Mucoadhesive Drug Delivery System: Miss. Duduskar Anita Ankush
Mucoadhesive Drug Delivery System: Miss. Duduskar Anita Ankush
Mucoadhesive Drug Delivery System: Miss. Duduskar Anita Ankush
seminar
on
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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.
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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
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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
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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
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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
HPMC
Hydroxypropylcellulose
Soluble Insoluble
C) According to charge
Charged Uncharged
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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.
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.
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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
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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.
• 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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