NDDS TOPICS BY PROF. SHASHANK CHAURASIYA

1. Prepared By:
Prof. SHASHANK CHAURASIYA
Bansal College of Pharmacy, Bhopal
Mucoadhesive drug delivery system
1

2. •
•
•
•
•
•
•
•
•
•
2
Introduction
Basics ,concepts & mucosal membrane.
Need of mucoadhesive DDS
Mechanism of mucoadhesion
Theories mucoadhesion Sites of
mucoadhesion Penetration enhancer
Mucoadhesive polymer
Factor affecting mucoadhesion
Advantages & Disadvantages
Mucoadhesive dosage form Evaluation

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 effects.
• 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 ?
6
• 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%
•
•
•
•
•
•
•

7. General structure of mucous layer
7

8. Functions of mucus
8
• 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.

9. Avoidance
of
First pass
Metabo
lism
Better absorption
of peptide by
penetration
enhancer
Prolong
residence time
Localization
of drug at
given site
WHY ?
9

10. Mechanisms of mucoadhesion
10
• 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)
•
•
•

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 affinity 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
• Diffusion theory
• Fracture theory
14

15. 1) Electronic theory
-Attractive electrostatic forcesbetween
mucin network & the bioadhesive material.
15
glycoprotein
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

16. 4) Diffusion theory
-Physical entanglement of mucinstrands
and flexible polymer chains.
5) Fracture theory
-Analyses the maximum tensile stress develop during
detachment of the BDDS from mucosal surfaces
16

17. Different routes of targeting
MDDS
17

18. Penetration enhancer
• Substances that facilitate the permeation through
referred as permeation enhancers .
mucosa are
• 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 ,
,Sodium EDTA etc.
•
Propyleneglycol, Men
18

19. Mucoadhesuve polymers
19
• 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 strongnon-covalent bond with
mucin epithelial cell surface
•
•
•
•
•
•

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
Aminodextran, Chitosan, Carbopol,
SodiumAlginate, Pectin, SodiumCMC, etc.
Uncharged
Starch, PEG, PVA, PVP, etc.
21

22. Factors affecting 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 state•22

23. Advantages
-Advantages over other controlled oral controlled
release systems by 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
virtue of
-If MDDS are adhere too tightlgy because it is undesirable to exert too much force
to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often 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&soft,
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.
Certainpolymer 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
28
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.

29. .
THANK YOU…