MUCOADHESIVE
DRUG DELIVERY
SYSTEM
Done by :
Fatima Khalid
Third stage
Introduction
Since the early 1980s, the concept of mucoadhesion has
gained
considerable
interest
in
pharmaceutical
technology. Adhesion can be defined as the bond
produced by contact between a pressure sensitive
adhesive and a surface. The American Society of Testing
and Materials has defined it as the state in which two
surfaces are held together by interfacial forces, which may
consist of valence forces, interlocking action or both.
Mucoadhesive drug delivery systems prolong the residence
time of the dosage form at the site of application or
absorption. They facilitate an intimate contact of the
dosage form with the underlying absorption surface and
thus improve the therapeutic performance of the drug. In
recent years, many such mucoadhesive drug delivery
systems have been developed for oral, buccal, nasal,
rectal and vaginal routes for both systemic and local
effects.
Defination
Mucoadhesive drug delivery system may be defined as a
drug delivery system which utilize property of bioadhesion
of certain water soluble polymers which become adhesive
on hydration and hence can be used for targeting a drug
to a particular region of the body for extended periods of
time.
Principle
During the 1980s mucoadhesion began to be applied to
drug delivery systems .It consists of the incorporation of
adhesive molecules into some kind of pharmaceutical
formulation intended to stay in close contact with the
absorption tissue releasing the drug near to the action site
theraby increasing its bioavailability and promoting local or
systemic effects .
The potential use for mucoadhesive systems as drug
carriers lies in its prolongation of the residence time at the
absorption site allowing intensified contact with the
epithelial barrier .On other hand adhesion of preparation
onto mucous membrane can be impaired by the
mucociliary clearance system and by using bioadhesive
molecules to retain the preparation at the action site and
to direct the drug to a specific site or tissue . Mucousl
membranes of human organism are relatively permeable
and allow fast drug absorption .They are characterized by
epithelial layer whose surface is covered by mucus . The
mucus contains glycoproteins ,lipids ,inorganic salts and
95%water .
There are number of materials used for developing such
systems .The most studies material are the polymers derived
from polyacrylic acid such as polycarbophil and carbomers
,
polymers
derived
from
cellulose
such
as
hydroxyethylcellulose. chitosan and derivatives and mor
recently,lectins and their derivatives.
The mucoadhesive drug delivery system is cumulative for
delivering the drugs which have narrow absorption window
at the target site to optimize their usefulness.
The oral route is the most ancient as well as preferred by the
patient being convenient to take similarly in mucoadhesive
dosage forms has inclined patients towards due to ease of
drug administration and painless administration .There are
also nasal ,vaginal,ocular and rectal drug delivery systems .
Mucoadhesive drug delivery systems can be delivered by
various routes:•
•
•
•
•
•
Buccal delivery system
Oral delivery system
Vaginal delivery system
Rectal delivery system
Nasal delivery system
Ocular delivery system
Bioadhesion and Mucoadhesion
The term bioadhesion can be defined as the state in
which two materials, at least one biological in nature, are
held together for an extended period of time by interfacial
forces. In biological systems, bioadhesion can be classified
into 3 types:
Type 1: adhesion between two biological phases, for
example, platelet aggregation and wound healing.
Type 2: adhesion of a biological phase to an artificial
substrate, for example, cell adhesion to culture dishes and
biofilm formation on prosthetic devices and inserts.
Type 3: adhesion of an artificial material to a biological
substrate, for example, adhesion of synthetic hydrogels to
soft tissues and adhesion of sealants to dental enamel.
For drug delivery purposes, the term bioadhesion implies
attachment of a drug carrier system to a specified
biological location. The biological surface can be epithelial
tissue or the mucus coat on the surface of a tissue. If
adhesive attachment is to a mucus coat, the phenomenon
is referred to as mucoadhesion.
Leung and Robinson described mucoadhesion as the
interaction between a mucin surface and a synthetic or
natural polymer. Mucoadhesion should not be confused
with bioadhesion; in bioadhesion, the polymer is attached
to the biological membrane and if the substrate is mucus
membrane the term mucoadhesion is used.
Mucoadhesive polymer are classified
as follows:
 Classification Mucoadhesive polymer are classified as
follows: First generation polymer:
 Anionic polymer: poly(-acrylic acid), carbopol,
polycarbophil, Cationic polymer: Chitosan
 Second generation polymer: Lecithins, bacterial
adhesion
 New generation polymer: Thiomers
Characteristics of an ideal
mucoadhesive polymers:
 The polymer and its degradation products should be
nontoxic and should be nonabsorbable from the
gastrointestinal tract.
 It should be non-irritant to the mucous membrane.
 It should preferably form a strong non-covalent bond
with the mucin-epithelial cell surfaces.
 It should adhere quickly to most tissue and should
possess some site-specificity.
 It should allow incorporation to the daily dose of the
drug and offer no hindrance to its release.
 The polymer must not decompose on storage or during
the shelf life of the dosage form.
 The cost of polymer should not be high so that the
prepared dosage form remains competitive.
