This document discusses mucoadhesive drug delivery systems, which use bioadhesive polymers that adhere to mucosal membranes to increase drug residence time and bioavailability. It covers the basics of mucosal membranes and theories of mucoadhesion, as well as the mechanisms, types of polymers, formulations, and targets for bioadhesive drug delivery. The goal of these systems is to deliver drugs through mucosal routes and potentially bypass first-pass metabolism through prolonged adhesion to the site of administration.

1. Mucoadesive Drug Delivery
System
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2. CONTENT
• Basics ,concepts & mucosal membrane.
• Theories mucoadhesion
• Mechanisms of Bioadhesion
• Drug Absorption
• Bio(muco)adhesive Polymer
• Types of Bioadhesive Formulations
• Targets for Bioadhesive Formulations
• Oral Bioadhesive Formulations
• Conclusion
• Reference
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3. Muco + adhesive
Inner layers called mucosa Tendency substance
Inner epithelial Cell lining Covered
to remain adhered to
with viscoelastic fluid. surface
Secreted by Goblet cells
Composed of water and mucin (an If substance
anionic polyelectrolyte ) adhere to Biological
Other components include proteins, membrane is called
lipids and mucopolysaccharides as Bioadhesion .
,electrolytes If substance
Thickness varies from ≈40–50 adhere to Biological
μm to ≈300 μm mucosal layers is
called as
Main role is protective and
Mucoahesion.
lubricates
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4. Mucin
Mucin constitute > 95% of water .
Gel like consistency due to glycoproteins
 Chemically oligosacharide chain with terminal
Sialic acid ( pka=2.6)
Mucins are large molecules with molecular
masses ranging from 0.5 to over 20 MDa.
Gastric mucin of Mw ≈10 MDa
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5. Mucosal membranes
These are moist
membranes that line
passageways and
structures in the
body that lead to the
outside environment
such as the mouth,
respiratory tract,
gastrointestinal tract,
nose and vagina
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6.  Bioadhesion is used to describe the bonding or adhesion
between a synthetic or natural polymer and soft tissues
biological substrate such as epithelial cells, which
allows the polymer to adhere to the biological surface for
an extended period of time .
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7. Concept
 The drug can be incorporated into a cross linked
polymer device that would adhere to mucosal membrane in
the body .the drug can diffuse from device directly in the
tissue.
Adhesion ,anchoring of polymer device result in increase
residence time , bioavailability & site specificity.
Decrease in frequency of administration with low dose ,
rate of elimination.
Can bypass Firstpass metabolisum in route is other than oral
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8. Pathway to Bypass
Oral Delivery
Portal Circulation
Pharmacological
Response
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9. Theories mucoadhesion
The phenomena of bioadhesion occurs by a complex
mechanism
There are seven theories have been proposed till date
The Theories include :-
(a) The electronic theory,
(b) The wetting theory,
(c) The adsorption theory.
(d) The diffusion theory,
(e) The mechanical theory
(f) The cohesive theory.
(g) Fracture theory.
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10. The electronic theory
Proposes transfer of electrons amongst the
surfaces due to difference in their electrical structure
resulting in the formation of an electrical double layer
thereby giving rise to attractive forces.
 The wetting theory
Postulates that if the contact angle of liquids
on the substrate surface is lower, then there is a greater
affinity for the liquid to the substrate surface. If two such
substrate surfaces are brought in contact with each other
in the presence of the liquid, the liquid may act as an
adhesive amongst the substrate surfaces.
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11. The adsorption theory
After initial contact of the material adhere to
surface due to forces acting between the atoms in the two
surfaces later result in formation of bonds(primary &
secondary )due to the presence of intermolecular forces,
viz. hydrogen bonding and Van der Waal’s forces, for the
adhesive interaction amongst the substrate surfaces.
The diffusion theory
Assumes the diffusion of the polymer chains,
present on the substrate surfaces, across the adhesive
interface thereby forming a networked , semipermeable
structure. The extent depth to which the polymer chain
penetrate the mucus depend on diffusion coefficient &time of
contact .
