In this presentation I have mentioned whatever the possible relevant content required for the Mucoadhesive drug delivery system. Citation Is done at the end of slide. Content is up to date & true to my belief. Thanks & Best Regards. Anurag Pandey B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY) M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY) Email :- anurag.dmk05@gmail.com

1. 1
MUCOADHESIVE
DRUG DELIVERY SYSTEM
Presented by :-
Anurag Pandey
M.Pharm (Pharmaceutics)
17mph101
Under the guidance of :-
Dr. Dhaivat Parikh
Asst. Professor
Institute of Pharmacy, Nirma University

2. INTRODUCTION
WHY MDDS?
GENERAL COMPOSITION OF MUCUS
THEORIES OF MUCO-ADHESIVE
MECHANISM OF MUCO-ADHESION
MUCO-ADHESIVE POLYMER
DIFFERENT ROUTES OF TARGETING MDDS
FORMULATION DESIGN
MUCO-ADHESIVE DOSAGE FORM
METHODS OF EVALUATION
FACTOR AFFECTING MUCO-ADHESION
ADVANTAGES & DISADVANTAGES
CONCLUSION
REFERENCES
FLOW OF PRESENTATION

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.
QUESTION: - HOW RESIDENCE TIME INCREASE?
Comment: - 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.
INTRODUCTION

4.  Adhesion of polymer device result in increased residence time,
bioavailability & site specificity & as well it decreases in frequency
of administration with low dose , rate of elimination.
 Mucoadhesive drug delivery system is a part of controlled delivery
system.
 Hydrophilic high mol. wt. such as peptides that cannot be
administered & poor absorption, then MDDS is best choice.
CONT…

5. CONT…
MUCO
1. Inner layers called mucosa
2. Inner epithelial Cell lining Covered with
viscoelastic fluid.
3. Secreted by Goblet cells
4. Composed of water and mucin (an
anionic polyelectrolyte)
5. Other components include proteins,
lipids and mucopolysaccharides ,
electrolytes
6. Main role is protective and lubricates
ADHESIVE
1. Tendency substance to remain
adhered to surface.
2. If synthetic or natural polymer
adheres to Biological membrane
(epithelial cells) which allows the
polymer to adhere to the biological
surface for an extended period of time
is called as Bio-adhesion
3. If substance adhere to Biological
mucosal layers is called as Muco-
adhesion.

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

7.  Water…………………………………………..95% (More than 95%)
 Glycoprotein and lipids……………………..0.5-5% (Due to which gel like str.
Usually seen & surface of mucosal membranes are composed of high molecular
weight polymers known as glycoproteins)
 Mineral salts…………………………….…..…1%
 Free proteins……………………………….…..0.5-1%
 Thickness varies from 40 μm to 300 μm
GENERAL COMPOSITION OF MUCUS

8. Chemically oligosaccharide 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
Function of Mucus Membrane
Protective
Barrier
Adhesion
Lubrication
CONT…

9. There are seven theories have been proposed till date :-
1. The electronic theory,
2. The wetting theory,
3. The adsorption theory.
4. The diffusion theory,
5. The mechanical theory
6. The cohesive theory.
7. Fracture theory.
THEORIES OF MUCOAHESIVE DELIVERY

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.
CONT..

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 of
semipermeable structure. The extent depth to which the polymer chain
penetrate the mucus depend on diffusion coefficient & time of contact .
CONT..

12. The mechanical theory
 It 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
 It proposes that the phenomena of bio-adhesion are mainly due to the
intermolecular interactions amongst like-molecules.
CONT…

13. Fracture theory :-
 This theory attempts to relate the difficulty of separation of two
surfaces after adhesion.
Adhesion Strength =
𝐸 ∗
𝜀
𝑙
E =Young’s modulus of elasticity
ԑ = Fracture energy
L = Critical crack length when two surfaces are separated
CONT…

14. MECHANISM OF MUCOADHESION
Wetting and swelling of the
polymer(contact stage)
Interpenetration between the
polymer chains and the mucosal
membrane
Formation of bonds between the
entangled chains
(both known as consolidation stage)
STAGE -I
STAGE-II
STAGE-III

15. They are water soluble and water insoluble polymers
which forms swellable networks
joined by cross linking agent &
Sometimes referred to as biological ‘Glues’.
MUCOADHESIVE POLYMER

16. 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
Relative Muco-adhesive
performance of some polymers

17. CHARACTERISTICS OF AN IDEAL
MUCOADHESIVE POLYMER
1 The polymer and its degradation products should be nontoxic and
should be non-absorbable from the gastrointestinal tract.
2 It should be nonirritant & non-abrasive to the mucous membrane.
3 It should preferably form a strong non-covalent bond with the mucin-
epithelial cell surfaces.
4 It should adhere quickly to most tissue and should possess some site-
specificity.
5 Surface tensions

18. CONT…
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 muco-adhesive should be with high drug-loading capability.

