•Dr.

Zeenat Iqbal ABDUL MUHEEM

•Dr.sushama Talegaonkar M.PHARM (PHARMACEUTICS)
•Dr.Yasmin Sultana JAMIA HAMDARD
FACULTY OF PHARMACY
JAMIA HAMDARD
NEW DELHI

2/24/2013 Seminar 1
 What is 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.

2/24/2013 Seminar 2
  INTRODUCTION
 Since the early 1980,the concept of Mucoadhesion has
gained considerable interest in pharmaceutical
technology.
 The strategies studied to overcome such obstacles
include the employment of the materials
that,possibly, combine mucoadhesive , 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.
2/24/2013 Seminar 3
 Why are we using Mucoadhesive drug delivery
system(MDDS)?
 MDDS prolng the residence time of the dosage form
at the site of application or absorption.
 Intimate contact of the dosage form with the
underlying absorption .
 Improve the therapeutic performance of drug.
 Should not cause cause irritation.
 High drug loading capacity.
 Controlled drug release(preferably unidirectional
release).

2/24/2013 Seminar 4
 Types of Drug delivery systems:
Depending upon the route of administration of the mucoadhesive drugs
they are different types .They are

1)Buccal delivery system

2)Sub lingual delivery system

3)Vaginal delivery system

4)Rectal delivery system

5)Nasal delivery system

6)Ocular delivery system

7)Gastro intestinal delivery system

 ADVANTAGES-
 MDDS offer several advantages over other controlled oral
controlled release systems by virtue of prolongation of
residence of drug in GIT.
 Targeting & localization of the dosage form at a specific
site.
 High drug flux at the absorbing tissue.
 MDDS will serve both the purposes of sustain release &
presense of dosage form at the site of absorption.
 Excellent accessibility.
 Painless administration.
 Low enzymatic activity & avoid of first pass metabolism.

2/24/2013 Seminar 6
 DISADVANNTAGES-
 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.
 Medications administered orally do not enter the blood
stream immediately after passage through the buccal
mucosa.

2/24/2013 Seminar 7
 Oral cavity: anatomic and physiologic features
 The oral mucosa presents a surface area of about 100
cm2.
 Three different types of oral mucosa-
1-Masticatory mucosa-25% of the total oral mucosa &
covers the gingiva and the hard palate.
2-Lining mucosa- (60% of the total oral mucosa) &
covers the lips, cheeks, soft palate, lower surface of the
tongue and the floor of the oral cavity.
3-The specialized mucosa-(15% of the total oral
mucosa) is found on the dorsum of the tongue

2/24/2013 Seminar 8
 Buccal epithelium-
 The buccal epithelium is non-keratinized and composed of
multiple layers of cells which show different patterns of
maturation between the deepest cells and the surface.
 An intracellular lipid portion is packaged in small
organelles called membrane coating granules or lamellar
granules.
 Granules migrate to the apical surface of the cell where
their membrane fuse with the cell membrane,&lipid
content is extruded in the extracellular space.
 The buccal epithelium is lacking in tight
junctions, common to intestinal and nasal mucosae, and it
is endowed with gap junctions, desmosomes and
hemidesmosomes , which are loose intercellular links.
2/24/2013 Seminar 9
 Structure of the mucosa of the oral cavity: 1) mucus layer;
2) epithelium; 3) connective tissue (lamina propria); 4)
smooth muscle layer

2/24/2013 Seminar 10
COMPOSITION OF MUCUS
LAYER:
‘Mucus is translucent and viscid secretion which
forms a thin continuous gel adherent to mucosal
epithelial surface.’
 Water - 95%
 Glycoprotein and lipids - 0.5-5%
 Mineral salts - 1%
 Free proteins - 0.5-1%
MUCOADHESION THEORY
Electronic theory
 Electronic theory is based on the premise that both
mucoadhesive and biological materials possess
opposing electrical charges. Thus, when both
materials come into contact, they transfer electrons
leading to the building of a double electronic layer at
the interface, where the within this electronic double
layer determines the mucoadhesive strength.
 Drug transport mechanism
 Two major routes-(1) Transcellular (Intracellular)
(2) Paracellular (intercellular)
 The transcellular route involves the crossing of the cellular
membranes with a polar and a lipid domain.
 The paracellular essentially implicates the passive diffusion
through the extracellular lipid domain.
 To reach the systemic circulation ,drugs must also
overcome an enzymatic barrier represented by the enzymes
that are present on the mucosal surface & mucosa.
 Aminopeptidase,carboxypeptidase & estrase were found in
homogenates of human epithelial cell culture.

2/24/2013 Seminar 13
 Mechanism of Mucoadhesion-
 Generally divided into two steps-(a)contact stage
(b)consolidation stage
 first is characterized by the contact b/w the
mucoadhesive &the mucus membrane ,with
spreading & swelling of the formulation, initiating
its deep contact with mucus layer.
 In step (b)the mucoadhesive material are
activated by the presence of moisture

2/24/2013 Seminar 14
2/24/2013 Seminar 15
 Formulation design-
 In case of both mucosal(local) & transmucosal
(systemic) adm., conventional dosage are not able to
assure therapeutic level.
 In MDDS contain the following functional agents-
(1) Mucoadhesive agents
(2) Penetration enhencers
(3) Enzyme inhibitors
 Mucoadhesive agents-the polymer hydration &
consequently the mucus cohesive properties that
promote mucoadhesion .
 Swelling should favour polymer chain flexibility &
interpenetration b/w polymer & mucin chains.

