MUCOADHESIIVE DRUG DELIVERY SYSTEM

Mucoadesive Drug Delivery
System
Dr. Gajanan S. Sanap M.Pharm.,Ph.D
Department of Pharmaceutics
Ideal College of Pharmacy and Research
Kalyan 421- 306

 Bioadhesion can be defined as the state in which two materials, at least one of
which is biological in nature, are maintained together for a prolonged time period
by means of interfacial forces
 During the 1980s, this concept began to be applied to drug delivery systems.
It consists of the incorporation of adhesive molecules into some kind of
pharmaceutical formulation intended to stay in close contact with the absorption
tissue, releasing the drug near to the action site, thereby increasing its
bioavailability and promoting local or systemic effects
INTRODUCTION
2
Purpose of drug delivery :- (a) Local
(b) Systemic

Type 1, adhesion between two biological phases, for example, platelet aggregation
and wound healing.
Type 2, adhesion of a biological phase to an artificial substrate, for example, cell
adhesion to culture dishes and biofilm formation on prosthetic devices and inserts.
Type 3, adhesion of an artificial material to a biological substrate, for example,
adhesion of synthetic hydrogels to soft tissues and adhesion of sealants to dental
enamel.
CLASSIFICATION OF BIOADHESION
3
For drug delivery purposes, the term bioadhesion implies attachment of a drug
carrier system to a specified biological location.
The biological surface can be epithelial tissue or the mucus coat on the surface of
a tissue.
If adhesive attachment is to a mucus coat, the phenomenon is referred to as
mucoadhesion

1. A prolonged residence time at the site of drug action or absorption.
2. A localization of drug at a given target site.
3. An increase in the drug concentration gradient due to the intense contact of
particles with the mucosa
4. A direct contact with intestinal cells that is the first step before particle
absorption
5. Ease of administration
6. Termination of therapy is easy.{except gastrointestinal}
7. Permits localization of drug to the oral cavity for a prolonged period of time
8. Can be administered to unconscious patients. {except gastrointestinal}
9. Offers an excellent route, for the systemic delivery of drugs with high first pass
metabolism, thereby offering a greater bioavailability
10. A significant reduction in dose can be achieved there by reducing dose related
side effects
ADVANTAGES
4

11. Drugs which are unstable in the acidic environment or destroyed by enzymatic
or alkaline environment of intestine can be administered by this route. Eg.
Buccal sublingual, vaginal
12. Drugs which show poor bioavailability via the oral route can be administered
conveniently
13. It offers a passive system of drug absorption and does not require any
activation
14. The presence of saliva ensures relatively large amount of water for drug
dissolution unlike in case of rectal and transdermal routes {buccal mucosa}
15. Systemic absorption is rapid
16. This route provides an alternative for the administration of various hormones,
narcotic analgesic, steroids, enzymes, cardiovascular agents etc
17. The buccal mucosa is highly perfused with blood vessels and offers a greater
permeability than the skin
18. Less dosing frequency
19. Shorter treatment period
20. Increased safety margin of high potency drugs due to better control of plasma
levels
5

21. Maximum utilization of drug enabling reduction in total amount of drug
administered
22. Improved patient convenience and compliance due to less frequent drug
administration
23. Reduction in fluctuation in steady state levels and therefore better control
of disease condition and reduced intensity of local or systemic side effects
6

7
1. Drugs, which irritate the oral mucosa, have a bitter or unpleasant taste,
odour, cannot be administered by this route
2. Drugs, which are unstable at target site pH cannot be administered by this
route
3. Only drugs with small dose requirements can be administered {except GI}
4. Only those drugs, which are absorbed by passive diffusion, can be
administered by this route
5. Eating and drinking may become restricted {buccal mucosa}
6. Swallowing of the formulation by the patient may be possible {buccal
mucosa}
7. Over hydration may lead to the formation of slippery surface and structural
integrity of the formulation may get disrupted by the swelling and hydration
of the bioadhesive polymers
LIMITATIONS

8
AVOIDANCE
OF FIRST PASS
METABOLISM
WHY ?
INCREASE IN
DRUG CONC.
GRADIENT
BETTER
ABSORPTION
OF PEPTIDE BY
PENETRATION
ENHANCER
LOCALIZATION
OF DRUG AT
GIVEN SITE
PROLONG
RESIDENCE
TIME
NEED OF MUCOADHESIVE DDS

Mucous membranes are the moist linings of the orifices and internal parts of the
body
They cover, protect, and provide secretory and absorptive functions
Mucosal membranes are relatively permeable and allow fast drug absorption.
They are characterized by an epithelial layer whose surface is covered by mucus.
MUCOUS MEMBRANE
9
Mucus is a translucent and visco-elastic secretion, which forms a thin,
continuous gel blanket adherent to mucosal epithelial surface.
The mean thickness of this layer varies from about 50-450 μm in humans.
MUCUS

It is secreted by the goblet cells
lining the epithelia
10
or by special exocrine glands
with mucus cells acini.

