NDDS notes- Mucoadhesive drug delivery system B.pharma 4th yr 7th Semester

Mucoadhesive drug delivery system interact with the mucous layer covering the mucosal epithelial surface and mucin molecules and increase the residence time of the dosage form at site of absorption.
Mucoadhesive drug delivery system interact with the mucous layer covering the mucosal epithelial surface and mucin molecules and increase the residence time of the dosage form at site of absorption.
Mucoadhesive drug delivery system interact with the mucous layer covering the mucosal epithelial surface and mucin molecules and increase the residence time of the dosage form at site of absorption.
Attached or Immobolized drug delivery system
These system are being formulated to be remained attached on the mucosal surface by the adhesive properties. These system is also known as mucoadhesive system.
Eg- Buccal drug delivery system, rectal drug delivery system, vaginal drug delivery system, nasal drug delivery system
Different stages have been adopted for controlled mucosal drug delivery system.
The term bioadhesion describes the material that bind or adhere to be biological membrane.
Bioadhesive can be defined as a material that is capable of interacting with biological material and being retained on them or holding them together for long period of time.
Bioadhesion may occur in 3 ways.
Bioadhesion in between biological layers without involvement of artificial materials.
Cells adhesion into culture dishes or adhesion of variety of substances such as wood, metals and other synthetics substances.
Adhesion of artificial substances to the biological substrates like adhesion of hydrophilic polymers to skin and other tissue.

Polymers used in mucoadhesive drug delivery system.

1. NDDS B.Pharm7
th
sem
By Manish Singh
Assistant Professor
Saicollegeof
pharmacy

2. Mucoadhesive drug delivery
system
Mucoadhesive drug delivery system interact with the mucous layer
covering the mucosal epithelial surface and mucin molecules and
increase the residence time of the dosage form at site of
absorption.
Types of mucosal drug delivery systems:
1.Non-attached mucosal delivery systems:
This system are being formulated to be absorbed through the
mucosa with the oral cavity
Example-Sublingual tablet, Fast dissolving tablet etc

3. Attached or Immobolizeddrug
delivery system
These system are being formulated to be remained attached on the
mucosal surface by the adhesive properties. These system is also
known as mucoadhesive system.
Eg-Buccal drug delivery system, rectal drug delivery system, vaginal
drug delivery system, nasal drug delivery system

5. Different stages have been adopted
for controlled mucosal drug delivery
system
Prolonging solely the duration of absorption process.
Developing the unidirectional delivery system.
Preparing user friendly mucosal delivery system.

6. Bioadhesion/ Mucoadhesion.
The term bioadhesiondescribes the material that bind or adhere to be biological
membrane.
Bioadhesivecan be defined as a material that is capable of interacting with
biological material and being retained on them or holding them together for
long period of time.
Bioadhesionmay occur in 3 ways.
Bioadhesionin between biological layers without involvement of artificial
materials.
Cells adhesion into culture dishes or adhesion of variety of substances such as
wood, metals and other synthetics substances.
Adhesion of artificial substances to the biological substrates like adhesion of
hydrophilic polymers to skin and other tissue.

7. Polymers used in mucoadhesive
drug delivery system.
Synthetics polymer-
A)-Cellulose derivatives-Methyl cellulose(MC), Hydroxy ethyl
cellulose(HEC), Hydroxy propyl cellulose(HPC), Hydroxy propyl
methyl cellulose(HPMC), Sodium carboxy methyl cellulose(NaCMC)
etc
B)-Poly(acrylic acid) polymer-Carbomers, Polycarbophil.
C)-Poly vinyl alcohol(PVC)
Natural Polymers-Chitosan, gum tragacanth, sodium alginate,
xanthan gum, bean gum, gellumgum etc

8. Principle of
Bioadhesion/Mucoadhesion.
An intimate contact between a mucoadhesive and membrane
either from a good wetting of a mucoadhesive and a membrane or
for swelling of bioadhesive/ mucoadhesive.
Penetration of the mucoadhesive into the tissue take place.
Inter penetration of the chains of mucoadhesive with mucous takes
place and then low chemical bond can settle.

9. Several theory have been proposed to
explain the fundamental of mucoadhesion.
1) Wetting theory-Ability of mucoadhesive polymers to spread and
develop immediate attachment with the mucous membrane.
2) Electronic theory-Attractive electrostatic forces between
glycoprotein mucin network and bioadhesivepolymers .
3) Adsorption theory –Surface force( Covalent bond, Ionic bond
and Wander walls force) resulting in a chemical bond.
4) Diffusion theory-Physical entanglement of mucin strands and
flexible polymers chain.
5)Fracture theory-Analyses the maximum tensile stress developed
during detachment of mucoadhesive drug delivery system from the
mucosal surface.

