A

seminar
on

Mucoadhesive drug delivery system

By

Miss. Duduskar Anita Ankush

Under the Guidance of

Dr. Pawar P.K.
Head of Department Pharmaceutics
Gourishankar Institute of
Pharmaceutical Education &
Research Limb, Satara.
(2015-2016)
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• Introduction
• Basics ,concepts & mucosal membrane.
• Need of mucoadhesive DDS
• Mechanism of mucoadhesion
• Theories mucoadhesion
• Sites of mucoadhesion
• Penetration enhancer
• Mucoadhesive polymer
• Factor affecting mucoadhesion
• Advantages & Disadvantages
• Mucoadhesive dosage form
• Evaluation
• Case study
• Reference

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• Mucoadhesive drug delivery system interact with the
mucus layer covering the mucosal epithelial surface,
& mucin molecules & increase the residence time of
the dosage form at the site of the absorption.

• Mucoadhesive drug delivery system is a part of

controlled delivery system.

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• Since the early 1980,the concept of Mucoadhesion has
gained considerable interest in pharmaceutical
technology.
• combine mucoadhesive with enzyme inhibitory &
penetration enhancer properties & improve the patient
complaince.
• MDDS have been devloped for buccal ,nasal,rectal
&vaginal routes for both systemic & local effects.
• Hydrophilic high mol. wt. such as peptides that cannot be
administered & poor absorption ,then MDDS is best
choice.

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 - Inner layers called mucosa -Tendency substance to remain
- Inner epithelial Cell lining adhered to surface
Covered with viscoelastic fluid. -If substance adhere to
Biological mucosal layers is
-Secreted by Goblet cells
called as Mucoahesion
-Composed of water and mucin
-Other components include proteins,
lipids and mucopolysaccharides
,electrolytes
-Main role is protective and
lubricates

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 What is mucus ?
• Mucoadhesiveinner layers called mucosa inner epithelial cell
lining is covered with viscoelasticfluid
• Composed of water and mucin.
• Thickness varies from 40 μm to 300 μm
• General composition of mucus
• Water…………………………………..95%
• Glycoproteinsand lipids……………..0.5-5%
• Mineral salts……………………………1%
• Free proteins…………………………..0.5-1%

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General structure of mucous layer

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 Functions of mucus
• Protective : Particularly from its hydrophobicity

• Barrier : In tissue absorption of the drugs and

influence the bioavailability.
• Adhesion : Mucus has strong cohesion properties

• Lubrication :keep mucosal membrane moist.

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Avoidance
Avoidance Better
Betterabsorption
absorption
ofof ofofpeptide
peptideby
by
First penetration enhancer
Firstpass
pass penetration enhancer
Metabolism
Metabolism

WHY ?

Prolong Localization
Localization
Prolong
ofofdrug
drugatat
residence
residencetime given
time givensite
site

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 Mechanisms of mucoadhesion
• The mechanism responsible in the formation of
mucoadhesive bond
• Step 1 : Wetting and swelling of the polymer(contact
stage)
• Step 2 : Interpenetration between the polymer chains
and the mucosal membrane
• Step 3 : Formation of bonds between the entangled
chains (both known as consolidation stage)

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 Step-I
• Wetting and swelling step occurs when polymer
spreads over the surface of mucosal membrane to
develop intimate contact
• Swelling of polymer occur because the components
of polymer have an affinity for water

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 Step-II
• In this step the mucoadhesive polymer chain and the
mucosal polymer chains intermingle and entangles to
form adhesive bonds
• Strength of bonds depends upon the degree of
penetration of the two polymer groups

Interpenetration of mucoadhesive and mucous polymer chains

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 Step-III
• This step involves formation of weak chemical bonds
between the entangled polymer chains
• Bonds includes primary bonds such as covalent bonds
and secondary interactions such as vanderWaalsand
hydrogen bonds

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• Electronic theory
• Wetting theory
• Adsorption theory
• Diffusion theory
• Fracture theory

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1) Electronic theory
-Attractive electrostatic forces between glycoprotein
mucin network & the bioadhesive material.

2) Wetting theory
-Ability of bioadhesive polymers to spread & develop
intimate contact with the mucous membrane.
3) Adsorption theory
-Surface forces ( covalent bond, ionic bond, hydrogen
bond & van der waals forces) resulting in chemical
bonding

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4) Diffusion theory
-Physical entanglement of mucin strands and flexible
polymer chains.

5) Fracture theory
-Analyses the maximum tensile stress develop during
detachment of the BDDS from mucosal surfaces

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Different routes of targeting
MDDS

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 Penetration enhancer
• Substances that facilitate the permeation through mucosa are
referred as permeation enhancers .
• Safe and non toxic, non irritating and non allergenic

• Pharmacologically and chemically inert

• They should have no pharmacological activity within the body

• Eg. Benzalkonium chloride , Dextran sulfate ,Fatty acid ,

Propyleneglycol, Men ,Sodium EDTA etc.