The primary constituent of mucus is a glycoprotein known as mucin as well
as water and inorganic salts.
These units contain an average of about 8-10 monosaccharide residues of five
different types.
They are:
a) L-fructose
b) D-galactose
c) N-acetyl-D-glucosamine
d) N-acetyl-D-galactosamine
e) Sialic acid
COMPOSITION OF MUCUS
11

Complex-high molecular weight macromolecule consisting of a polypeptide
(protein) backbone to which carbohydrate side chains are attached
Generic structure of mucin monomer
Mucus forms flexible, threadlike strands that are internally cross linked by
disulphide bond
STRUCTURE OF MUCUS
12

Protective role: The Protective role results particularly from its hydrophobicity
and protecting the mucosa from the lumen diffusion of hydrochloric acid from the
lumen to the epithelial surface
Barrier role: The mucus constitutes diffusion barrier for molecules, and
especially against drug absorption diffusion through mucus layer depends on
molecule charge, hydration radius, ability to form hydrogen bonds and molecular
weight.
Lubrication role: An important role of the mucus layer is to keep the membrane
moist. Continuous secretion of mucus from the goblet cells is necessary to
compensate for the removal of the mucus layer due to digestion, bacterial
degradation and solubilisation of mucin molecules.
Adhesion role: Mucus has strong cohesive properties and firmly binds the
epithelial cells surface as a continuous gel layer
Mucoadhesion role: At physiological pH, the mucus network may carry a
significant negative charge because of the presence of sialic acid and sulphate
residues and this high charge density due to negative charge contributes
significantly to the bioadhesion
FUNCTIONS OF MUCUS LAYER
13

Stage 1: Contact stage
 Stage 2: Consolidation stage
STAGES OF MUCOADHESION
15

It is a three step process:-
STEP 1: Wetting and swelling of polymer
STEP 2: Interpenetration between the polymer chains and the mucosal
membrane.
STEP 3: Formation of Chemical bonds between the entangled chains.
MECHANISM OF MUCOADHESION
16

The wetting and swelling step occurs when the
polymer spreads over the surface of the
mucosal membrane in order to develop an
intimate contact with the substrate.
This can be readily achieved by placing a
bioadhesive formulation such as a tablet or
paste within the oral cavity or vagina.

Bioadhesives are able to adhere to or bond with
biological tissues by the help of the surface
tension and forces that exist at the site of
adsorption or contact.
Swelling of polymers occur because the
components within the polymers have an
affinity for water.
STEP 1
17

The surface of mucosal membranes are
composed of high molecular weight polymers
known as glycoproteins.
In this step interdiffusion and interpenetration
take place between the chains of mucoadhesive
polymers and the mucous gel network creating
a great area of contact.
The strength of these bond depends on the
degree of penetration between the two polymer
groups.
In order to form strong adhesive bonds, one
polymer group must be soluble in the other and
both polymer types must be of similar chemical
structure.
STEP 2
18

In this step entanglement and formation of weak chemical bonds as well as
secondary bonds between the polymer chains and mucin molecules occur
The types of bonding formed between the chains include primary bonds such
as covalent bonds and weaker secondary interactions such as van der Waals
Interactions and hydrogen bonds.
Both primary and secondary bonds are exploited in the manufacture of
bioadhesive formulations
STEP 3
19

1. Electronic theory
2. Adsorption theory
3. Wetting theory
4. Diffusion theory
5. Fracture theory
6. Mechanical theory
THEORIES
OF
MUCOADHESION

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 attractive
forces within this electronic double layer determines the mucoadhesive strength
ELECTRONIC THEORY
21
ADSORPTION THEORY
It is a surface force where surface molecules of adhesive and adherent are in
contact. According to adsorption theory, bioadhesive systems adhere to tissue due
to bond formation.
* Primary Chemical Bonds
Many bioadhesives can form primary chemical covalent bonds with functional
chemical groups in mucin:
Aldehydes and alkylating agents can readily react with amino groups and
sulfhydryl groups.
Acylating agents react with amino and hydroxyl groups of serine or tyrosine.

* Secondary chemical bonds:
Hydrogen bonding, electrostatic forces or Van-der Waals attractions are sufficient to
contribute adhesive joints.
The wetting theory applies to liquid systems which present affinity to the
surface in order to spread over it. This affinity can be found by using measuring
techniques such as the contact angle. The general rule states that the lower the
contact angle then the greater the affinity
The contact angle should be equal or close to zero to provide adequate
spreadability
The spreadability coefficient, SAB, can be calculated from the difference between
the surface energies γB and γA and the interfacial energy γAB, as indicated in
equation (1)
WETTING THEORY

The greater the individual surface energy of mucus and device in relation to the
interfacial energy, the greater the adhesion work, WA, i.e. the greater the energy
needed to separate the two phases
23

Diffusion theory describes the interpenetration of both polymer and mucin
chains to a sufficient depth to create a semi-permanent adhesive bond
It is believed that the adhesion force increases with the degree of penetration of
the polymer chains
This penetration rate depends on the diffusion coefficient, flexibility and nature
of the mucoadhesive chains, mobility and contact time
According to the literature, the depth of interpenetration required to produce an
efficient bioadhesive bond lies in the range 0.2-0.5 μm. This interpenetration
depth of polymer and mucin chains can be estimated by equation 3:
DIFFUSION THEORY
where t is the contact time, and
Db is the diffusion coefficient of the
mucoadhesive material in the mucus
24

The adhesion strength for a polymer is reached when the depth of penetration is
approximately equivalent to the polymer chain size
In order for diffusion to occur, it is important that the components involved have
good mutual solubility, that is, both the bioadhesive and the mucus have similar
chemical structures
The greater the structural similarity, the better the mucoadhesive bond
25
FRACTURE THEORY
•This is perhaps the most used theory in studies on the mechanical measurement
of mucoadhesion.
•It analyzes the force required to separate two surfaces after adhesion is
established.

