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. 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. 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% 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) Electronic theory Wetting theory Adsorption theory Diffusion theory Fracture theory 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 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

1. (2015-2016)
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.
1

2. • Introduction
• Basics ,concepts & mucosal membrane.
• Need of mucoadhesive DDS
• Mechanism of mucoadhesion
• Theories mucoadhesion
• Sites of mucoadhesionSites of mucoadhesion
• Penetration enhancerPenetration enhancer
• Mucoadhesive polymerMucoadhesive polymer
• Factor affecting mucoadhesionFactor affecting mucoadhesion
• Advantages & DisadvantagesAdvantages & Disadvantages
• Mucoadhesive dosage formMucoadhesive dosage form
• EvaluationEvaluation
• Case studyCase study
• Reference
2

3. • 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.
3

4. • 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.
4

5. - Inner layers called mucosa
- Inner epithelial Cell lining
Covered with viscoelastic fluid.
-Secreted by Goblet cells
-Composed of water and mucin
-Other components include proteins,
lipids and mucopolysaccharides
,electrolytes
-Main role is protective and
lubricates
-Tendency substance to remain
adhered to surface
-If substance adhere to
Biological mucosal layers is
called as Mucoahesion
5

6. 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%
6

7. General structure of mucous layer
7

8. 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.
8

9. Avoidance
of
First pass
Metabolism
Avoidance
of
First pass
Metabolism
Better absorption
of peptide by
penetration enhancer
Better absorption
of peptide by
penetration enhancer
Prolong
residence time
Prolong
residence time
Localization
of drug at
given site
Localization
of drug at
given site
WHY ?
9

10. Mechanisms of mucoadhesionMechanisms 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)
10

11. 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
11

12. 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
12

13. 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
13

14. • Electronic theory
• Wetting theory
• Adsorption theory
• Diffusion theory
• Fracture theory
14

15. 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.
15
3) Adsorption theory
-Surface forces ( covalent bond, ionic bond, hydrogen
bond & van der waals forces) resulting in chemical
bonding

16. 4) Diffusion theory
-Physical entanglement of mucin strands and flexible
polymer chains.
16
5) Fracture theory
-Analyses the maximum tensile stress develop during
detachment of the BDDS from mucosal surfaces

17. Different routes of targeting
MDDS
17

18. 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.
18

19. 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
19

20. Natural and semisynthetic Synthetic
Agarose Carbopol
Chitosan PVA
Gelatin PVP
Pectin Thiolated polymer
CMC Methacrylic acid
Thiolated CMC Polycarbophil
HPMC
Hydroxypropylcellulose

21. Soluble Insoluble
CMC, Sodium CMC, HPMC, MC, PVA,
PVP, etc.
Carbopol, Polyacrylicacid,PEG, etc
C) According to charge
Charged Uncharged
Aminodextran, Chitosan, Carbopol,
SodiumAlginate, Pectin, SodiumCMC, etc.
Starch, PEG, PVA, PVP, etc.
21

22. 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
• Disease state22

23. -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
Advantages
-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.
Disadvantages
23

24. Mucoadhesive dosage form
Mucoadhes
ive
dosage
form
Liquid
Suspensions
Gel forming liquids
Solid
Tablets
Matrix tablet
Bioadhesive microparticles
Bioadhesive inserts
Semisolid
Gels & ointment
Films
Patches
24

25. 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.
25

26. 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.
26

27. METHODS OF EVALUATION
A) In vitro/ Ex vivo methods
• Methods determining tensile strength
• Methods determining shear stress
• Adhesion weight method
• Fluorescent probe method
• Flow channel method
• Mechanical spectroscopic method
• 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
B) In Vivo methods
• Use of radioisotopes
• Use of gamma scintigraphy
• Use of pharmacoscintigraphy
• Use of electron paramagnetic
resonance
•(EPR) oximetry
27

28. 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.
28

29. 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.
29

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