adhesive properties specially in a neutral or
slightly alkaline medium.
8. Hydration (Swelling): Polymer swelling permits a mechanical entanglement by exposing
the bioadhesive sites for hydrogen bonding and/or electrostatic interaction between the
polymer and the mucous network. However, a critical degree of hydration of the
mucoadhesive polymer exists where optimum swelling and bio adhesion occurs.

B. Environment Related Factors

1. Applied Strength: Whatever the polymer the adhesion strength increases with the
applied strength or with the duration of its application. The pressure initially applied to
the mucoadhesive tissue contact site can affect the depth of interpenetration. If high

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pressure is applied for a sufficiently long period of time, polymers become mucoadhesive
even though they do not have attractive interaction with mucin.
2. pH: On the surface of both mucus and the polymers pH generally influences the charge.
Due to difference in dissociation of functional groups on the amino acids and the
carbohydrate moiety of the polypeptide backbone mucus will have a different charge
density depending on pH. It should be also noted that pH of the medium is important for
the degree of hydration of cross linked polyacrylic acid, showing consistently increased
hydration from pH 4 to 7 and then hydration decreases as the alkalinity increases.
3. Initial Contact Time: To determine the extent of swelling and interpenetration of the
bioadhesive polymer chains, the initial contact time between the bioadhesive and mucus
layer is important. Moreover, bioadhesive strength increases as the initial contact time
increases.[17]

C. Physiological Variables
1. Mucin Turnover: Mucin turnover is limits the residence time of the mucoadhesive on
the mucus layer. Due to mucin turnover mucoadhesives are detached from the surface
no matter how high the mucoadhesive strength is. Mucin turnover results in
substantial amounts of soluble mucin molecules. These molecules interact with the
mucoadhesive before they have a chance to interact with the mucus layer.
2. States of disease: The mucoadhesive property needs to be evaluated if they are used in
the diseased state. The physiochemical properties of mucus changes during disease
conditions such as bacterial and fungal infections, common cold etc.[8]

MECHANISM OF ABSORPTION BY BUCCAL CAVITY: Absorption of drug through

buccal cavity occurs by passive diffusion of the nonionized species through the intercellular
spaces of the epithelium using a concentration gradient. By first order kinetics the dynamics
of buccal absorption can be explained. There is a linear relationship between time and
salivary secretion which can be given as follows:
-dm/dt= KC/ViVt
Where, m - mass of drug in mouth at time, K - proportionality constant, C - concentration of
drug in mouth at time, Vi - the volume of solution put into mouth cavity and Vt - salivary
secretion rate [Reddy et al., 2013].

PATHWAYS FOR BUCCAL DRUG ABSORPTION: There is a passive pathway for

buccal drug to be transported via oral mucosa (Figure 8).

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Figure 8: Pathways of Buccul Drug Absorption.

There are two routes: paracellular routes / Intercellular routes and Transcellular routes
/Intracellular routes. One route is usually preferred over the other depending on the
physicochemical properties of the diffusant. Permeation by the transcellular route may
involve transport across the apical cell membrane, intracellular space and basolateral
membrane either by passive transport or by active transport. Substances with low molar
volume (80 cm3/mol) can be transported through aqueous pores in cell membranes of
epithelium. Cell membrane acts as the major transport barrier for hydrophilic compounds and
the intercellular spaces pose as the main barrier to permeation of lipophilic compounds. Due
to stratified oral epithelium, solute permeation requires combination of these two routes.[19]

SOME EXPERIMENTAL METHODOLOGY FOR BUCCAL PERMEATION

STUDIES
A. In vitro Methods: In vitro studies uses buccal tissues from animal models examining
drug transport across buccal mucosa where animals are sacrificed immediately before the
start of an experiment. Firstly buccal mucosa with underlying connective tissue from the
oral cavity is surgically removed. After the connective tissue is carefully removed, the
buccal mucosal membrane is isolated which are then placed and stored in ice-cold (4°C)
buffers (usually Krebs buffer) until mounted between side-by-side diffusion cells for the
in vitro permeation experiments.
B. In vivo Methods: By means of buccal absorption test this method was first originated by
Beckett and Triggs (Figure 9).

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Figure 9: In-vivo Drug Release Apparatus.

