938-Article Text-2359-1-10-20210415
938-Article Text-2359-1-10-20210415
938-Article Text-2359-1-10-20210415
ABSTRACT
Pharmaceutical scientists around the globe have been seeking to discover as an alternative to injections over the last few,
transdermal and transmucosal routes decades. The buccal cavity mucosa the most convenient and easily available site for the
distribution of local and systemic therapeutic agents was found to be dosage forms among the numerous transmucosal
sitesavailable.Theories and various polymers used in mucoadhesive drug delivery. Mucoadhesive polymers increases the
residence time, prolong the absorption, enhances solubilityand dissolution characteristics of poorly soluble drugs. In addition,
we are focused on the latest generation of mucoadhesion polymers, led by the latest formulation of mucoadhesive for the
distribution of oral drugs, such as thiolated polymers. A good insight into mucoadhesion polymers, the mucoadhesive
phenomenon and the factors that can affect polymer mucoadhesion is given in the current analysis. The systematic drug
delivery has been investigated for buccal mucosa and local drug treatment or therapy is subjected to first pass metabolism. Oral
mucosa drug delivery by discussing the structural features of mucosa, mechanism of mucoadhesion. General consideration in
design of mucoadhesive buccal dosage forms, permeation enhancers and the various evalution method along with literature
survey of the buccal mucoadhesive.
Keywords: Mucoadhesive polymer, oral mucosa, enhances solubility, drug delivery, permeation enhancer.
A R T I C L E I N F O: Received 14 Jan 2021 ; Review Complete 21 Feb 2021; Accepted 25 March 2021; Available online 15 April. 2021
Cite this article as:
Sharma M, F.R. S, Yadav RP, Patel AK, Kumar Y, Mucoadhesive polymers for buccal drug delivery system: An overview, Asian
Journal of Pharmaceutical Research and Development. 2021; 9(2):57-64. DOI: http://dx.doi.org/10.22270/ajprd.v9i2.938
INTRODUCTION
They are non-suitable for high dose of drug. Free protein: 0.5-1%
It should be non-uniform toxic and non-absorbablefrom Mucus glycoproteins are high molecular proteins
the site of absorption such as buccal, vaginal etc. possessing attached oligopolysaccharide units. They are the
It should be non-irritant to the membrane of mucus.
a. L-fructose medication
It should have an optimum degree of cross linking
b. Galactose-D
density, pH and hydration.
c. Sialic acid
It should bind to moist tissue easily and have some site
specificity.
In the handling of the dosage form or during its shelf Functions of mucus-
life, it is not necessary for the polymer to decompose. • Cell-cell adhesion
Overview of oral mucosa [4, 5] • Lubrication
The total surface area of oral cavity 100cm2 and is lined
with mucous membranes. The several distinict maturation Mucoadhesive Dosage Forms [2, 6]
trends, referring to the tissue's functional demands. The mucoadhesive dosage forms are providing intimate
Kertatinized epithelium (dehydrated, chemically resistant to contact with the dosage form in order to extend the drug
mechanical toughness) is found to less flexible forms the action, the absorbing surface and to increase the dosage
matisfactory the gingiva mucosa and part of the rough part residence time type at the absorbing surface. There are
of the guma Plate Sheet. The surface of the pavement various mucoadhesive dosage form are given below.
distensible lining of the mucosa of the soft palate, mouth
floor, lips and cheek is formed by non-keratinized 1. Gastrointestinal drug delivery.
epithelium (flexible).There are three layer layers of the 2. Nasal delivery system
epithelium of the mucosa is basement membrane and 3. Ocular delivery system.
connective tissue.The membrane of the basement forms a 4. Buccal and sublingual delivery system.
distinctive layer between the connective tissue and the 5. Vaginal and rectal delivery System.
epithelium. These tissues, which are also reffered to as the
lamina propria, consist of collagen fibers, a connective Gastrointestinal drug delivery:
supporting layer tissue, vessels in the blood and smooth
muscles. It is also a viscous elastic hydrogel, and primarily The concept of mucoadhesives started with the simple need
consists of 1– 5% of the above mentioned, Water insoluble to locate a drug at some GI locations tract. Therefore, by
glycoproteins, 95-99 percent water, and small amounts of obtaining a substantial increase in the residence time of the
some other elements, such as proteins, enzymes drug for local drug effect and allowing once-daily dosing,
electrolytes, nucleic acids and Based on the origin of the the primary objective of using mucoadhesive systems orally
mucosal secretion in the body, This composition can differ. would be achieved. The turnover of mucus, that is, the
continuous development of mucous by the gastric mucosa
to replace the missing mucous by contractions and also
dilution of the stomach material limits the possibilities of
mucoadhesion as a gastro retentive force.