This force, sm, is frequently calculated in tests of resistance to rupture by the ratio
of the maximal detachment force, F m, and the total surface area, A0 , involved in
the adhesive interaction
26
the fracture force, sf, which is equivalent to the maximal rupture tensile
strength, sm, is proportional to the fracture energy (gc), for Young’s module (E)
and to the critical breaking length (c) for the fracture site, as described in
equation

Since the fracture theory is concerned only with the force required to separate the
parts, it does not take into account the interpenetration or diffusion of polymer
chains.
Consequently, it is appropriate for use in the calculations for rigid or semi-rigid
bioadhesive materials, in which the polymer chains do not penetrate into the
mucus layer
27
Mechanical theory considers adhesion to be due to the filling of the irregularities
on a rough surface by a mucoadhesive liquid.
Moreover, such roughness increases the interfacial area available to interactions
thereby aiding dissipating energy and can be considered the most important
phenomenon of the process
MECHANICAL THEORY


Polymer

Environment
 Physiology
28
FACTORS AFFECTING MUCOADHESION

i. Molecular weight
ii.Concentration of active polymer
iii.Flexibility of polymer chains
iv.Spatial confirmation
v.Cross linking density
vi.Charge
vii.Hydration
29
POLYMERRELATEDFACTORS

The interpenetration of polymer molecules is favorable for low molecular weight
polymer
Entanglement of polymer chains is favoured for high molecular weight polymer
The mucoadhesive strength of a polymer increases with molecular weights above
1,00,000.
Direct correlation between the mucoadhesive strength of polyoxyethylene
polymers and their molecular weights lies in the range of 2,00,000-70,00,000.
1. MOLECULAR WEIGHT
30

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.
Therefore, higher concentrations of polymers do not necessarily improve and, in
some cases, actually diminish mucoadhesive properties.
2. CONCENTRATION OF ACTIVE POLYMER
31

One of the studies addressing this factor demonstrated that high concentrations of
flexible polymeric films based on polyvinylpyrrolidone or poly(vinyl alcohol) as
film-forming polymers did not further enhance the mucoadhesive properties of the
polymer
32
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.
In general, mobility and flexibility of polymers can be related to their viscosities
and diffusion coefficients, as higher flexibility of a polymer causes greater
diffusion into the mucus network
3. FLEXIBILITY
32

Besides molecular weight or chain length, spatial conformation of a molecule is
also important
Despite high molecular weight of dextran (19,500,000), they have adhesive
properties same as PEG having molecular weight 2,00,000
The helical conformation of dextrans shields the adhesive groups
PEG polymers have a linear structure.
33
4. SPATIAL CONFORMATION

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
34
4. CROSS LINKING DENSITY
5. CHARGE
•Strong anionic charge on the polymer is one of the required characteristics for
mucoadhesion
•Nonionic polymers appear to undergo a smaller degree of adhesion compared
to anionic polymers.

 Some cationic polymers demonstrate superior mucoadhesive properties,
especially in a neutral or slightly alkaline medium. Additionally, some cationic
high-molecular-weight polymers, such as chitosan, have shown to possess good
adhesive properties.
There is no significant literature about the influence of the charge of the
membrane on the mucoadhesion but the pH of the membrane affects the
mucoadhesion as it can influence the ionized or un-ionized forms of the
polymers.
35
6. HYDRATION
•Hydration is required for a mucoadhesive polymer to expand and create a proper
macromolecular mesh 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

i.pH of polymer - substrate interface
ii.Applied strength
iii.Initial contact time
iv.Swelling
36
ENVIRONMENTRELATED
FACTORS

 The pH at the bioadhesive to substrate interface can influence the adhesion of
bioadhesives possessing ionizable groups.
 Many bioadhesives used in drug delivery are polyanions possessing carboxylic acid
functionalities.
 If the local pH is above the pKa of the polymer, it will be largely ionized; if the pH is
below the pKa of the polymer, it will be largely unionized.
 The approximate pKa for the poly(acrylic acid) family of polymers is between 4 and 5.
 The maximum adhesive strength of these polymers is observed around pH 4-5 and
decreases gradually above a pH of 6.
 A systematic investigation of the mechanisms of mucoadhesion clearly showed that the
protonated carboxyl groups, rather than the ionized carboxyl groups, react with mucin
molecules, presumably by the simultaneous formation of numerous hydrogen bonds
37
1. pH OF POLYMER - SUBSTRATE INTERFACE

Higher forces lead to enhanced interpenetration and high bioadhesive strength.
38
2. APPLIED STRENGTH
2. INITIAL CONTACT TIME
The greater the initial contact time between bioadhesive and substrate, the
greater the swelling and interpenetration of polymer chains

It depends on both polymer and environment
Interpenetration of chains is easier as polymer chains are disentangled and free of
interactions
When swelling is too great, a decrease in bioadhesion occurs.
Such a phenomena must not occur too early in order to lead to sufficient
bioadhesion
Swelling later allows easy detachment of the bioadhesive system after complete
release of drug
39
4. SWELLING

i. Mucin turnover rate
ii. Disease states
40
PHYSIOLOGICALFACTORS

It is important because:
 It limits the residence time of the mucoadhesive on the mucus layer
 Mucin turnover results in substantial amounts of free mucin molecules
which interact with the mucoadhesive before it can reach the mucus layer.
Mucin turnover depends on presence of food
Mucociliary clearance in the nasal cavity – 5 mm/min
Mucociliary clearance in the tracheal region – 4-10 mm/min
41
MUCIN TURNOVER RATE

Physicochemical properties of mucus is known to change in conditions like:
 Common cold
 Gastric ulcers
 Ulcerative colitis
 Cystic fibrosis
 Bacterial and fungal infections of the female reproductive system
 Inflammation of the eye
42
DISEASE STATES

Polymers which adhere to mucin-epithelial surface are broadly classified as:
1.Polymers that become sticky when placed in water and owe their
mucoadhesion to stickiness
2.Polymers that adhere through non-specific, non-covalent interactions
3.Polymers that bind to specific receptor sites on the cell surface
43
MUCOADHESIVE POLYMERS

