Mucosal Drug Delivery

System
Prepared By : Dr. Tejas J. Patel
Associate Professor
Department of Pharmaceutics
SNLPCP, Umrakh
 Introduction
⦿ The concept of mucoadhesion was introduced
in the field of controlled release drug delivery
systems in the early 1980s.
⦿ Mucoadhesion is commonly defined as the
adhesion between two materials, at least one
of which is a mucosal surface.
⦿ For drug delivery purpose, the term
bioadhesion implies attachment of a drug
carrier system to a specific biological location.
⦿ The biological surface can be epithelial tissue.
If adhesive attachment is to a mucus coat, the
phenomenon is referred to as mucoadhesion.
⦿ Mucoadhesion is the relatively new and
emerging concept in drug delivery.
⦿ Mucoadhesive dosage forms may be
designed to enable prolonged retention
at the site of application, providing a
controlled rate of drug release for
improved therapeutic outcome.
⦿ The mucosal routes for drug delivery are:
• Buccal route
• Nasal route
• Ocular route
• Rectal route
• Vaginal route
• Gastrointestinal route.
 Advantages
⦿ Provides a relatively rapid onset of action as
compare to the other non-oral routes, hence,
has a high patient acceptability.
⦿ Improved patient compliance due to the easy
application of dosage forms in comparison to
the injections and don’t provide any painful
sensation
⦿ Mucosal membranes are highly vascularised
so that the administration as well as removal of
a dosage form is easy.
⦿ The sustained drug delivery can be achieved
by using the mucoadhesive polymers of ‘SR’
grades.
⦿ Avoid first pass metabolism effect.
⦿ Due to the high extent of perfusion the
rate of drug absorption is faster.
⦿ Can be easily used in case of
unconscious & less Co-operative patients.

⦿ Drugs, which show poor bioavailability

via oral route, their bioavailability can be
enhanced by formulating their
mucoadhesive delivery systems.
⦿ Side effect that can arise due to oral
administration, such as, nausea and
 Disadvantages
⦿ MDDS are adhere too tightly, too much
force required to remove the formulation
after use, otherwise mucosa could be
injured.
⦿ Costly drug delivery system.
⦿ Some patient suffer unpleasant feeling.
⦿ Unfortunately, the lack of standardized
techniques often leads to unclear results.
⦿ Medication administered orally do not enter
the blood stream immediately.
 Stages of mucoadhesion
⦿ Contact stage: During this stage, when the
mucoadhesive material comes in contact
with mucus membrane, an intimate wetting
occurs between the mucoadhesive and
mucous membrane. Нis wetting of the
mucoadhesive is done by the mucus
present in the mucosal membrane.
⦿ Consolidation stage: By means of different
physicochemical forces of attraction the
mucoadhesive material gets joined to the
mucus membrane and resulting in a long
lasting mucoadhesion. This is called as the
consolidation stage. After these two stages
the process of mucoadhesion completes.
Transmucosal permeability
⦿ Drugs may cross a cell membrane by:
• Passive Diffusion
• Facilitated diffusion
• Active transport
• Pinocytosis
❑ Factor to be considered in the Transmucosal
permeability.
• Lipophilicity of drug
• Salivary secretion
• pH of saliva
• Binding to oral mucosa
• Oral epithelium thickness.
 Mucoadhesive polymer
Mucoadhesive polymer are classified as
follows:
⦿ Natural or semi natural : Agarose, Chitosan,
Gelatin, Starch and Various Gum.
⦿ Synthetic Cellulose derivatives: CMC, HEC,
HPC, HPMC, Methyl Cellulose, MHEC
⦿ Synthetic Poly(acrylic acid) based:
Carbopol, Polycarbophil, Polyacrylate, PEG
and copolymer of acrylic acid.
⦿ Others: PVP, PVA, Polyoxymethylene,
Poloxamers
 Properties Mucoadhesive polymer
⦿ It must be loaded substantially by the active compound.
⦿ Swell in aqueous biological environment of delivery–absorption site.

⦿ Interact with mucus or its components for adequate adhesion.

⦿ When swelled they allow, controlled release of active agent.
⦿ Be excreted unaltered or biologically degraded to inactive, non-
toxic oligomers.
⦿ Sufficient quantities of hydrogen bonding chemical groups.
⦿ Possess high molecular weight.
⦿ Possess high chain flexibility.
⦿ Surface tension that will induce spreading into mucous layer.
 Functional Agent of MDDS
❖ MDDS contain the following functional agents-
1. Mucoadhesive agents : Polyacrylic acid (PAA),
PVA , (NaCMC), Sodium alginate, HPMC, HEC, HPC.

2. Penetration enhancers: Benzalkonium chloride,

Dextran sulfate, Fatty acid, Propylene glycol, Menthol,
Phosphatidylcholine, Polysorbate 80, Sodium EDTA.