Mechanism of action:
The mechanism of mucoadhesion is generally divided into
two steps:
1. the contact stage : is characterized by the contact
between the mucoadhesive and the mucus
membrane, with spreading and swelling of the
formulation, initiating its deep contact with the mucus
layer. Materials are activated by the presence of
moisture. Moisture plasticizes the system, allowing the
mucoadhesive molecules to break free and to link up
by weak van der Waals and hydrogen bonds.
2. the consolidation stage : Essentially, there are two
theories explaining the consolidation step: the
diffusion theory and the dehydration theory.
According to the diffusion theory, the mucoadhesive
molecules and the glycoproteins of the mucus
mutually interact by means of interpenetration of
their chains and the building of secondary bonds. For
this to take place, the mucoadhesive device has
features favoring both chemical and mechanical
interactions. For example, molecules with hydrogen
bond building groups (–OH, –COOH), an anionic
surface charge, high molecular weight, flexible
chains and surface-active properties, which help in
spreading throughout the mucus layer, can present
mucoadhesiveproperties.
.
Mucoadhesion theories
Mucoadhesion is a complex process and numerous
theories have been proposed to explain the mechanisms
involved.
These theories include :
1. The wetting theory: It explains the contact angle of
liquids on the substrate surface is lower, then there is a
greater affinity for the liquid to the substrate surface.
2. The diffusion theory: Due to the presences of polymeric
chains on the substrate surfaces, across the adhesive
interface thereby forming a networked structure.
3. The mechanical theory: It explains the diffusion of the
liquid adhesives into the micro-cracks and irregularities
present on the substrate surface thereby forming an
interlocked structure which gives rise to adhesion.
4. The electronic theory: Due to the transfer of electrons
amongst the surfaces resulting in the formation of an
electrical double layer, giving rise to attractive forces.
5. The adsorption theory: Due to the presence of
intermolecular forces (hydrogen bonding) and Vander
Waal forces, results in adhesive interaction amongst the
substrate surfaces.
6. The cohesive theory: The phenomena of bioadhesion
are mainly due to the intermolecular interactions
amongst like-molecules.
Advantages
1. MDDS offer several advantages over other controlled
oral controlled release systems by virtue of prolongation
of residence of drug in GIT.
2. Targeting & localization of the dosage form at a
specific site.
3. High drug flux at the absorbing tissue.
4. MDDS will serve both the purposes of sustain release &
presense of dosage form at the site of absorption.
5. Excellent accessibility.
6. Painless administration.
7. Low enzymatic activity & avoid of first pass metabolism.
Disadvantage
1. drus which irritate the oral mucosa have a bitter or
unpleasant taste ,odour,can be administered by this
rout.
2. drugs,which are unstable at buccal pH can not be
administered by this rout.
3. only drug with small does requirments can be
administered.
4. drug may swllow with saliva and loses the
advantagesof buccal rout.
5. only those drugs,which are absorbed by passive
diffusion can be administered by this rout.
6. eating and drinking may become restricted.
*TABLE: Commercial Mucoadhesive
Drug Delivery System
FUTURE POTENTIAL AND RESEARCH
DIRECTION
Research in buccal drug delivery has revealed
remarkable growth and advances in the past few
decades. The buccal mucosa holds a great promise for
systemic delivery of orally inefficient drugs as well as a
feasible and attractive alternative for non-invasive
delivery of potent peptide and protein drug molecules.
Mucoadhesive drug delivery systems offer unique
carrier system for many pharmaceuticals and can be
modified to adhere to any mucosal tissue, including
those found in oral cavity, gastrointestinal tract, vagina,
eye etc. One of the areas of interest is the novel buccal
adhesive delivery system, where the drug delivery is
directed towards buccal mucosa by protecting the
local environment.
In spite of significant advances in the field of
mucoadhesion, there is no consensus between
scientists in relation to the mechanisms of the
interaction between materials and components of
mucosal tissue. Many scientists have addressed the
development of MBDDS and studied the efficacy of
their use, though here too there remain significant
gaps, as there is no generally accepted method for
assessing mucoadhesive properties.
The lack of standardized techniques often leads to
discordant and unclear results. Efforts have to be made
to develop standardized in vitro and ex vivo biological
models that allow one to characterize and compare
different materials and formulations in terms of their
capability to promote drug absorption via the buccal
route.
Looking into the future, researchers find the fate of
buccal adhesive drug delivery turning towards vaccine
formulations and delivery of small proteins/peptides.
Microparticulate bioadhesive systems are particularly
interesting because they offer protection to
therapeutic entities as well as the enhanced absorption
that result from increased contact time provided by the
bioadhesive component. Mucoadhesion can clearly
play a fundamental role as non-parenteral drug
delivery systems for protein formulations, as well as
vaccines able to attach to mucous membranes to
stimulate local immunity.
At the current global scenario, scientists are finding
ways to develop buccal adhesive systems through
various approaches to improve the bioavailability of
orally less/inefficient drugs by manipulating the
formulation strategies. Polymeric science needs to be
explored to find newer mucoadhesive polymers with
the added attributes of being biodegradable,
biocompatible, non-toxic, mucoadhesive for specific
cells or mucosa.
THANK YOU……..