10. Advantage of mucoadhesive drug
delivery system
This system the allow the developing of contacting between
dosage forms and the mucosa.
High drug concentration can be maintained at the absorptive
surface for a prolong period.
Dosage form can be immbolizedspecifically at any part of oral
mucosa, buccal mucosa, sublingual and gingival mucosa etc.

11. Disadvantage of mucoadhesive
drug delivery system.
Small mucosal surface for the contact.
Lack of flexibility of dosage forms.
Difficult to achieve the high drug release rates for some drugs.
Extent and frequency of attachment may cause local irritations.

12. Transmucosal permeability
There are two route are involved in drug permeation across
epithelial membranes the transcellular route and the paracellular
route.
In the studies of mechanism of trans-membrane permeation the
epithelial membrane structure is simplified consists of a lipoidal
pathwayand an aqueous pore pathway.
Skin and git mucosa are considered lipoidal barriers, in which drug
absorption is determined by the magnitude of its partition
coefficient molecular size till the diffusion through aqueous diffusion
layer becomes a rate limiting step in trans membrane permeation.
It has been suggested that the nasal mucosa serves as a modified
lipoidal barrier or lipophilic permeants.

13. The pH partition theory is not applicable for many hydrophilic drugs.
It has also been reported that the logarithm of nasal absorption and
the logarithm of drug molecular weight are linearly correlated for
many water soluble compounds.
This indicates the presence of aqueous pore channel in the nasal
mucosa for the absorption of hydrophilic drugs.
Transmucosal permeation of polar molecules occurs through the
paracellular route .

16. The following barrier exit through
during the paracellular route
The barrier function of basal lamina depend on the molecular
weight of the permeant molecule, it reactivity with the barrier and
the structural and functional factors of the barrier.
Membrane coating granules extrude into the intercellular region of
keratinised and non-keratinised oral epithelium and prevent the
transmucosal penetration of water soluble peptide or protein
The barrier function of keratin layer in oral mucosa is not as well
defined as in the skin.
The permeation rate of water was shown to be greater in non-
keratinisedthan in keratinised oral epithelium but the permeation of
horseradish peroxidase was found to be similar in both mucosae.
The permeability coefficient of solute across the rabbit lingual
frenulum and attached gingiva were determined in vitro conditions.

17. Formulation consideration of buccal
drug delivery system
Drug-Before mucoadhesive drug delivery system are formulated, it
should decided that whether the intended action is action is for rapid
release, prolonged release, local effect and systemic effect.
A suitable drug should be selected based on its pharmacokinetics
properties for designing buccoadhesivedrug delivery system.
The drug should have the following characteristics:
i)The conventional single dose of the drug should be small.
ii)The drug with biological half-life of 2-8 hr are good candidates for
controlled drug delivery.
iii)The drug t-max shows wider fluctuation or higher values on
administration.
iv)The drug may undergo first pass effect or pre-systemic drug
elimination on oral administration.
v)The drug undergoes passive absorption on oral administration.

18. Bioadhesivepolymers
Selection and characterisation of appropriate bioadhesive
polymers is the first step in the development of buccoadhesive
dosage forms.
These polymers are important in buccoadhesivesystem of drug
delivery.
Polymers are also used in matrix device in which drug is embedded
in polymer matrix which control thesduration of drug release.
The drug released in mucous membrane via rate controlling layer or
core layer.
Bioadhesivepolymer adhered to the mucin/epithelial surface are
effective improve the oral drug delivery.

19. Ideal characteristics of bioadhesive
polymers
It should be inert and compatible with the environment.
It should be non-toxic and absorbable from the mucous layer.
It should allow easy incorporation of drug in the formulation.
It should be quickly adhere to moist tissue surface and should
posses site specificity.
It should not decompose on storage or during the shelf life of the
dosage form.
It should be economical and easily available in the market.

20. Backing membranes
It play important role in the attachment of bioadhesivesdevices to
the mucous membrane.
Inert material should be used as backing membrane.
These materials should also be impermeable to the drug and
penetration enhancer.
The resultant impermeable membrane on buccoadhesivepatches
prevent drug loss and improve patient compliance.
Eg-Carbopol, magnesium stearate, HPMC, HPC, CMC etc

21. Plasticisers
These are used for achieving softness and flexibility of thin films
polymers.
They also acts as a permeation enhancers.
Example-Glycerol, PEG 200, PEG400, castor oils

22. Permeation enhancers
These substances facilitate permeation throughout buccal
mucosae.
A suitable permeation enhancers is selected based on the
physiological properties of the drug, administration site , nature of
the vehicle and other excipients.
Eg-Benzalkonium chloride, Cyclodextrin, lauric acid, Sodium
glycocholate etc