2/24/2013 Seminar 16
  Ex-Polyacrylic acid (PAA)
Polyvinyl alcholal(PVA)
Sodium carboxymethylcelluose(NaCMC)
Sodium alginate
HPMC
HEC
HPC
 Various copolymer of acrylic acid suchas acrylic acid –
polyethylene glycol monomethyl ether copolymer have also
been studied.
Penetration enhancers(PE)-
 PE are also required when a drug has to reach the systemic
circulation to exert its action .
 Must be non-irritant &have a reversible effect.

2/24/2013 Seminar 17
  Recently chitosan & its derivatives, polymers
already known for MA properties.chitosan help
transportion of drug throw paracellular pathway.
List of Permeation Enhancer :-
 Benzalkonium chloride
 Dextran sulfate
 Fatty acid
 Propyleneglycol
 Menthol
 Phosphatidylcholine
 Polysorbate 80
 Sodium EDTA
2/24/2013 Seminar 18
 Enzyme inhibitors-
 Drug +enzyme inhibitors---->improving the
buccal absorption of drugs,particulary peptides.
Ex-1-Aprotinin
2-Bestatin
3-Puromycin
bile salts stabilise 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)
2/24/2013 Seminar 19
 FACTORS AFFECTING MUCOADHESION-
1-Mol. Wt.-Mucoadhesive is increase with mol wt above
100,000.
2-Flexibility-Mucoadhesive starts with the diffusion of the
polymer chains in the interfacial region.
 Polymer chains contain a substantial degree of flexibility in
order to achieve the desried entanglement with mucus.
3-cross linked density-increse the density of cross
linkedinsufficient of swellingdecrease rate of
interpenetration b/w polymer & mucin.
4-hydrogen bonding capacity-desired polymer must have
functional grps that are able to form hydrogen bonds &
flexibility of the polymer is improve this hydrogen bonding
potential.

2/24/2013 Seminar 21
 4-Hydration-polymer swelling permits a mechanical
entanglement by exposing the bioadhesive sites for
hyrogen bonding/ electrostatic interaction b/w
polymer &mucus network.eg-HMA,PVA.
5-Concentration-when conc.of the polymer is low ,the
number of penetrating polymer chains per unit
volume of mucus is small & interaction b/w polymer
&mucus is unstable.
 In general the more concentrated polymer would
result in longer penetrating chain length & better
adhesion.

2/24/2013 Seminar 22
  Higher conc.of polymer do not necessarily improve &
,in some cases, actually diminshed mucoadhesive
properties.
eg-high conc.of the flexible polymeric films based on
polyvinyl pyrrolidone as film forming polymer did not
further enhance the muco adhesive properties of the
polymer.

2/24/2013 Seminar 23
 Dosage form-
 most common formulation in MDDS are tablets &
patches.various dosage which are given in below-
(1)Matrix tablets
(2)Patches
(3)Films
(4)Gels &ointments
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.

2/24/2013 Seminar 24
2/24/2013 Seminar 25
 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.

Patches-
 Greater patient complaince compared with
tablets owing to their physical flexibility that
causes only minor discomfort to the patient.
 Ex-tyrotropin–releasinghormone(TRH)
oxytocin,calcitonin etc.
2/24/2013 Seminar 26
 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.

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.
 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.
2/24/2013 Seminar 27
 Dosage structures Release Effect Active
form ingredient

Matrix Monolithic Sustained/ Local/ Local-

tablets matrix bidire. systemic metronidazo
le;systemic-
propanolol,
timolol

Two-layer Bi direct. Local As above

matrix mention

Two-layer Monodirect. Local/system As above

matrix ic
coated with
impermeable
layer

2/24/2013 Seminar 28
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
 CASE STUDY IN EUDRAGIT BASED MUCOADHESIVE
BUCCAL PATCHES OF SALBUTAMOL SULFATE
 Salbutamol(B2 adrenergic receptor agonist) is used for
relief of bronchospasm in case of asthma & COPD.
 oral bioavailability is 40%(due to 1st pass effect) ,so
salbutamol patches were prepared using Eudragit L-
100,HPMC,PVA,& Carbopol934 in various proportions with
PEG-400/PG as plasticizers.
 SS is usually is adm. via inhaled route for direct effect on
bronchial smooth muscle,but also have some
disadvantages like inaccuracy of dosing,patient complaince
due to CFC,cost of the prepration &frequency of
administration

2/24/2013 Seminar 30
  SS Patches were prepared by solvent casting techniques.
 In which eudragit in ethanol,HPMC in ethanol:acetone
mixture (3:1) & PVA in water
 5ml of eudragit ,5ml of ethanol & 0.05% of tween 80 mixed
well on magnetic stirrer at low rpm.
 In above mixture added 2ml of PG or PEG was added &
mixed low rpm,drug soln must be bubble free.
 The soln was poured in teflon coated circular dish &hen
dried in room temp.for 2hrs & further dried for 18hrs at
4O0C in hot air oven.
 The patches were laminated on one side with water
permeable backing layer.

2/24/2013 Seminar 31
EVALUATION TESTS OF PATCHES
1. Mass uniformity & thickness
2. Drug content
3. Swelling index
4. Measurment of surface PH
5. Residence time
6. Bioadhesion test: By tensile strength, shear strength,
Fluorescent probe method, Atomic force microscopy
(AFM), falling liquid film method,
7. Permeability study: Using different diffusion cells
8. Release rate study: Using USP dissolution test using
rotating paddle dissolution test apparatus.
 CONCLUSION-
 The mucoadhesive drug delivery offers several advantages
for controlled drug delivery. The mucosa is well supplied
with both vascular and lymphatic drainage.
 Mucoadhesive drug delivery is a promising area for
systemic delivery of orally inefficient drugs as well as an
attractive alternative for noninvasive delivery of potent
peptide and perhaps protein drug molecules.
 A rational approach to dosage form design requires a
complete understanding of the physicochemical and
biopharmaceutical properties of the drug and excipients.

2/24/2013 Seminar 33