Mucoadhesive Drug Delivery System

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Mucoadhesive drug delivery

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Mucoadhesive 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
a!ecting mucoadhesionFactor a!ecting 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 e!ects.
• 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 a!inity 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 •
Di!usion 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) Di!usion 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. Di!erent 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 a!ecting 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 a"er use,otherwise
the mucosa could be injured. -Some patient su!ers
unpleasent feeling. -Unfortunately ,the lack of standardized
techniques o"en 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
&so", 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
30. 30
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