Mucoadhesive drug delivery systems interact with mucus and increase the residence time of dosage forms at the site of absorption. They are part of controlled delivery systems and can target drugs to specific sites, avoiding first-pass metabolism. The mechanisms of mucoadhesion involve contact and consolidation stages, where mucoadhesive molecules form bonds with mucus glycoproteins. Key factors that impact mucoadhesion include molecular weight, flexibility, crosslinking density, hydrogen bonding capacity, hydration, and polymer concentration. Common sites for these systems are the oral cavity, eye, vagina, nose, and gastrointestinal tract.

1. Mucoadhesive Drug Delivery System
Deepa Guruwacharya
Deepak Dhami
Harish Kumar Jyoti
Kamala Pardhan

2. Mucous membrane
• Mucous membrane or mucosa is a membrane that line various cavities in the
body and covers the surface of internal organs.
• Mucous membranes (the mucosa) have moist surfaces lining the walls of the
organs of the gastrointestinal tract and respiratory passages, the inner part of
the eyes, as well as the nasal and oral cavities and the genital organs.

3. 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. Mechanisms of mucoadhesive
• The mechanism of mucoadhesion is generally divided into two steps: the
contact stage and the consolidation stage.
• The first stage is characterized by the contact between the mucoadhesive and
the mucus membrane, with spreading and swelling of the formulation,
initiating its deep contact with the mucus layer.
• In the consolidation step the mucoadhesive materials are activated by the
presence of moisture. Moisture plasticizes the system, allowing the
mucoadhesive molecules to break free and to link up by weak van der Waals
and hydrogen bonds.

5. Mechansims of mucoadhesive
• Essentially, there are two theories explaining the consolidation step: the
diffusion theory and the dehydration theory.
• According to the diffusion theory, the mucoadhesive molecules and the
glycoproteins of the mucus mutually interact by means of interpenetration of
their chains and the building of secondary bonds.
• For this to take place, the mucoadhesive device has features favoring both
chemical and mechanical interactions.
• For example, molecules with hydrogen bond building groups (–OH, –
COOH), an anionic surface charge, high molecular weight, flexible chains
and surface-active properties, which help in spreading throughout the mucus
layer, can present mucoadhesive properties.

6. MUCOADHESIVE DRUG DELIVERY
SYSTEM
Advantages
• Targeting and localization of the dosage
form at a specific site.
• Avoid of first pass metabolism.
• Painless administration.
• Excellent accessibility.
Disadvantages
• Some patients suffers unpleasant felling's.
• Costly drug delivery system.
• Due to lack of standardized techniques
often leads to unclear results.

7. Theories of mucoadhesion
• Electronic theory
• Wetting theory
• Adsorption theory
• Diffusion theory
• Fracture theory

8. Theories of mucoadhesion
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

9. Theories of mucoadhesion
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.

10. Sites for Mucoadhesive Drug Delivery Systems
The common sites of application where mucoadhesive polymers have the ability
to deliver pharmacologically active agents include oral cavity, eye conjunctiva,
vagina, nasal cavity and GIT.

11. 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
• E.g.. Benzalkonium chloride , Dextran sulfate ,Fatty acid ,
Propylene glycol, Men ,Sodium EDTA etc.

12. 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
• Nonirritant to mucous membrane
• Form a strong non-covalent bond with mucin epithelial cell surface

13. POLYMERS CLASSIFICATION
• According to their source
Agarose Carbopol
Gelatin PVA
Pectin PVP
CMC Thiolated polymer
HPMC Methacrylic acid
Thiolated CMC Polycarbophil
Hydroxypropyl cellulose
Natural &
Semisynthetic
Synthetic

14. POLYMERS CLASSIFICATION
• According to water solubility
Soluble Insoluble
CMC Carbopol
Sodium CMC Polyacrylic acid
HPMC PEG
PVA, PVP