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12. The mechanical theory 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.
Surface roughness =d/h
 The cohesive theory proposes that the phenomena of
bioadhesion are mainly due to the intermolecular
interactions amongst like-molecules.
 Fracture theory :-
This theory attempts to relete the difficulty of separation of two
surfaces after adhesion .
Adhesion Strength = (E ԑ/L )1/2
E =Young’s modulus of elasticity
ԑ = Fracture energy
L = Critical crack length when two surfaces are
separated 12

13. Mechanisms of Bioadhesion
 The mechanisms responsible in the formation of bioadhesive bonds are not fully
known, however most research has described bioadhesive bond formation as a
three step process.
Step 1 : Wetting and swelling of polymer
Step 2 : Interpenetration between the polymer chains and the
mucosal membrane
Step 3 : Formation of chemical bonds between the entangled
chains
 Process of bioadhesion can be classified,
1) Chemical (electronic and adsorption theories)
2) Physical (wetting, Diffusion and cohesive theory) 13

14. Step 1
 The wetting and swelling step occurs when the polymer
spreads over the surface of the biological substrate or
mucosal membrane in order to develop an intimate contact
with the substrate.
Bioadhesives are able to adhere to or bond with biological
tissues by the help of the surface tension and forces that
exist at the site of adsorption or contact.
Swelling of polymers occur because the components
within the polymers have an affinity for water.
The image below shows swelling of a polymer
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15. Step 2
 The surface of mucosal membranes are composed of high
molecular weight polymers known as glycoproteins.
 In step 2 of the bioadhesive bond formation, the
bioadhesive polymer chains and the mucosal polymer
chains intermingle and entangle to form semi permeable
adhesive bonds. The strength of these bonds depends on
the degree of penetration between the two polymer groups.
 In order to form strong adhesive bonds, one polymer group
must be soluble in the other and both polymer types must
be of similar chemical structure.
The interpenetration of polymer chains
Bioadhesive
polymer chains
Mucus
polymer chains
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16. Step 3
 This step involves the formation of weak chemical bonds
between the entangled polymer chains.
The types of bonding formed between the chains include
primary bonds such as covalent bonds and weaker
secondary interactions such as van der Waals Interactions
and hydrogen bonds.
 Both primary and secondary bonds are exploited in the
manufacture of bioadhesive formulations in which strong
adhesions between polymers are formed.
Mechanisms of bioadhesion
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17. Types of intecraction Involved
1)Physical And Mechanical.
2)Secondary chemical bond.
3)Ionic,primary or covalent chemical bonds
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18. Drug Absorption
 Drug absorption is the process by which a drug leaves its site of administration
and enters the general circulation
Passive diffusion Facilitated passive diffusion
Active transport Pinocytosis
.
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19. In Bioadhesive Drug Delivery System the drug molecules
Is either dispersed in matrix of polymer or matrix type is
coated with bio(muco)adhesive polymer.
Bio(muco)adhesive Polymer
A bioadhesive polymer is a synthetic or natural
polymer which binds to biological substrates such as
mucosal membranes.
Sometimes referred to as biological ‘glues’
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20. Classification of Bio(Muco)adhesive polymers
A )Based on Specificity :-
1) The specific bioadhesive polymers
Are the ability to adhere to specific chemical structures
within the biological molecules
e.g. lectins, fimbrin
2) The nonspecific bioadhesive polymers
Are the ability to bind with both the cell surfaces and the
mucosal layer.
e.g.polyacrylic acid, cyanoacrylates
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21. B ) Based on Origen
(I) Synthetic polymers:
(a) Cellulose derivatives:-methylcellulose, ethylcellulose,
hydroxy-ethylcellulose, Hydroxyl propyl cellulose, hydroxy
propyl methylcellulose, sodium carboxy methylcellulose.
(b) Poly (acrylic acid) polymers (carbomers, Polycarbophil,
poly(methylacrylate).