Ideal characteristics of mucoadhesive polymer are as follows:
1.The polymer and its degradation product should be non-toxic and non-absorbable
from GIT
2.Non-irritant to mucous membrane
3.Should preferably form strong non-covalent bond with mucin
4.Should adhere quickly to moist tissue
5.Site specific
6.Should allow easy incorporation of drug
7.Should not offer any hindrance to drug release
8.Must not decompose on storage throughout the shelf life of the formulation
9.Should have an optimum degree of cross-linking density, pH and hydration
10.Should be economic
44

These materials are natural or synthetic hydrophilic molecules containing
numerous organic functions that generate hydrogen bonds such as carboxyl,
hydroxyl and amino groups, which do not adhere specifically.
These polymers can be subdivided into three classes: cationic, anionic and
nonionic.
Cationic molecules can interact with the mucus surface, since it is negatively
charged at physiological pH. Eg. Chitosan
Mucoadhesion of chitosan occurs because of the electrostatic interactions of
their amino groups with the sialic groups of mucin in the mucus layer.
46
FIRST GENERATION POLYMERS

In contrast, synthetic polymers derived from polyacrylic acid (carbomers) are
negatively charged but are also mucoadhesive. In this case, mucoadhesion
results from physical-chemical processes, such as hydrophobic interactions,
hydrogen and van der Waals bonds, which are controlled by pH and ionic
composition.
Other examples of anionic polymers are carboxymethylcellulose and alginates
Nonionic polymers, including hydroxypropylmethylcellulose,
hydroxyethylcellulose and methylcellulose, present weaker mucoadhesion
force compared to anionic polymers
There is a new class of substances being identified as bioadhesive. This class
consists of ester groups of fatty acids, such as glyceryl monooleate and
glyceryl monolinoleate
47

48
POLYMER BIOADHESIVE
PROPERTY
Carboxy methyl cellulose +++
Carbopol 934 +++
Polycarbophil +++
Tragacanth +++
Poly (acrylic acid / divenyl benzene) +++
Sodium alginate +++
Hydroxy ethyl cellulose +++
Gum karaya ++
Gelatin ++
Guar gum ++
+++ :- Excellent ++ :- Fair

49
POLYMER BIOADHESIVE
PROPERTY
Thermally modified starch +
Pectin +
PVP +
Acacia +
PEG +
Psyllium +
Amberlite – 200 resin +
HPC +
Chitosan +
Hydroxy ethyl methacrylate +
+ :- Poor

An ideal polymer should exhibit the ability to incorporate both hydrophilic
and lipophilic drugs, show mucoadhesive properties in its solid and liquid
forms, inhibit local enzymes or promote absorption, be specific for a
particular cellular area or site, stimulate endocytosis and finally to have a
broad safety range
These novel multifunctional mucoadhesive systems are classified as second
generation polymers
They are an alternative to non-specific bioadhesives because they bind or
adhere to specific chemical structures on the cell or mucus surface.
Good examples of these molecules are lectins, invasins, fimbrial proteins,
antibodies, and those obtained by the addition of thiol groups to known
molecules.
51
SECOND GENERATION POLYMERS

Permeation enhancers are substances added to pharmaceutical formulation in
order to increases the membrane permeation rate or absorption rate of a co-
administered drug.
They are used to improve bioavailability of drugs with normally poor
membrane permeation properties without damaging the membrane and
causing toxicity.
Enhancer efficacy depends on the physiochemical properties of the drug,
administration site, nature of the vehicle and whether enhancer is used alone
or in combination
52
PERMEATION ENHANCERS

Categories and examples of membrane permeation
enhancers
A.Bile salts and other steroidal detergents:
Sodium glycocholate, Sodium taurocholate, Saponins, Sodium tauro
dihydro fusidate and Sodium glycol dihydrofusidate.
B. Surfactants:
1. Non- ionic: Laureth-a, Polysorbate-9, Sucrose esters and do-decyl
maltoside
2. Cationic: Cetyl trimethylammonium bromide
3. Anionic: sodium lauryl sulfate
C. Fatty acids: oleic acid, lauric acid, caproic acid
D. Other enhancers:
1. Azones
2. Salicylates
3. Chelating agents
4. Sulfoxides e. g. Dimethyl Sulfoxide (DMSO)
53

Solid
Tablets
Bioadhesive microparticles
Bioadhesive inserts
Bioadhesive wafers
Lozenges
Semisolid
Gels
Films
Liquid
Suspensions
Gel forming liquids
BIOADHESIVE
DOSAGE FORMS

POTENTIA
L
SITES………
..
BUCCAL SUBLINGUAL
ORALNASAL OCULAR
VAGINALRECTAL
Routes

57
Oral Bioadhesive Formulations
 Oral bioadhesive formulations are topical products designed to deliver
drugs to the oral cavity which act by adhering to the oral mucosa and
therefore produce localised effects within the mouth
The oral cavityThe oral cavity
Important functions which include
chewing, speaking and tasting. Some of
these functions are impaired by
diseases such as ulcers, microbial
infections and inflammation.

 In contact with saliva Dosage form become adhesive and render system
attached to mucosa
Drug solution rapidly absorbed throug the the reticulated vein which is
underneath the oral mucosa & transported through facial vein ,internal jugular
vein ,Brachiocephalic vein .
Rapid absorption –peak 1to 2 min
Some of the common conditions - Mouth ulcersMouth ulcers , Oral thrush,Oral thrush,
Gingivitis.Gingivitis.

