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1. Mucoadhesive drug delivery system
Ravish Yadav

2. • INTRODUCTION
• Since the early 1980,the concept of Mucoadhesion has gained
considerable interest in pharmaceutical technology.
• The strategies studied to overcome such obstacles include the
employment of the materials that, possibly, combine mucoadhesive ,
enzyme inhibitory & penetration enhancer properties & improve the
patient compliance.
• MDDS have been developed 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.
2

3. 3
What is Mucoadhesive drug delivery system?
•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.

4. Why are we using Mucoadhesive drug delivery system(MDDS)?
• MDDS prolong the residence time of the dosage form at the site of
application or absorption.
• Intimate contact of the dosage form with the underlying absorption .
• Improve the therapeutic performance of drug.
• Should not cause irritation.
• High drug loading capacity.
• Controlled drug release(preferably unidirectional
release).
4

5. Types of Drug delivery systems:
Depending upon the route of administration of the mucoadhesive drugs they
are different types .They are
1)Buccal delivery system
2)Sub lingual delivery system
3)Vaginal delivery system
4)Rectal delivery system
5)Nasal delivery system
6)Ocular delivery system
7)Gastro intestinal delivery system 5

6. ADVANTAGES-
• MDDS offer several 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.
• High drug flux at the absorbing tissue.
• MDDS will serve both the purposes of sustain release &
presence of dosage form at the site of absorption.
• Excellent accessibility.
• Painless administration.
• Low enzymatic activity & avoid of first pass metabolism.
6

7. DISADVANNTAGES-
• If MDDS are adhere too tightly because it is undesirable to
exert too much force to remove the formulation after use,
otherwise the mucosa could be injured.
• Some patient suffers unpleasant feeling.
• Unfortunately ,the lack of standardized techniques often leads
to unclear results.
• costly drug delivery system.
• Medications administered orally do not enter the blood stream
immediately after passage through the buccal mucosa.
7

8. COMPOSITION OF MUCUS LAYER:
‘Mucus is translucent and viscid secretion which forms a thin
continuous gel adherent to mucosal epithelial surface.’
• Water - 95%
• Glycoprotein and lipids - 0.5-5%
• Mineral salts - 1%
• Free proteins - 0.5-1%
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9. 9
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

10. 1010
 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 .

11. 11
Concept
11
 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 First pass metabolism in route is other than oral

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Pharmacological
Response
Oral Delivery
Portal Circulation
Pathway to Bypass

13. Theories of mucoadhesion
 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.
The phenomena of bioadhesion occurs by a complex
mechanism .There are seven theories have been
proposed till date

14. 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.

15. 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.
15

16. 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 .

17. 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

18. Cohesive theory :proposes that the phenomena of bioadhesion are mainly due to
the intermolecular interactions amongst like-molecules.
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

19. 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.
hydrogen bonding and Van der Waal’s forces, for the adhesive
interaction amongst the substrate surfaces.
19

20. 2020
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)

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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

22. 22
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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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

24. 24
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

25. Types of interaction Involved
1)Physical And Mechanical.
2)Secondary chemical bond.
3)Ionic, primary or covalent chemical bonds
25

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Drug Absorption
 Drug absorption is the process by which a drug leaves its site of administration and
enters the general circulation
Pinocytosis.
Passive diffusion Facilitated passive diffusion
Active transport

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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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2) The nonspecific bioadhesive polymers
Are the ability to bind with both the cell surfaces and the mucosal layer.
e.g. Polyacrylic acid, cyanoacrylates
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

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(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).
B ) Based on Origen
(II) Natural polymers:
Tragacanth ,Sodium alginate, Karaya gum,
Guar gum ,Xanthan gum ,Lectin ,Soluble starch,
Gelatin, Pectin, Chitosan , Hyaluronic acid .

30. 30
Relative mucoadhesive performance of some
polymers :-
Polymer Relative
mucoadhesive force
Quality of
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
Povidone 98 Poor

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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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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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Characteristics of an ideal mucoadhesive polymer
1. The polymer and its degradation products should be
nontoxic and should be nonabsorbable 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.

34. 3434
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.
Continued…
9.The mucoadhesive should be with high drug-loading capability.

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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

36. 36
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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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.

38. 38
In contact with saliva Dosage form become adhesive and
render system attached to mucosa
Drug solution rapidly absorbed through 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.

39. 3939
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.
A ) The Buccal Mucosa

40. 4040
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 and tablet in prophylactic
treatment of angina.)
Brand name:-Susadrin ,Nitrogard.