(c) Poly (hydroxyethyl methylacrylate).
(d) Poly (ethylene oxide).
(e) Poly (vinyl pyrrolidone).
(f ) Poly (vinyl alcohol).
(II) Natural polymers:
Tragacanth ,Sodium alginate, Karaya gum,
Guar gum ,Xanthan gum ,Lectin ,Soluble starch,
Gelatin, Pectin, Chitosan , Hyaluronic acid .
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22. Relative mucoadhesive performance of some
polymers :-
Polymer Relative Quality of
mucoadhesive force bioadhesion
CMC 193 Excellent
Carbopol 185 Excellent
Tragacanth 154 Excellent
Sod. alginate 126 Excellent
HPMC 125 Excellent
Gelatin 116 fair
Pectin 100 Poor
Acacia 98 Poor
Providone 98 Poor 22

23. Molecular properties of mucoadhesive :-
1. Strong hydrogen bonding groups (-OH, -COOH).
2. Strong anionic charges.(cellulose derivatives) but
some cationic (e.g., Chitosan)
3. Sufficient flexibility to penetrate the mucus network or
tissue crevices.
4. Surface tension characteristics suitable for wetting
mucus/ mucosal tissue surface.
5. High molecular weight.
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24. Characteristics of Bioadhesive polymers
1)Flexibility- important because it controls the extent of the
interpenetration between the polymers and mucosal/epithelial
surfaces.
2)Hydrophilicity – Polymers that are hydrophilic in nature are
able to form strong adhesive bonds with mucosal membranes
because the mucus layer contains large amounts of water.
3)Hydrogen bonding – Hydrogen bonding between the
entangled polymer chains forms strong adhesive bonds,
therefore the presence of hydrogen bond – forming groups such
as OH and COOH groups are vital in large quantities.
4)High molecular weight – Polymers with a high molecular
weight are desirable because they provide more bonding sites.
5)Surface tensions – Surface tensions are needed to spread
the bioadhesive polymer into the mucosal layer epithelial surface.
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25. Characteristics of an ideal mucoadhesive polymer
1. The polymer and its degradation products should be
nontoxic and should be nonabsorable from the
gastrointestinal tract.
2. It should be nonirritant & non abrasive to the mucous
membrane.
3. It should preferably form a strong noncovalent bond
with the mucin-epithelial cell surfaces.
4. It should adhere quickly to most tissue and should
possess some site-specificity.
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26. Continued…
5. It should allow easy incorporation to the drug and offer
no hindrance to its release.
6. The polymer must not decompose on storage or during
the shelf life of the dosage form.
7. The cost of polymer should not be high so that the
prepared dosage form remains competitive.
8.It should get Wash out at desired period.
9.The mucoadhesive should be with high drug-
loading capability.
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27. Factor affecting Mucoadhesion
A)Polymer related :-
1)molecular weight –up to 10 00 000 and beyond this there
is not much effective .
2)Concentration of active polymer –optimum not too high
that significantly drops strength.
3)Flexibility of polymer chain –
4)spatial conformation –
B)Environmental related :-
1)PH
2)Applied strength – increase up to optimum level
3)Initial contact time
4)swelling –too greater decrease the adhesion
5)mucus compossion
C)Physiological factors :-
1)Mucin turn over
5)Diseased state
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28. Delivery Systems
1 )Monolithic (or matrix) systems:-
where the drug is dissolved or dispersed
in the polymer system diffusion of drug from the
drug/polymer matrix controls the overall rate of its
release from the device.
2)Reservoir (or membrane) systems :-
where diffusion resistance across a
polymeric membrane controls the overall drug release
rate.