The buccal mucosa refers to the
inner lining of the lips and cheeks.
 The epithelium of the buccal mucosa is about 40-50 cells thick and the
epithelial cells become flatter as they move from the basal layersbasal layers to the
superficial layers.
The buccal mucosa is less preferable compared to other oral drug
delivery systems because of vary short transit time.
The bioadhesive polymers can retention of a dosage form by spreading it
over the absorption site.
A ) The Buccal MucosaA ) The Buccal Mucosa

B ). The sublingual mucosaB ). The sublingual mucosa
The sublingual mucosa surrounds
the sublingual gland which is a
mucin-producing salivary glandsalivary gland
located underneath the tongue.
Examples :- Glyceryl Trinitrate (GTNGlyceryl Trinitrate (GTN) (aerosol spray and tablet in
prophylacticprophylactic treatment of angina.)
Brand name:-Susadrin ,Nitrogard.

3 ) The Gingival Mucosa
Hardest muscle of body
Can retain dosage form
for long duration

EXAMPLES OF PRODUCTSEXAMPLES OF PRODUCTS
. Oral Bioadhesive Formulations
CorlanCorlan®® Corlan pellets are used in the treatment of mouth ulcers to reduce the
pain, swelling and inflammation associated with mouth ulcers.The active ingredient
of the pellet is Hydrocortisone succinate. It also contains the bioadhesive polymer
AcaciaAcacia which helps prolong the effect of the drug in the oral cavity. For treatment to
be successful each pellet or lozenge must be allowed to slowly dissolve in the
mouth, close to the ulcer.

Oral Bioadhesive Formulations
 BonjelaBonjela®® This gel is used in the treatment of the soreness associated with mouth
ulcers.The gel is applied over the ulcer every three to four hours or when needed.
Bonjela® contains hypromellose 4500 which lubricates the ulcers .
 Daktarin®Daktarin® oral gel contains the antifungal agent Miconazole and is used to treat
oral thrush. It also contains an adhesive agent known as pregelatinised potato starchpregelatinised potato starch
which increases the viscosity of the gel and also enables it to stick to the oral
mucosa. Patients are advised apply the gel in the mouth and keep it there for as long
as possible preferably after food so the gel remains intact for longer.
 Corsodyl®Corsodyl® oral gel contains the active ingredient chlorhexidine gluconate and is
brushed on the teeth to inhibit the formation of plaque and therefore improve oral
hygiene.The gel also contains the bioadhesive polymer Hydroxypropyl cellulose(HPC)Hydroxypropyl cellulose(HPC)
which helps retain the gel inside the oral cavity.11111

.The Buccal Mucosa.The Buccal Mucosa Examples of ProductsExamples of Products
 BuccastemBuccastem®® Is a drug used in the treatment of nausea, vomiting and
vertigo. It contains the bioadhesive agents Polyvinylpyrrolidone and
Xanthan gum.
 SuscardSuscard®® Is a buccal tablet used in the treatment of angina. It contains
the bioadhesive agent Hydroxypropyl methylcellulose (HPMC).
The sublingual mucosaThe sublingual mucosa Examples of ProductsExamples of Products
Examples of sublingual products include Glyceryl Trinitrate (GTNGlyceryl Trinitrate (GTN) aerosol spray
and tablet which is administered under the tongue for the prophylacticprophylactic treatment of
angina.
11

RECTAL MUCOSAL DRUG
DELIVERY
The rectum is the terminal or end portion of the
gastrointestinal tract. It is an important route
of administration for drugs that have severe
gastrointestinal side effects. This route is also
suitable for patients who cannot take medicines
via the oral route such as unconscious patients
and infants.
The drugs absorbed from the rectum can escape
breakdown by hepatic enzymes. For this reason
mucoadhesive suppositories have been developed
for the local treatment of diseases such as haemorrhoids
and rectal cancer.

FACTORS AFFECTING RECTAL
ABSORPTION
Formulation (time to liquefaction of suppositories)
Volume of liquid
Concentration of drug
Length of rectal catheter ( site of drug delivery)
Presence of stool in the rectal vault
pH of the rectal contents
Rectal retention of drug(s) administered
Differences in venous drainage within the
rectosigmoid region
Partition coefficient of drug
Physical state of medicament
Presence of adjuncts in base

RECTAL FORMULATIONS
• SUPPOSITORIES
- MUCOADHESIVE SUPPOSITORIES
- MUCOADHESIVE LIQUID SUPPOSITORIES
- THERMO REVERSIBLE SUPPOSITORIES
• BIOADHESIVE GEL
• HYDROGEL
• MICROPARTICULATE
-- MICROCAPSULES
-- NANOSPHERES

POLYMERS
• SUPPOSITORIES
- SODIUM ALGINATE AND POLOXAMER
- PEG AND POLYCARBOPHIL
• GEL
- PLURONIC F-127
• HYDROGEL
• CARBOPHIL
• SODIUM ALGINATE
• MICROPARTICULATE

DRUGS
• SUPPOSITORY — PROPANOLOL, INSULIN
• BIOADHESIVE GEL – INSULIN
• HYDROGEL – PROPRANOLOL
• MICROSPHERE -- INDOMETHACIN

EVALUATION
• FOR SUPPOSITORIES
• SURFACE CHARACTERISTICS
• DRUG DISSOLUTION OR RELEASE
• DISINTEGRATION
• MELTING/ SOFTENING OF SUPPOSITORIES
• MUCOADHESIVE STRENGTH
• FOR GEL AND MICROPARTICULATE SYSTEM --- SAME AS
ABOVE.