Nasal drug delivery system:
It is one of the most important features of the nasal route is
avoids first-pass hepatic metabolism, thereby reducing
metabolism. Addition of mucoadhesive excipient such as
chitosan results in a decreased clearance rate. The nasal
mucosa has a surface area of about 150-200 cm2 and the
residence time in the nasal mucosa is between 10 to 30 min.
Dehydration theory:
Materials that can quickly gelify in an aqueous atmosphere
when put in contact with the mucus can cause dehydration
due to the difference in osmotic pressure, according to the
dehydration principle. This method contributes to the
formula and mucus mixture and will thereby increase the
time of contact with the mucous membrane. For solid
formulas or extremely hydrated forms, the dehydration
principle does not apply.
Contact stage:
Themucoadhesive drug delivery systems and the interaction
between the mucoadhesive and the mucous membrane, with
the spreading and swelling of the mucoadhesive membrane,
characterize the point formulation initiatingthe profound
interaction with mucus layer.In these cases, peristalsis, the
motion of organic movement, may explain mucoadhesion
fluids in the organ cavity, or by Brownian motion. If the
particle reaches the mucous surface, repulsive forces
(osmotic friction, electrostatic repulsion, etc.) and attractive
forces will come into contact with it (van der Waals forces
and electrostatic attraction). Figure: 4 The mucoadhesion hypothesis of dehydration.
Mechanical theory
This hypothesis assumes adhesion to be due to the filling by
a mucoadhesive solvent of the irregularities on a rough
surface. Such roughness increases the interfacial region
available for contacts, thereby helping to dissipate energy
and can be considered the most relevant process
phenomena. Intrinsic the polymer's variables are related to
its molecular weight, concentration and stability in the
chain. Mucoadhesion increases with molecular weight for
linear polymers, but for nonlinear polymers the same
relationship does not hold. In the mucus layer, the thickness
will range from 50 to 450 μm stomach. Less than 1µm
located in the oral cavity and mucoadhesion which occurs
in an array of different situations.
Figure5: Schematic diagram of the touch angle impactdevice and mucus Muco-adhesive polymers: 8
membrane on Bioadhesion.
Muco-adhesive polymers are mainly water soluble in
The spreadability coefficient, SAB, can be calculated from nature. These polymers have swellable networks. These
the difference between the surface energies γB and γA and cross-link agents have various important properties, such as
the interfacial energy γAB, as indicated in equation are fast wetting, better mutual adsorption, and better ability to
given below: penetrate and interpenetrate within the polymer and oral
SAB = YB –YA-YAB mucus, which are essential for muco-adhesion.These muco-
………………….1
adhesive polymers which have ability to bind with the
The greater the individual surface energy of mucus and mucus present on the epithelial cells surfaces can be
device in relation to the interfacial energy, the greater the divided in three classes
adhesion work, WA, that the greater the energy needed to
separate the two phases. When polymers are put in water, they have the potential to
become sticky. In order to attain greater stickiness, these
WA = YA + YB –YAB ……………………..2 polymers also have their own muco-adhesion
Diffusion theory strength.Examples are collagen, gelatin, starch, alginate,
and agarose Polymers which, because of their electrostatic
Diffusion theory explains the interpenetration to an nature, are capable of adhering to the epithelial surface
appropriate extent of both polymer and mucin chains to (Hydrogen bonding can play significant role in these
ISSN: 2320-4850 [60] CODEN (USA): AJPRHS
Sharma et al Asian Journal of Pharmaceutical Research and Development. 2021; 9(2): 57-64
found to be reduced by putting the electrode into contact of a pH buffer of phosphate 6.8. The research was
with the surface of the patch and allowing it to balance for conducted at 37° C ± 0.5 ° C, with a rotating speed of 50
1 minute. rpm. Buccal tablet backing layer membrane attached to the
glass disk with instant adhesive adhesive (cyanoacrylate
Swelling studies
adhesive). 5 ml of sample is removed as a fixed interval of
Swelling lifts the patch's weight: time and supplemented with fresh medium. The samples
were screened into Whatman filter paper and analyzed by
On a pre-weighed cover slip, a drug-loaded patch of 1x1
UV spectrophotometry at a suitable nm after sufficient
cm2 was retained and weighed, and then 50 ml of
dilution.