15. POLYMERS CLASSIFICATION
• According to charge
Charged Uncharged
Amino dextran Starch
Chitosan PEG
Sodium Alginate PVA
Sodium CMC PVP

16. Mucoadhesive Dosage Forms
1.Solid
Tablets
Matrix tablets
Bioadhesive microparticles
Bioadhesive inserts
2.Semisolid
Gels & ointment
Films
Patches
3.Liquid
Suspensions
Gel forming liquids

17. Mucoadhesive Dosage Forms
A. Matrix tablets
a. In monolithic: mixture of drug + swelling bioadhesive polymer bidirectional
release & outer side coated with impermeable hyrophobic substances.
b. 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.

18. Mucoadhesive Dosage Forms
B. Patches : Greater patient compliance compared with tablets owing to their
physical flexibility that causes only minor discomfort to the patient.
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: advantage 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.

19. METHODS OF EVALUATION
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

20. In vivo methods
• Use of radioisotopes
• Use of gamma scintigraphy
• Use of pharmacoscintigraphy
• Use of electron paramagnetic resonance
• (EPR) oximetry

21. Factors affecting mucoadhesion
1. Molecular weight
The mucoadhesive strength of a polymer increases with molecular weights
above 100,000. Direct correlation between the mucoadhesive strength of
polyoxymethylene polymers and their molecular weights lies in the range of
200,000–7,000,000.
2. Flexibility
Mucoadhesion starts with the diffusion of the polymer chains in the interfacial
region. Therefore, it is important that the polymer chains contain a substantial
degree of flexibility in order to achieve the desired entanglement with the
mucus.

22. Factors affecting mucoadhesion
3. Cross-linking density
The average pore size, the number and average molecular weight of the cross-
linked polymers, and the density of cross-linking are three important and
inter-related structural parameters of a polymer network. Therefore, it seems
reasonable that with increasing density of cross-linking, diffusion of water
into the polymer network occurs at a lower rate which, in turn, causes an
insufficient swelling of the polymer and a decreased rate of interpenetration
between polymer and mucin.

23. 4. Hydrogen bonding capacity
Hydrogen bonding is another important factor in mucoadhesion of a polymer.
Desired polymers must have functional groups that are able to form hydrogen
bonds, and flexibility of the polymer is important to improve this hydrogen
bonding potential. Polymers such as poly(vinyl alcohol), hydroxylated
methacrylate, and poly(methacrylic acid), as well as all their copolymers,
have good hydrogen bonding capacity.

24. 5. Hydration
Hydration is required for a mucoadhesive polymer to expand and create a proper
macromolecular mes of sufficient size, and also to induce mobility in the polymer
chains in order to enhance the interpenetration process between polymer and mucin.
Polymer swelling permits a mechanical entanglement by exposing the bioadhesive
sites for hydrogen bonding and/or electrostatic interaction between the polymer and
the mucus network. However, a critical degree of hydration of the mucoadhesive
polymer exists where optimum swelling and mucoadhesion occurs.

25. 6.Concentration
The importance of this factor lies in the development of a strong adhesive bond with the mucus,
and can be explained by the polymer chain length available for penetration into the mucus
layer. When the concentration of the polymer is too low, the number of penetrating polymer
chains per unit volume of the mucus is small and the interaction between polymer and mucus
is unstable. In general, the more concentrated polymer would result in a longer penetrating
chain length and better adhesion. However, for each polymer, there is a critical concentration,
above which the polymer produces an “unperturbed” state due to a significantly coiled
structure. As a result, the accessibility of the solvent to the polymer decreases, and chain
penetration of the polymer is drastically reduced.

26. Evaluation tests of muco-adhesive tablets
• Weight variation
• Friability
• Hardness
• Content uniformity
• Drug release study of Mucoadhesive tablets
• Swelling index
• Water sorption studies
• Mucoadhesive strength

27. References
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255397/
• https://www.slideshare.net/anitaduduskar/mucoadhesive-drug-delivery-
system-59757914