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 Mucoadhesuve polymers
• They are water soluble and water insoluble polymers which
are swellable networks joined by cross linking agent
• Characteristic of ideal polymer
• Degradation products should be non toxic and non absorbable
from GIT
• Good spreadibility, wetting, swelling and biodegradable
properties
• Optimum molecular weight
• Non irritant to mucous membrane
• Form a strong non-covalent bond with mucin epithelial cell
surface

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Natural and semisynthetic Synthetic

Agarose Carbopol

Chitosan PVA

Gelatin PVP

Pectin Thiolated polymer

CMC Methacrylic acid

Thiolated CMC Polycarbophil

HPMC

Hydroxypropylcellulose
Soluble Insoluble

CMC, Sodium CMC, HPMC, MC, PVA, Carbopol, Polyacrylicacid,PEG, etc

PVP, etc.

C) According to charge
Charged Uncharged

Aminodextran, Chitosan, Carbopol, Starch, PEG, PVA, PVP, etc.

SodiumAlginate, Pectin, SodiumCMC, etc.

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 Factors affecting mucoadhesion
A)Polymer related factors:
• Molecular weight
• Conc. of polymer
• Flexibility of polymer chains
• Presence of functional group
• Spatial conformation
• Cross linking density
B) Environment related factors:
• pH of polymer substrate interface
• Applied strength
C) Physiological factors:
• Mucinturn over
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• Disease state
 Advantages
-Advantages over other controlled oral controlled release systems by virtue of
prolongation of residence of drug in GIT.
-Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism

Disadvantages

-If MDDS are adhere too tightlgy because it is undesirable to exert too much force
to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system. 23
 Mucoadhesive dosage form
Semisolid
Gels & ointment
Films
Patches

Solid Mucoadhes
Tablets ive
Matrix tablet dosage
Bioadhesive microparticles
form
Bioadhesive inserts

Liquid
Suspensions
Gel forming liquids

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 A) Matrix tablets-(a)Monolithic
(b)two layered tablets
In monolithic mixture of drug + swelling bioadhesive polymer
bidirectional release & outer side coated with impermeable hyrophobic
substances.

In two layered matrix tablets-

Comprises an inner layer based on bioadhesive polymer &an outer non-
bioadhesive layer containing the drug for a bi-directional release but only
local action .
In case of systemic action outer layer is inert & act as a protective layer.

B) Patches-
Greater patient complaince compared with tablets owing to their physical
flexibility that causes only minor discomfort to the patient.

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C) Films-may be preferred over adhesive tablets in terms of
flexibility &comfort.
An ideal film should be flexible,elastic &soft, without
breaking due to stress from mouth movements.

D) Gels & ointments- adv.over other dosage form is that

they are easily dispersion throughtout the mucosa.
But accuracy of drug dosing may not be as accurate.
Certain polymer are used such as NaCMC,
xanthan,carbopol,hyaluronic acid .
They change from liquid to semisolid.
HPMC has been used as an adhesive ointment ingredients.

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 METHODS OF EVALUATION
A) In vitro/ Ex vivo methods B) In Vivo methods
• Methods determining tensile strength • Use of radioisotopes
• Methods determining shear stress • Use of gamma scintigraphy
• Adhesion weight method • Use of pharmacoscintigraphy
• Fluorescent probe method • Use of electron paramagnetic
• Flow channel method resonance
• Mechanical spectroscopic method •(EPR) oximetry
• Filling liquid film method
• Colloidal gold staining method
• Viscometer method
• Thumb method
• Adhesion number
• Electrical conductance
• Swelling properties
• In vitro drug release studies
• Muco retentability studies 27
 Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan
microspheres for the treatment of ulcerative colitis.
Seema Badhana1, Navneet Garud2, *Akanksha Garud

• Mesalamine (5-ASA) is an anti-inflammatory drug used to treat

crohn’s disease and ulcerative colitis.
• Microspheres were prepared by the modified emulsification method
using calcium chloride as cross linking agent. The microspheres were
coated with Eudragit S-100 by the solvent evaporation technique to
prevent drug release in the stomach.

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 References
• Phanindra B, B Krishna (2013) Recent advances in mucoadhesive drug delivery
system: A review. Int. J. Pharm. Med. & Bio. Sc. 1-15.

• Flávia Chiva Carvalho, Marcos Luciano Bruschi (2010) Mucoadhesive drug

delivery systems. Brazilian Journal of Pharmaceutical Sciences.1-9.

• Seema Badhana, Navneet Garud, Akanksha Garud (2013) Colon specific drug
delivery of mesalamine using eudragit S100-coated chitosan microspheres for the
treatment of ulcerative colitis . International Current Pharmaceutical Journal .42-45.

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