phosphate buffer (pH 6.6) was applied. After five minutes,
the cover slip was cut and measured for up to 30 minutes. In vitro drug permeation:
Owing to water absorption and swelling of the patch, the
The in vitro oral drug permeation study of drugs via the
weight difference results in a weight rise.
oral mucosa of sheep or goat is performed at 37 ° C ± 0.2 °
Ex vivo mucoadhesive strength: C using Keshary-Chien or Franz type glass diffusion cell. It
contains the fresh buccal mucosa donor and receptor
Determing the ex vivo mucoadhesive strength a modified
compartments that have been connected. The core side of
balance method is used. The fresh mucosa buccal of goat
the mucosa and the compartments were facing the oral
or sheep obtained and used within 2 hours of slaughter. The
tablet clamped together. One ml buffer with phosphate (pH
mucosal membrane was cleaned at 37 °C with distilled 6.8). It is positioned in the donor compartment and the
water and then with a phosphate buffer (pH 6.8). The oral receptor compartment is located in the phosphate buffer
mucosa was cut into small pieces and washed again with a
(pH 7.4).One ml sample can be removed at a predetermined
phosphate buffer (pH 6.8). A piece of buccal mucosa was
time interval and tested for drug content at suitable nm
attached to the glass vial, which was packed with a
using a UV spectrophotometer.
phosphate buffer. Prior to the study, the two sides of the
modified balance were made equal by putting a 5 g weight Study of Stability in Human Saliva:
on the right side of the pan. A weight of 5 g was removed
According to the ICH guidelines stability study of fast
from the right side of the pan, lowering the pan over the
dissolving films is carried out for all the batches. After the
mucosa along with the tablet. The balance was kept in this
predetermined interval of time, the films were evaluated for
position for a contact time of 5 minutes. Equivalent to
the disintegration time, drug content and physical
weight, with an infusion set of 100 drops per minute on the
appearance. Optimized mucoadhesive patch formulation
right side of the pan, the water was added at a slow rate
stability studies were performed at percent 40° C, 37 ± 5°
until the tablet separated from the mucosal surface. Buccal
C& 75 ± 5 % RH up to three months◦. After three months,
tablet's power of mucoadhesive in grams. At 37 °C ± 1 °C,
the worth of all of the parameters remains the same as their
the glass vial was closely fitted into a glass beaker filled
values and there are small improvements in the value of the
with a phosphate buffer (pH 6.8) so it barely reached the
efficiency of volume trapping, percent elongation & percent
surface of the mucosa.
drug release after eight hours.
Ex- vivo mucoadhesive time:
CONCLUSION
Determining ex vivo mucoadhesion time conducted on
Mucoadhesive has innumerable advantages in terms of
newly cut buccal mucosa after application of the buccal
accessibility, administration and low enzymatic activity and
patch of goat or sheep. The fresh buccal mucosa was tied
high enforcement with patients. Researchers are also
on the glass slide and 1 drop of phosphate buffer was
looking at novel drug delivery mechanisms beyond
moistened on the mucoadhesive core side of each tablet.
conventional polymer networks to discover some. In order
(pH 6.8) and stuck to the buccal mucosa of the sheep by
to understand the different processes of mucoadhesion and
applying light force at the tip of the finger for 30 seconds.
increased permeation of active agents and dosage types,
The glass slide was then mounted in a beaker which was
mucoadhesive drug delivery systems are being introduced
filled with 200 ml of pH 6.8 phosphate buffer and held at
to provide sustained interaction at the site of administration.
37 °C ± 1 °C.After two minutes, a stirring rate of 50 rpm
The formulation of method of mucoadhesive drug delivery
was applied to mimic the condition of the oral cavity, and
depend on the selection of suitable polymer with excellent
tablet adhesion was tracked for 12 hours. The time taken to
mucoadhesive properties and biocompatibility.
remove the tablet from the buccal mucosa was noted as the
Mucoadhesive polymers have seen dramatic progress in
time for mucoadhesion.
both individual treatments and more general patient
In vitro drug release: compliance to maximize contact time with a wide range of
medications and routes of administration. Mucoadhesive
Pharmacopoeia (USP) XXIII in the United States rotating drug delivery has diverse applications including
paddle method used for studying the release of drugs rate development of novel mucoadhesive, design of the novel
from the bilayered tablets. The dissolution medium consists
devices, mechanism and permeation enhancement.
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