41. 41
3 ) The Gingival Mucosa
Hardest muscle of body
Can retain dosage form
for long duration

42. TECHNIQUES FOR EVALUATING BIOADHESIVE
PROPERTIES

43. Techniques utilizing gut sac of rats
• A segment of intestinal tissue is
removed from the rat, everted, and
one of its ends sutured and filled
with saline. The sacs are
introduced into tubes containing
the system under analysis at known
concentrations, stirred, incubated
and then removed. The percent
adhesion rate of the release system
onto the sac is determined by
subtracting the residual mass from
the initial mass
43

44. Tests measuring mucoadhesive strength
44

45. Rupture tensile strength
•Generally, the equipment used is
a texture analyzer or a universal
testing machine. In this test, the
force required to remove the
formulation from a model
membrane is measured, which
can be a disc composed of
mucin, a piece of animal mucous
membrane, generally porcine
nasal mucus or intestinal mucus
from rats.
45

46. Shear strength.
• This test measures the force
required to separate two parallel
glass slides covered with the
polymer and with a mucus film
(Bruschi, Freitas, 2005; Chowdary,
Rao, 2004). This can also be done
using Wilhemy’s model.
• In which a glass plate is suspended
by a microforce balance and
immersed in a sample of mucus
under controlled temperature. The
force required to pull the plate out
of the sample is then measured
under constant experimental
conditions
46

47. • Wilhemy’s plate technique, or the microforce balance technique, can also
be modified in order to measure the specific adhesion force of
microparticles (Chowdary, Rao, 2004; Hägerström, 2003). This involves the
use of a micro tensiometer and a microforce balance (Figure 10) and is
specific, yielding both contact angle and surface tension. The mucous
membrane is placed in a small mobile chamber with both pH and
physiological temperature controlled. A unique microsphere is attached
by a thread to the stationary microbalance. The chamber with the mucous
membrane is raised until it comes into contact with the microsphere and,
after contact time, is lowered back to the initial position
47

48. Shear stress measurement: The
shear stress technique measures the force that causes a mucoadhesive
to slide with respect to the mucous layer in a direction parallel to their
plane of contact .
oAdhesion tests based on the shear stress measurement involve two
glass slides coated with polymer and a film of mucus.
oMucus forms a thin film between the two polymer coated slides, and
the test measures the force required to separate the two surfaces
48

49. Rheological methods
• From this test, it is possible to obtain the mucoadhesion force by
monitoring the viscosimetric changes of the system constituted by the
mixture of the polymer chosen and mucin. The energy of the physical and
chemical bonds of the mucin-polymer interaction can be transformed into
mechanical energy or work. This work, which causes the rearrangements
of the macromolecules, is the basis of the change in viscosity
49

50. Tests analyzing molecular interactions
involved in mucoadhesion
• The general problem arising from methods that show the
adhesion force and from the rheological methods is that the
mucoadhesive response is seen macroscopically while the
interactions occur at a microscopic level.
• The use of low frequency dielectric spectroscopy represents
an attempt to study gel-mucus interactions near the
molecular level. It evaluates the possible physicochemical
interactions between molecules and glycoproteins of the
mucus at the interface, which is considered the step
preceding the formation of bonds during the mucoadhesion
process.
50

51. •This technique involves the study of material response
to the application of an electrical field. A sinusoidal
voltage is applied throughout the sample and the
response is measured in function of the frequency.
From the responses, the impedance or permittivity of
the sample is obtained and the property of charges
changing in the system can be determined.
•Since the mucoadhesion process can be a
consequence of interactions between the mucus layer
and the mucoadhesive polymer, it is highly dependent
upon the molecular structure, including its charge.
51

52. Imaging methods
•Atomic force microscopy (AFM) is a relatively new
technique. It enlarges more than 109-fold, which
enables visualization of isolated atoms and offers a
tridimensional image of the surface.
•The equipment has a support combined with a
probe perpendicularly attached to it. This tip moves
toward a plane parallel to the sample, acquiring its
topographic characteristics and the tip position is
recorded by an optic deflection system: a laser
beam is reflected onto the support and its position
is then further reflected by a mirror reaching a
photodiode sensor.
52

53. • A force-distance curve is plotted to measure the forces between this tip and
the surface of interest. This curve is then used in bioadhesion studies.
53

54. INVIVO TECHNIQUES
GI transit using radio-opaque technique:It involves the use of radio-opaque
markers, e.g., barium sulfate, encapsulated in bioadhesive DDS to determine the
effects of bioadhesive polymers on GI transit time.
Faeces collection (using an automated faeces collection machine) and x-ray
inspection provide a non-invasive method of monitoring total GI residence time
without affecting normal GI motility.
Mucoadhesives labelled with Cr-51, Tc-99m, In-113m, or I-123 have been used to
study the transit of the DDS in the GI tract .
Gamma scintigraphy technique:It is a valuable tool used in the development of
pharmaceutical dosage forms.
With this methodology, it is possible to obtain information non-invasively.

55. oThis technique gives information in terms of:
o oral dosage forms across the different regions of GI tract
othe time and site of disintegration of dosage forms
othe site of drug absorption
oalso the effect of food
odisease
osize of the dosage form on the in vivo performance of the dosage forms.

56. 5656
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 .

57. 5757
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.