The kinetics of drug absorption was measured in this method. Followed by the expulsion of
the solution it involves the swirling of a 25 ml sample of the test solution for up to 15 minutes
by human volunteers. In order to assess the amount of drug absorbed the amount of drug
remaining in the expelled volume is then determined. Various modifications of the buccal
absorption test have been carried out correcting for salivary dilution and accidental
swallowing, but these modifications also suffer from the inability of site localization.

C. Experimental Animal Species: Another methodology is carried out in experimental

Animal Species. Special attention is warranted to the choice of experimental animal
species for such experiments aside from the specific methodology employed to study
buccal drug absorption/permeation characteristics. Many researchers have also used small
animals including rats and hamsters or permeability studies.[14]

BUCCAL PATCHES EVALUATION STUDIES

1. pH of surface: To investigate the possibility of any side effects in vivo the surface pH of
the buccal patch is determined. Firstly the buccal patches are left to swell by keeping it in
contact with 1 ml of distilled water for 2 hr at room temperature on the surface of an
agar plate. The surface pH is measured by means of a pH paper placed on the surface of
the swollen patch.[2]
2. Measurements of thickness: Using an electronic digital micrometer the thickness of
each film is measured at five different locations (centre and four corners).[20]
3. Folding Endurance: It is determined manually. Patch is repeatedly folded at same point
until it ruptures or breaks. Folding endurance of the patches is determined by repeatedly
folding one patch at the same place till it broke or folded up to 200 times manually which

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is considered satisfactory to reveal good patch properties. The number of folding required
for cracking or breaking a patch was taken as the folding endurance.
4. Swelling Study: Due to swelling weight increase. Buccal patches are weighed
individually (W1) and placed separately in 2% agar gel plates, incubated at 37°C ± 1°C
and examined for any physical changes. A graph paper is placed beneath the petridish, to
measure the increase in the area. After every interval of 3 hours, patches are removed
from the gel plates and using the filter paper excess surface water is removed carefully.
The swollen patches are then again weighed (W2) and using the following formula the
swelling index (SI) were calculated.
SI = {(W2-W1)/W1} X 100
The difference in the weights gives the weight increase due to absorption of water
and swelling of patch.
5. Study of thermal Analysis: Using differential scanning calorimeter (DSC) thermal
analysis study is performed.
6. Morphological Characteristics: Using scanning electron microscope (SEM)
morphological characters are studied by.
7. Test for water absorption capacity: Circular Patches, with a surface area of 2.3 cm2 are
allowed to swell on the surface of agar plates prepared in simulated saliva and kept in an
incubator maintained at 37°C ± 0.5°C. Samples are weighed at various time intervals
(0.25, 0.5, 1, 2, 3, and 4 hours) and then allowed to dry for 7 days in a desiccators over
anhydrous calcium chloride at room temperature then the final constant weights are
recorded.
Water Uptake (%) = {(Ww – Wf)/ Wf } X 100
Where, Ww is the wet weight and Wf is the final weight. The swelling of each film is
measured.[20]

In Vitro drug release test: Here the dissolution medium consisted of phosphate buffer pH
6.8 maintaining a temperature at 37°C ± 0.5°C and with a rotation speed of 50 rpm. The
backing layer of buccal patch is attached to the glass disk with instant adhesive material and
the disk is allocated to the bottom of the dissolution vessel. Five (5) ml sample can be
withdrawn at predetermined time intervals and analyzed for drug content at suitable nm using
a UV spectrophotometer.[20]

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Ex-Vivo mucodhesion strength test: Fresh buccal mucosa (sheep and rabbit) is collected
and used within 2 hours of slaughter and separated by removing underlying fat tissues. The
buccal mucosa cut into pieces and a piece is tied in the open mouth of a glass vial, filled with
phosphate buffer (pH 6.8). This glass vial is tightly fitted into a glass beaker filled with
phosphate buffer (pH 6.8, 37°C ± 1°C) so it just touched the mucosal surface. The patch is
stuck to the lower side of a rubber stopper with cyano acrylate adhesive. Before the study two
sides of the balance made equal and balanced with a 5g weight. The 5g weight is removed
from the left hand side pan which loaded the pan attached with the patch over the mucosa.
The balance is kept in this position for 5 minutes of contact time. The water is added slowly
at 10 drops/min to the right-hand side pan until the patch detached from the mucosal
surface.[2]