3.Enzyme inhibitors: Drug +enzyme inhibitors- improving

the buccal absorption of drugs, particularly peptides.
Like Aprotinin, Bestatin, Puromycin.
e.g. Chemical modification of chitosan with EDTA
produces polymer conjugate chitosan –EDTA that is a
very potent inhibitor of metallopeptidases
(carboxypeptidase)
 Theory of Mucoadhesion
⦿ On the basis of nature and strength of Chemical and
Mechanical bonds, there are following five theories of
mucoadhesion that are been postulated.
1) Electronic theory:
• According to the electronic theory, there is
difference in the electronic structure of mucin
surfaces and bio adhesive system which results in
attaining a electronic gradient.
• Due to presence of this electronic structure
difference the transfer of electrons occurs in these
two systems (mucin surface and bio adhesive system)
when they come in contact with each.
• As a result of this electron transfer there is the
formation of an electronic bi-layer at the interface of
the two surfaces.
• This interfacial bi-layer exerts an attractive force in
the interface of two surfaces that may produce an
effective mucoadhesion
2) Adsorption theory:
• This theory describes the involvement of both
type of chemical bond, that is, primary and
secondary bond in the bio adhesion
mechanism.
• Both the surface that is mucin and drug
delivery system has their own surface energy.
When they come in contact, the adhesion
occurs due to the surface energy and results
in the formation of two types of chemical
bond.
• Primary chemical bond such as covalent
bond, which is strong in nature, thus produces
a permanent bonding, whereas secondary
chemical bond involves Vander-Waals forces,
hydrophobic interaction and hydrogen
bonding, which are weak in nature, thus
produces a semi-permanent bond.
3) Wetting theory :
• This theory is based on the mechanism of
spreadability of drug dosage form across
the biological layer.
• This theory is mainly applicable to liquids or
low viscous mucoadhesive system.
• According to this theory, the active
components penetrate in to the surface
irregularities and gets harden it that finally
results in mucoadhesion.

4) Fracture theory: The fracture theory is

mainly based on the fact that, the force
required to detach the polymeric chain
from the mucin layer is the strength of their
adhesive forces, this strength may be also
called as fracture strength.
5) Diffusion interlocking theory :
• This theory describes the involvement of a
mechanical bond between the polymeric chain
of drug delivery system and polymeric chain of
mucus membrane, that is, glycol proteins.
• When two surfaces are in intimate contact, the
polymeric chain of drug delivery system
penetrates in to the glycoprotein network.
• According to this theory, the bioadhesion
basically depends on the diffusion coefficient of
both polymeric chains.
• Some factors that may influence the inter
movement of polymeric chain are molecular
weight, cross linking density, chain flexibility and
temperature in order to achieve a good bio
adhesion, the bio adhesive medium should have
a similar solubility with glycoprotein resulting in
effective mucoadhesion.
 Formulation consideration of
Buccal delivery systems
⦿ The buccal mucosa lines the inner cheek, and buccal
formulations are placed in the mouth between the
upper gingivae (gums) and cheek to treat local and
systemic conditions.
⦿ The buccal route provides one of the potential routes
for typically large, hydrophilic and unstable proteins,
oligonucleotides and polysaccharides, as well as
conventional small drug molecules.
⦿ The oral cavity has been used as a site for local and
systemic drug delivery.
⦿ The general considerations in buccal dosage form
design includes :
1) Pharmaceutical considerations.
2) Physiological considerations.
3) Pathological considerations.
4) Pharmacological considerations.
1) Pharmaceutical considerations:
• The release of core from the dosage form can be
retarded by its solubility in saliva.
• The absorption of weakly water soluble drugs can
be increased by solubilizing the drug in Cyclodextrin
and administered via buccal route.
• The physicochemical characteristics, morphological
characters of the drug all influence the desirable
drug release and absorption.
• In case of dosage forms, for enhancing the
effectiveness and acceptability, some excipients
are incorporated.
• Various permeation enhancers increase
permeability of buccal mucosa.
• Enzyme inhibitors may be included in the dosage
forms to prevent enzyme degradation and pH
modifiers may be included in order to temporarily
modulate the microenvironment at the application
site for better drug absorption.
2) Physiological considerations:
• Challenges of drug delivery to the oral
cavity are Constant flow of saliva and
mobility of tissues.
• The residence time of drugs in the oral
cavity is typically short, in the range of
greater than 5-10 min.
• The problem is mainly overcome by use of
buccal formulation.
• The device size is 1- 3 cm and daily dose of
25 mg in case of buccal delivery and
ellipsoid shape favors to be more
acceptable and thickness is usually limited
to few mm for buccal formulation.
3) Pathological considerations:
• Thickness of epithelium is affected
mainly with many diseases in which the
barrier of mucosa results in alteration.
• Mucus properties are influenced with
some diseases, hence in pathologic
conditions which complicate bio
adhesive device to be retention and at
site of application.
4) Pharmacological considerations:
• In case of systemic circulation and local therapy
buccal dosage form is designed for oral mucosa.
• The dosage form is affected mainly due to drug
characteristics, target site of action and at the
treated site.
• Drug absorption depends on the partition
coefficient of the drug. Generally lipophilic drug
absorb through the transcellular route, where as
hydrophilic drug absorb through paracellular route.
• Residence time, local concentration of drug in the
mucosa and drug transported across the mucosa
into the blood are the responsible factor for local
and systemic drug delivery.
• Ideal properties of novel buccal drug
delivery systems
Should release the drug in a
controlled fashion
Unidirectional way of drug release
towards the mucosa.
Should facilitate the rate and extent
of drug absorption.
Should not cause any irritation or
inconvenience to the patient.
Should not interfere with the normal
functions such as talking, drinking etc.
 Evaluation of MDDS
⦿ Measuring the force of attachmentt
⦿ In vivo residence time study
⦿ GI transit study using radio-opaque
markers (Barium sulfate)
⦿ Fluorescent probe method (pyrene and
fluorescein Isothiocyanate)
⦿ Thumb test
Thank You