Flow through cell apparatusFlow through cell apparatus
1. Cell for suppositories1. Cell for suppositories
2. Cell for ointment2. Cell for ointment
USP 27-NF 22, The United StateUSP 27-NF 22, The United State

Rectal Bioadhesive Formulations
EXAMPLES OF PRODUCTSEXAMPLES OF PRODUCTS
 AnacalAnacal®® Is a rectal ointment used to relieve the symptoms associated with
haemorrhoids. It contains the bioadhesive agent polyethylene high polymer 1500.polyethylene high polymer 1500.
 Germoloids®Germoloids® Is a rectal ointment used to relief the pain, swelling, itchiness and
irritation associated with haemorrhoids. It contains the polymer propylene glycolpropylene glycol.
 Preparation H®Preparation H® Suppositories help shrink the haemorrhoidal tissue which is
swollen by irritation. It contains the polymer polyethylene glycolpolyethylene glycol.

INTRODUCTION
Anatomy of nose:-
• The nasal cavity consists of
passage of a depth of
approximately 12-14cm.
• The nasal passage runs
from nasal vestibule to
nasopharynx.

• The lining is ciliated, highly vascular and rich in mucus
gland.
• Nasal secretions are secreted by goblet cells, nasal
glands and transudate from plasma.
• It contains sodium, potassium, calcium, albumin,
enzymes like leucine,CYP450,Transaminase,etc.
• The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7
in infants.
INTRODUCTION

Advantages
• Large nasal mucosal surface area for dose absorption
• Rapid drug absorption via highly-vascularized
mucosa
• Rapid onset of action
• Ease of administration, non-invasive
Contd..

• Avoidance of the gastrointestinal tract and first-pass
metabolism
• Improved bioavailability
• Lower dose/reduced side effects
• Improved convenience and compliance
• Self-administration.
Advantages

Disadvantages
• Nasal cavity provides smaller absorption surface
when compared to GIT.
• Relatively inconvenient to patients when compared to
oral delivery since there is possibility of nasal
irritation.
• The histological toxicity of absorption enhancers
used in the nasal drug delivery system is not yet
clearly established.

Factors affecting nasal absorption
1. Molecular weight :-
• The nasal absorption of drugs decreases as the
molecular weight increases.
• Martin reported a sharp decline in drug absorption
having molecular weight greater than 1000 daltons.

2. Lipophilicity :-
• Absorption of drug through nasal route is
dependent on the lipophilicity of drugs.
• E.g. Alprenolol and Propranolol which are
lipophilic, has greater absorption than that of
hydrophilic Metoprolol.

3. pH of solution :-
• pH should be optimum for maximum absorption.
• Nonionised lipophilic form crosses the nasal epithelial
barriers via transcellular route and hydrophilic
ionized form passes through the aqueous paracellular
route.
• E.g. Decanoic acid shows maximum absorption at pH
4.5. Beyond this it decreases as solution becomes
more acidic or basic.

4. Drug concentration :-
• The absorption of drug through nasal route is
increased as concentration is increased.
• E.g. 1-tyrosine shows increased absorption at high
concentration in rate.

Pathway
• In systemic absorption the drugs generally get
diffused from epithelial cell into systemic
circulation.
• It is reported that nasal cavity have alternative
pathways of drugs absorption through
olfactory epithelium to CNS and peripheral
circulation.

Enhancement in absorption
• Following approaches used for absorption
enhancement :-
 Use of absorption enhancers
 Increase in residence time.
 Administration of drug in the form of microspheres.
 Use of physiological modifying agents

 Use of absorption enhancers:-
Absorption enhancers work by increasing the rate at
which the drug pass through the nasal mucosa.
Various enhancers used are surfactants, bile salts,
chelaters, fatty acid salts, phospholipids,
cyclodextrins, glycols etc.
Enhancement in absorption

Various mechanisms involved in absorption
enhancements are:-
• Increased drug solubility
• Decreased mucosal viscosity
• Decrease enzymatic degradation
• Increased paracellular transport
• Increased transcellular transport

 Increase in residence time:-
• By increasing the residence time the increase in
the higher local drug concentration in the mucous
lining of the nasal mucosa is obtained.
• Various mucoadhesive polymers like
methylcellulose, carboxymethylcellulose or
polyarcylic acid are used for increasing the residence
time.

 Administration of drug in the form of
microspheres:-
• Microspheres have good bioadhesive property and they
swell when in contact with mucosa.
• Microspheres provide two advantages-
a. Control the rate of clearance.
b. Protect drug from enzymatic degradation.
The microspheres of various materials showed
increased half-life of clearance. E.g. starch, albumin,
gelatin and dextran.

 Use of physiological modifying agents:-
• These agents are vasoactive agents and exert their
action by increasing the nasal blood flow.
• The example of such agents are histamine,
leukotrienene D4, prostaglandin E1 and β-
adrenergic agents like isoprenaline and terbutaline.

Nasal Delivery Systems
• They contain the drug in a liquid or powder
formulation delivered by a pressurized or pump
system.
• Various drug delivery systems are used for nasal drug
delivery.

 Liquid formulation :-
• These are usually aqueous solutions of the drug. The
simplest way to give a liquid is by nose drops.
• They are simple to develop and manufacture
compared to solid dosage forms but have a lower
microbiological and chemical stability, requiring the
use of various preservatives.

 Squeezed bottles :-
• These are used for nasal decongestant and work by
spraying a partially atomized jet of liquid into the
nasal cavity.
• They give a better absorption of drug by directing the
formulation into the anterior part of the cavity and
covering a large part of nasal mucosa.

 Metered-dose pump system :-
• They can deliver solutions, suspensions or emulsions
with a predetermined volume between 25 and 200 μL,
thus offering deposition over a large area.
• Particle size and dose volume are two important
factors for controlling delivery from metered-dose
systems.

