Mucoadhesive Drug delivery system, Mucoadhesion, Bioadhesion

1. Mucosal Drug Delivery
system

2. Mucosal Drug Delivery
• Termed as Mucoadhesion or Bioadhesion drug delivery
• bioadhesion implies attachment of a drug carrier system to a specific biological
location.
• If adhesive attachment is to a mucus coat, the phenomenon is referred to as
mucoadhesion.
• Mucoadhesion keeps the delivery system adhering to the mucus membrane.
• Bioadhesion is an interfacial phenomenon in which two materials, at least one
of which is biological, are held together by means of interfacial forces.
• The attachment could be between an artificial material and biological
substrate.

3. Types of Mucoadhesive drug delivery
1. Buccal delivery system
2. Oral delivery system
3. Vaginal delivery system
4. Rectal delivery system
5. Nasal delivery system
6. Ocular delivery system

4. Types of Mucosa

5. Advantages
1. Prolongs the residence time of the dosage form at the site of absorption,
hence increases the bioavailability.
2. Excellent accessibility, rapid onset of action.
3. Rapid absorption because of enormous blood supply and good blood flow
rates.
4. Drug is protected from degradation in the acidic environment in the git.
5. Improved patient compliance.

6. Disadvantages
1. Occurrence of local ulcerous effects due to prolonged contact of the drug
possessing ulcerogenic property.
2. One of the major limitations in the development of oral mucosal delivery
is the lack of a good model for in vitro screening to identify drugs suitable
for such administration.
3. Patient acceptability in terms to taste and irritancy.
4. Eating and Drinking is prohibited

7. Need of Mucoadhesive Delivery
• Prolongation of residence time, drug targeting, intimate contact between
dosage form and the absorptive mucosa.
• Target local disorders at the mucosal surface to reduce dose and to minimize
the side effects.
• Mucoadhesive formulations attract water from the mucosal surface and this
water transfer leads to a strong interaction further increasing the retention
time over the mucosal surfaces and leads to adhesive interactions.
• Prolonged contact time of a drug with a body tissue through the use of a
bioadhesive polymer can significantly improve the performance of many
drugs.

8. MECHANISM OF MUCOADHESION
The mechanism of mucoadhesion between hydrogels and mucosa can be
described in three steps.
1. Wetting and swelling of polymer
2. Interpenetration of the bioadhesive polymer and mucosal membrane.
3. Formation of weak chemical bonds between the entangled chains

9. Composition and application of Mucus layer
Composition of Mucus
1. Mucus is a translucent and viscid
secretion which forms a thin, contentious
gel, mean thickness of this layer varies
from about 50-450 μm in humans
secreted by the globet cells lining the
epithelia.
2. It has the following general composition.
- Water -95%
- Glycoprotein and lipids – 0.5-3.00%
- Mineral salts – 1%
- Free proteins – 0.5-1.0
Applications
1. Protective: resulting particularly from its
hydrophobicity.
2. Barrier: The role of the mucus layer as a
barrier in tissue absorption of the drugs and
influence the bioavailability.
3. Adhesion: Mucus has strong adhesion
properties.
4. Lubrication: It is to keep the mucus from
the goblet cell is necessary to compensate for
the removal of the mucus layer due to
digestion, bacterial degradation and
solubilisation of mucin molecules

11. Factors affecting Mucoadhesion

12. MUCOADHESIVE POLYMERS
1. It must be loaded substantially by the active compound.
2. Swell in the aqueous biological environment of the delivery–absorption
site.
3. Interact with mucus or its components for adequate adhesion.
4. When swelled they allow, controlled release of the active compound.
5. Be excreted unaltered or biologically degraded to inactive, non-toxic
oligomers.
6. Sufficient quantities of hydrogen bonding chemical groups.
7. Possess high molecular weight.
8. Possess high chain flexibility.
9. Surface tension that will induce spreading into mucous layer

13. Classification Mucoadhesive polymer

14. Polymer properties for Mucoadhesion
1. Functional group :functional group such as COOH, OH, NH2, and SO4H may be more favourable as they
interact with mucus not only through physical entanglement but also through chemical bonds, resulting in
formation of cross linked network.
2. Degree of hydration Hydration:. Excess of hydration could lead to decreased mucoadhesion and/or
retention due to the formation of a slippery mucilage. cross-linked polymers that only permit a certain
degree of hydration may be advantageous for providing a prolonged mucoadhesive effect.
3. Chain length : Increased chain mobility leads to increased inter diffusion and interpenetration of the
polymer within the mucus network. Long polymer chains lose their ability to diffuse and interpenetrate
through mucosal surfaces. Hence as the chain length decreases interpenetration increases
4. Degree of cross linking : The chain mobility and resistance to dissolution is significantly influenced by the
degree of cross-linking within a polymer system. Cross-linked hydrophilic polymers swell in the presence of
water allowing them to retain their structure. High molecular weight linear hydrophilic polymers are
swellable and readily dispersible.