19. POLYMER CLASSIFICATION
A) Based on Specificity
Specific bio-adhesive polymers
ability to adhere to specific chemical
structures within the biological
molecules
lectins
fimbrin
Non-specific bio-adhesive polymers
Are the ability to bind with both the
cell surfaces and the mucosal layer
polyacrylic acid
Cyanoacrylates

20. CONT…
B- According to
their source
Natural and
semisynthetic
Chitosan
Agarose
Gelatin
Pectin
CMC,HPMC
Synthetic
Carbopol
PVA,PVP
Meth acrylic
acid
Poly
carbophil

21. DIFFERENT ROUTES OF TARGETING MDDS
MDDS
Rectal
DDS
Vaginal
DDS
Ocular
DDS
Nasal
DDS
Bucca
l DDS
Sublin--
gual
DDS
GI
Tract

22.  In case of both mucosal (local) & trans mucosal (systemic) adm.,
conventional dosage are not able to assure therapeutic level.
 In MDDS contain the following functional agents-
1. Mucoadhesive agents
2. Penetration enhancers
3. Enzyme inhibitors
FORMULATION DESIGN

23. 1. MUCOADHESIVE AGENTS
 The polymer hydration & consequently the mucus cohesive properties that
promote muco-adhesion. Swelling should favour polymer chain flexibility &
interpenetration b/w polymer & mucin chains.
Ex -Polyacrylic acid (PAA), Polyvinyl alcohol (PVA), Sodium
carboxymethylcelluose (NaCMC), Sodium alginate, HPMC, HEC, HPC
 Various copolymer of acrylic acid, polyethylene glycol mono-methyl ether
copolymer have also been studied.
CONT…

24. 2. PENETRATION ENHANCERS (PE)
 PE is also required when a drug has to reach the systemic circulation to
exert its action.
 Must be non-irritant & have a reversible effect.
 Recently chitosan & its derivatives, polymers already known for MA
properties. Chitosan help transportation of drug throw paracellular
pathway.
CONT…

25. E.g., of Permeation Enhancer :-
 Benzalkonium chloride, Dextran sulfate ,Fatty acid, Propyleneglycol, Menthol,
Phosphatidylcholine, Polysorbate 80, Sodium EDTA
3. ENZYME INHIBITORS
 Drug + enzyme inhibitors  Improving the buccal absorption of drugs particularly
peptides.
E.g., Aprotinin, Bestatin, Puromycin
 Bile salts stabilize protein drugs by different mechanism (effecting the activity of the
enzymes, altering the conformation of the protein.
 Chemical modification of chitosan with EDTA produces polymer conjugate chitosan –
EDTA that is a very potent inhibitor of metallopeptidases (carboxypeptidase)
CONT…

26. MUCOADHESIVE DOSAGE FORM
Semisolid
Gels & ointment
Films
Patches
Solid
Tablets
Matrix tablet
Mucoadhesive micro
particles /microsphere
Bioadhesive inserts
Liquid
Suspensions
Gel forming liquids
MUCOADHESIVE
DOSAGE FORM

27.  Particle Size and Shape
Light microscopy (LM) and scanning electron microscopy (SEM).
 Surface Characterization of The Mucoadhesive Microspheres
Data from the SEM, provides insight to the surface morphology of microspheres.
 Surface Charge Study
From photon correlation spectroscopy data the surface charge (zeta potential) of the
Mucoadhesive microspheres can be determine
 Entrapment Efficiency
% Entrapment = Actual content/Theoretical content x 100
METHODS OF EVALUATION

28.  Swelling Index
% swelling = weight of dried microsphere - weight of swelled microsphere/weight of swelled
microsphere × 100
 In- Vitro Release Study
Standard IP/BP/USP dissolution apparatus is used to study in-vitro release.
 Ex-Vivo Muco-adhesion Study
The Mucoadhesive property of the microspheres is evaluated on goat’s intestinal mucosa by
using phosphate buffer, as per monograph.
CONT…

29. 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 compassion
C) PHYSIOLOGICAL FACTORS :-
1) Mucin turns over
2) Diseased state
FACTOR AFFECTING MUCO-ADHESION

30. 30
1. Prolongation of residence of drug in GIT.
2. Targeting & localization of the dosage form at a specific site
3. Painless administration.
4. Low enzymatic activity & avoid of first pass metabolism
Advantages
1. Drug , which irritate the oral mucosa ,have a bitter
or unpleasant taste ,odor cannot be administer by
this route.
2. Some patient suffers unpleasant feeling.
3. Costly drug delivery system.
Disadvantages
04/05/201630

31. Mucoadhesive dosage forms have a high potential of being useful
means of delivering drugs to the body. Current use of muco-adhesive
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 muco-adhesive polymers
can be used as means of improving drug delivery through different
routes like gastrointestinal, nasal, ocular, buccal, vaginal and rectal .
CONCLUSION

32. REFERENCES
Yadav Vimal K.,Kumar Brajesh,Prajapati S.K.,shafaat Kausar,
Design and evaluation of Mucoadhesive microspheres of
repaglinide for oral controlled release,Published by International
Journal of Drug Delivery 3 (2011) 357-370, ISSN: 0975-021.
Nazir Imran, Bashir Sajid et al, Development and Evaluation of
Sustained Release Microspheres of Repaglinide for Management of
Type 2 Diabetes Mellitus,Published By, Journal of Pharmacy and
Alternative Medicine, Vol 1, 2012, ISSN 2222-4807

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