• The optimum particle size for deposition in the nasal
cavity is 10μm.
• The volume of formulation that can be delivered is
limited by the size of the nasal cavity and larger
volumes tend to be cleared faster despite covering a
larger area.
• Better absorption is achieved by administering two
doses, one in each nostril, rather than a single large
dose.

Applications of Nasal Drug Delivery
A. Nasal delivery of organic based pharmaceuticals :-
• Various organic based pharmaceuticals have been
investigated for nasal delivery which includes drug
with extensive presystemic metabolism.
• E.g. Progesterone, Estradiol, Nitroglycerin,
Propranolol, etc.

B. Nasal delivery of peptide based drugs :-
• Nasal delivery of peptides and proteins is depend on:
 The structure and size of the molecule.
 Nasal residence time
 Formulation variables (pH, viscosity)
• E.g. Calcitonin, secretin, albumins, insulin, glucagon,
etc.
Applications of nasal drug delivery

Pulmonary Drug Delivery
System

• The lung is the organ of external respiration, in which
oxygen and carbon dioxide are exchanged between
blood and inhaled air.
• The structure of the airways prevent the entry of and
promotes the removal of airborne foreign particles
including microorganisms.
Contd..
Introduction

• The respiratory tract consists of conducting regions
(trachea, bronchi, bronchioles, terminal and
respiratory bronchioles) and respiratory regions
(respiratory bronchioles and alveolar regions).
• The upper respiratory tract comprises the nose, throat,
pharynx and larynx; the lower tract comprises the
trachea, bronchi, bronchioles and the alveolar
regions.
Contd..
Introduction

Contd..
Anatomy of pulmonary system

• Trachea branches into two main bronchi- the right
bronchus is wider and leaves the trachea at the
smaller angle than the left.
• The conducting airways are lined with ciliated
epithelial cells.
Anatomy of pulmonary system

Delivery systems
• Aerosols are used for the delivery of the drug by this
route of administration.
• The aerosols are defined as pressurized dosage from
containing one or more active ingredients which upon
actuation emit a fine dispersion of liquid or solid
materials in gaseous medium.

• There are three main types of aerosols generating
devices:-
i. Pressurized metered dose inhalers.
ii. Dry powder inhalers.
iii. Nebulizers.
Delivery systems

i. Pressurized metered dose inhalers:
• In pMDI’s, drug is either
dissolved or suspended in
liquid propellants together with other excipients and
presented in pressurized canister fitted with
metering valve.
• The predetermined dose is released as a spray on
actuation of the metering valve.
Delivery systems

• Containers:- Aerosol container must withstand
pressure as high as 140-180 psig at 130°F.
• Pharmaceutical aerosols are packaged in tin-plated
steel, plastic coated glass or aluminium containers.
• Aluminium is relatively inert and used uncoated where
there is no chemical instability between containers and
contents.
• Alternatively aluminium containers with an internal
coating of chemically resistant organic material such
as epoxy-resin or polytetrafluorine can be used
Delivery systems

• Propellants: These are liquified gases like
chlorofluorocarbons and hydrofluoroalkanes.
• These develop proper pressure within the container & it
expels the product when valve is opened.
• At room temperature and pressure, these are gases but
they are readily liquified by decreasing the temperature or
increasing pressure.
• The vapour pressure of the mixture of propellants is given
by Raoult’s law,
Contd…
Delivery systems

i.e. vapour pressure of the mixed system is equal to
the sum of the mole fraction of each component
multiplied by it’s vapour pressure.
p = pa + pb
where p = total vapour pressure of the system,
pa & pb = partial vapour pressures of the
components a & b.
Contd…
Delivery systems

• Metering valves:
It permits the reproducible delivery of small volumes of
product.
Depression of the valve stem allows the contents of the
metering chamber to be discharged through the orifice in
the valve stem and made available to the patient.
After actuation the metering chamber refills with liquid
from the bulk and is ready to dispense the next dose.
Delivery systems

ii. Dry powder inhalers:
In this system drug is inhaled as a cloud of fine
particles.
DPI formulations are propellant free and do not contain
any excipients.
They are breath activated avoiding the problems of
inhalation/actuation coordination encountered with
pMDI’s.
Delivery systems

iii. Nebulizers:
It delivers relatively large volume of drug solutions
and suspensions.
They are used for drugs that cannot be formulated into
pMDI’s or DPI’s.
There are three categories :-
a. Jet nebulizers
b. Ultrasonic nebulizers
c. Vibrating-mesh nebulizers
Delivery systems

a. Jet nebulizers:-
They are also called as air-jet or air-blast nebulizers
using compressed gas.
The jet of high velocity gas is passed tangentially or
coaxially through a narrow venturi nozzle typically
0.3 to 0.7 mm in diameter.
e.g. Pari LC nebulizer.
Delivery systems

b. Ultrasonic nebulizers:
In this the energy necessary to atomize liquids
come from the piezoelectric crystal vibrating at
high frequency.
c. Vibrating-mesh nebulizers:
In this device aerosols are generated by passing
liquids through a vibrating mesh or plate with
multiple apertures.
Delivery systems

Applications
• Smaller doses can be administered locally.
• Reduce the potential incidence of adverse systemic
effect.
• It used when a drug is poorly absorbed orally, e.g. Na
cromoglicate.
• It is used when drug is rapidly metabolized orally,
e.g. isoprenaline

1. IN VITRO / EX VIVO METHODS
a. Methods based on measurement of tensile strength.
b. Methods based on measurement of shear strength.
OTHER IN VITRO METHODS
c. Adhesion weight method
d. Fluorescent probe method
e. Flow channel method
f. Falling liquid film method
g. Colloidal gold staining method
h. Mechanical spectroscopic method
i. Thumb test
j. Viscometric method
k. Adhesion number
l. Electrical conductance
2. IN VIVO METHODS
a. Use of radio isotopes
b. Use of gamma scintigraphy
115