15. 5. Polymer concentration : Polymer concentration is dependent on physical state of the delivery system. In the
semisolid state, polymer concentration is low which reduces adhesion. Hence lower number of polymer chains
are available for interpenetration with mucus. On the other hand, solid dosage forms such as buccal tablets
exhibit increased adhesive strength as the mucoadhesive polymer concentration increase.

16. Measurement of Bioadhesion
• Depending on the direction in which the mucoadhesive is separated
from the substrate, is it possible to obtain the detachment, shear,
and rupture tensile strengths

17. MEASUREMENT OF DETACHMENT FORCE
• The measure the force required to break the
adhesive bond between a model membrane and the
test polymers.
• Instruments employed: modified balance or tensile
testers

18. MECHANICAL SPECTROSCOPIC METHOD
• Can be used to investigate the interaction between the bioadhesive materials and mucin
• Can be used to study the effect of pH and chain length
• But this method shows a very poor correlation with in vivo bioadhesion
ELECTRICAL CONDUCTANCE METHOD
• Equipment: modified rotational viscometer capable of measuring electrical conductance
• Electrical conductance as a function of time is measured
• In presence of adhesive material, the conductance is low

19. THUMB TEST
• It is a simple test to identify if the material is mucoadhesive
• The adhesiveness is quantitatively measured by the difficulty of pulling the adhesive from the thumb as a
function of pressure and contact time.
• This test can be used as most mucoadhesives are not mucin specific
• It is not a conclusive test but gives useful information on mucoadhesive potential

20. EVERTED GUT SAC OF RATS Method
• A segment of intestinal tissue is removed from the rat, everted, and one of its ends sutured and
filled with saline.
• The sacs are introduced into tubes containing the system under analysis at known concentrations,
stirred, incubated and then removed.
• The percent adhesion rate of the release system onto the sac is determined by subtracting the
residual mass from the initial mass

21. Viscosity measurement
• Viscosities of mucin dispersion can be measured by Brookfield viscometer
• Viscosity can be measured in absence or presence of bioadhesive material
• Viscosity components can give an idea about force of biodahesion
• The energy of the physical and chemical bonds of the mucin-polymer interaction can be transformed into
mechanical energy or work.
• This work, which causes the rearrangements of the macromolecules, is the basis of the change in viscosity.
GI transit study using radio-opaque markers
• It is a simple procedure involving the use of radio-opaque markers, e.g. barium sulfate, encapsulated in
bioadhesive to determine the effectss of bioadhesive polymers on GI transit time.
• Faeces collection (using an automated faeces collection machine) and X-ray inspection provide a non-invasive
method of monitoring total GI residence time without affecting normal GI motility.

22. In Vivo Methods
• Use of radioisotopes
• Use of gamma scintigraphy
• Use of pharmacoscintigraphy
• Use of electron paramagnetic resonance(EPR) oximetry
• X ray studies
• Isolated loop technique

23. Applications of Mucoadhesive drug delivery
1. Buccal drug delivery :
 high accessibility and low enzymatic activity
 Can be terminated in cases of toxicity through the removal of dosage.
 polymers such as sodium carboxymethylcellulose, hydroxypropylcellulose and polycarbophil are used for
delivery of peptides, protein and polysaccharides
 Ex:tablets, patches and films
2. Ophthalmic drug delivery :
 Dosage form include liquid drops, gels, ointments and solid ocular inserts
 polymers would be expected only to attach to conjunctival mucus
 carbomer and polycarbophil are used because of the high swelling capacity of and neutral pH environment of
the eye

24. 3. Vaginal drug delivery systems :
 Avoidance of hepatic first-pass metabolism .
 Promising site for systemic drug delivery because of its large surface area, rich blood supply and high
permeability .
 Residence times within the vagina tend to be much higher than at other absorption sites such as the rectum or
intestinal mucosa.
 Vaginal formulations include polycarbophil, hydroxypropylcellulose and polyacrylic acid
4. Nasal drug delivery
 provides a large highly vascularised surface area through which first-pass metabolism can be avoided
 solutions, powders, gels and microparticles are used for nasal delivery.
 intranasal active ingredient are solutions containing sympathomimetic vasoconstrictors for immediate relief of
nasal congestion.