Permeation study: The receptor compartment is filled with phosphate buffer pH 6.8 and is
maintained by stirring with a magnetic bead at 50 rpm. Samples are withdrawn at
predetermined time intervals and then analyzed for drug content.[20]

Ex-vivo mucoadhesion time: The fresh buccal mucosa is tied on the glass slide and a
mucoadhesive patch is wetted with 1 drop of phosphate buffer pH 6.8 and pasted to the
buccal mucosa by applying a light force with a fingertip for 30 seconds. The glass slide is
then put in the beaker filled with 200 ml of the phosphate buffer of pH 6.8 kept at 37°C ±
1°C. After 2 minutes, a 50-rpm stirring rate is applied to simulate the buccal cavity
environment and after that patch adhesion is monitored for 12 hours. The time for changes in
color, shape, collapsing of the patch and drug content is noted.[2]

8. Measurement of mechanical properties: Mechanical properties of the patches can be

evaluated using a microprocessor based advanced force gauze equipped with a motorized
test. Using a tensile tester mechanical properties of the films (patches) include tensile
strength and elongation at break is evaluated. Film strip that has dimensions of 60 x 10
mm and without any visual defects cut and positioned between two clamps separated by a
distance of 3 cm. Clamps designed to secure the patch without crushing it during the test,
the lower clamp held stationary and the strips are pulled apart by the upper clamp moving
at a rate of 2 mm/sec until the strip breaks. Force and elongation of the film at the point
when the strip breaks is recorded. The tensile strength and elongation at break values are
calculated using the formula.
[T= (M X g) / (B X T) ]

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Where, M - is the mass in gm, g - is the acceleration due to gravity 980 cm/sec2, B - is the
breadth of the specimen in cm, T - is the thickness of specimen in cm. Tensile strength
(kg/mm2) is the force at break (kg) per initial cross sectional area of the specimen (mm2).

9. Stability study in human saliva: The stability study of optimized bilayered and
multilayered patches is performed in human saliva. The human saliva is collected from
humans with age between 18-50 years. In separate petridishes containing 5ml of human
saliva buccal patches are placed in a temperature controlled oven at 37°C ± 0.2°C for 6
hours. Films stability study is carried out for all the batches according to ICH guidelines.

Permeability Measurement using animal models: To perform this study the most
commonly used animal models are dogs, rabbits, and pigs. A general criterion is the
resemblance of the animal mucosa to the oral mucosa of human beings in both ultra-structure
and enzyme activity for selecting an in vivo animal model that represent the physical and
metabolic barriers of the oral mucosa.[20]

CONCLUSION
Buccal drug delivery offers numerable advantages in terms of administration, accessibility
and withdrawal, retentivity, high patient compliance, economy and low enzymatic activity.
This system has applications from different angles includes avoiding first-pass metabolism in
the liver and pre-systemic elimination in the gastrointestinal tract. Also this area is well suited
for a retentive device and appears to be acceptable to the patient. Another advantage is to
accommodate drug permeation the permeability in the local environment of the mucosa can
be controlled and manipulated with the right dosage form design and formulation. Buccal
drug delivery is a promising area for continued research with the aim of systemic delivery of
orally inefficient drugs as well as a feasible and attractive alternative for noninvasive delivery
of potent peptide and protein drug molecules. However, in the area of buccal drug delivery
for safe and effective buccal permeation the absorption enhancers are crucial component for a
prospective future. Mucoadhesive systems may play an increasing role in the development of
new pharmaceuticals with the great influx of new molecules stemming from drug research.
Due to success, advantages and ease of access of drug delivery through oral mucosal tissue
the buccal and sublingual routes have favourable opportunities and many formulation
approaches although the current commercially available formulation are mostly limited to
tablets and films. So it can be said that the buccal mucosa offers several advantages for
controlled drug delivery for long period of time and also favourable area for systemic

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delivery of orally unsatisfactory drugs and attractive alternative for non-offensive delivery of
potent peptide and protein drug molecule. For improving drug absorption especially for the
new generation oral mucoadhesive dosage forms will be an exciting research in coming days.

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