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29. Types of Bioadhesive Formulations
1.Solid Bioadhesive Formulations :-Tablets , Inserts ,Powders,
,
tapes
2. Semi-solid bioadhesive Formulations:- Gels , Films, solutions,
aerosol sprays
3.Liquid Bioadhesive Formulations:- Viscous liquids ,
Gel-forming liquids
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30. Targets for Bioadhesive Formulations
Body site Systems
Eye Mucoadhesive eye drops / inserts
Nasal cavity Nasal drug delivery systems
Oral cavity Dental gels / buccal systems
Skin Patches, tapes, dressings
Vagina Local vaginal delivery systems
Rectum Local/systemic rectal delivery systems
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31. Oral Bioadhesive Formulations
 Oral bioadhesive formulations are topical products
designed to deliver drugs to the oral cavity which act by
adhering to the oral mucosa and therefore produce
localised effects within the mouth
The oral cavity
Important functions which
include chewing, speaking
and tasting. Some of these
functions are impaired by
diseases such as ulcers,
microbial infections and
inflammation.
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32. In contact with saliva Dosage
form become adhesive and
render system attached to mucosa
Drug solution rapidly absorbed throug the the
reticulated vein which is underneath the oral
mucosa & transported through facial vein ,internal
jugular vein ,Brachiocephalic vein .
Rapid absorption –peak 1to 2 min
Some of the common conditions - Mouth ulcers , Oral thrush,
Gingivitis.
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33. A ) The Buccal Mucosa
The buccal mucosa refers to the
inner lining of the lips and cheeks.
 The epithelium of the buccal mucosa is about 40-50
cells thick and the epithelial cells become flatter as they
move from the basal layers to the superficial layers.
The buccal mucosa is less preferable compared to
other oral drug delivery systems because of vary short
transit time.
The bioadhesive polymers can retention of a dosage
form by spreading it over the absorption site.
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34. B ). The sublingual mucosa
The sublingual mucosa surrounds
the sublingual gland which is a
mucin-producing salivary gland
located underneath the tongue.
Examples :- Glyceryl Trinitrate (GTN) (aerosol spray
(GTN
and tablet in prophylactic treatment of angina.)
Brand name:-Susadrin ,Nitrogard.
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35. 3 ) The Gingival Mucosa
Hardest muscle of body
Can retain dosage form
for long duration
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36. Conclusion
Mucoadhesive dosage forms have a high potential
of being useful means of delivering drugs to the body.Current
use of mucoadhesive polymers to increase contact time for a
wide variety of drugs and routes of administration has shown
dramatic improvement in both specific therapies and more
general patient compliance. The general properties of these
polymers for purpose of sustained release of chemicals are
marginal in being able to accommodate a wide range of
physicochemical drug properties. Hence mucoadhesive
polymers can be used as means of improving drug delivery
through different routes like gastrointestinal, nasal, ocular,
buccal, vaginal and rectal .
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37. Reference
1 )Donald L. Wise ,Handbook of pharmaceutical Controlled Release
Technology
,Marcel Dekker’s Pg .No-168-172255-268.
2)Yie W. Chaine ,NDDS ,Informa Healthcare USA-2009 ,2nd edition ,pg no-
197-229.
3) S. B. Patil*, R. S. R. Murthy, H. S. Mahajan, R. D. Wagh, S. G. Gattani**,”
Mucoadhesive polymers: Means of improving drug delivery” Pharma
Times - Vol 38 - No. 4 - April 2006,pg no -25-28.
4) D r s B h a s k a r a J a s t i , X i a o l i n g L i and G a r y C l e a r y,”
Recent Advances in Mucoadhesive Drug Delivery Systems” B U S I N E S
S B R I E F I N G : P H A R M A T E C H 2 0 0 3,pg no-194-198.
5) S.E. Harding ,” Mucoadhesive interactions” Biochemical Society
Transactions (2003) Volume 31, part 5,pg no-1036-1041.
6) S. Roy1, K. Pal, A. Anis, K.Pramanik and B.Prabhakar“
Polymers in Mucoadhesive Drug Delivery System: A Brief Note “esigned
Monomers and polymers 12(2009),pg no 483-485.
7)Pharmainfonet.com Prof. G.S. Asane “Mucoahhesive anGI DDS ,Vol
5,issu 06,2007.
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38. Thank You
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