In vitro/ex vivo tests are important in the development of a
controlled release bioadhesive system because they contribute to
studies of
1. Permeation
2. Release
3. Compatibility
4. Mechanical and physical stability
5. Superficial interaction between formulation and mucous
membrane; and
6. Strength of the bioadhesive bond.
These tests can simulate a number of administration routes
including oral, buccal, periodontal, nasal, gastrointestinal,
vaginal and rectal.
116
IN VITRO/ EX VIVO TESTS

117
DETERMINATION 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
118

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
119
MEASUREMENT OF DETACHMENT FORCE
Mucoadhesion by modified balance method

120
Measurement of mucoadhesive tensile strength
with an automatic surface tensiometer.

Equipment used: Texture analyzer or universal testing machine
In this test, the force required to remove the formulation from a model
membrane is measured, which can be a disc composed of mucin, a piece
of animal mucous membrane.
Based on results, a force-distance curve can be plotted which yields the
force required to detach the mucin disc from the surface with the
formulation, the tensile work (area under the curve during the
detachment process), the peak force etc.
This method is more frequently used to analyze solid systems like
microspheres, although there are also studies on semi-solid materials
121
MEASUREMENT OF RUPTURE TENSILE
STRENGTH

This test measures the force required to separate two parallel glass slides
covered with the polymer and with a mucus film
Eg: Wilhelmy plate method
Glass plate is suspended by a microforce balance and immersed in a
sample of mucus under controlled temperature.
The force required to pull the plate out of the sample is then measured
under constant experimental conditions
Although measures taken by this method are reproducible, the technique
involves no biological tissue and therefore does not provide a realistic
simulation of biological conditions
123
MEASUREMENT OF SHEAR STRENGTH

Adhesion weight method
Adhesion number
Falling liquid film method
Fluorescent probe method
Flow channel method
Mechanical spectroscopic method
Electrical conductance
Colloidal gold staining method
Thumb test
Viscometric method
125
OTHER IN VITRO METHODS

Particles are allowed to come in contact with the mucosal membrane for a
short period of time (around 5 mins)
The weight of particles retained is then measured
Good method for determination of effect of various parameters such as
particle size, charge etc on mucoadhesion
Limitations:
1. Poor data reproduciblity
2. Rapid degenration of mucosal tissue
126
ADHESION WEIGHT METHOD

Applicable for small particles eg. Mucoadhesive microparticles
Particles are allowed to come in contact with the mucosal membrane for a
short period of time (around 5 mins)
The number of particles retained is then measured
127
ADHESION NUMBER
100
0
X
N
N
Na =
Na – Adhesion number
N – number of particles
attached to the substrate
N0 – total number of particles
under test

The chosen mucous membrane is placed in a stainless steel cylindrical tube,
which has been longitudinally cut.
This support is placed inclined in a cylindrical cell with a temperature
controlled at 37 ºC.
An isotonic solution is pumped through the mucous membrane and collected
in a beaker
Subsequently, in the case of particulate systems, the amount remaining on
the mucous membrane can be counted with the aid of a coulter counter
The validation of this method showed that the type of mucus used does not
influence the results
128
FALLING LIQUID FILM METHOD

Study polymer interaction with mucosal membrane using fluorescent
probes
The mucus is labeled with pyrene or fluorescein isothiocyanate
It is then mixed with the bioadhesive material
The changes in fluorescence spectra is monitored
130
FLUORESCENT PROBE METHOD

It utilises a thin channel made of glass filled with aqueous solution of
mucin thermostated at 37°C.
Humid air at the same temperature is passed through the glass channel
A particle of bioadhesive polymer is placed on the mucin gel
Its static and dynamic behavior can be monitored at frequent intervals
using a camera
131
FLOW CHANNEL 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
132
MECHANICAL SPECTROSCOPIC 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
133
ELECTRICAL CONDUCTANCE METHOD

It employs red colloidal gold particles which were stabilized by adsorbed
mucin molecules
Upon interaction with these mucin-gold conjugates, bioadhesive materials
develop a red colour on the surface
This interaction can be quantified by measuring the intensity of the red
colour
134
COLLOIDAL GOLD STAINING NUMBER

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
135
THUMB TEST

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
136
VISCOMETRIC METHOD

ηb – bioadhesion component
ηt - coefficient of viscosity of the system
ηm and ηp - coefficients of viscosity of mucin and bioadhesive polymer,
respectively
All components should be measured at the same concentration,
temperature, time and shear gradient.
The bioadhesion force, F, is determined by equation:
where is the shear gradientσ
The main disadvantage of this method is the breakdown of the polymer
and mucin network under continuous flow
137

The everted gut sac technique is an example of an ex vivo method
It has been used since 1954 to study intestinal transport
It is easy to reproduce and can be performed in almost all laboratories.
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
138
USING EVERTED GUT SAC OF RATS

Use of radioisotopes
Use of gamma scintigraphy
Use of pharmacoscintigraphy
Use of electron paramagnetic resonance(EPR) oximetry
X ray studies
Isolated loop technique
140
IN VIVO METHODS

In vitro drug release
In vitro drug permeation – Franz diffusion cell, Keshary Chein cell,
modified Franz diffusion cell
Histopathological evaluation of mucosa after prolonged contact with
bioadhesive material
Other tests for that dosage form eg. Tablets, microparticles etc maybe
applicable
141
OTHER EVALUATION PARAMETERS

PRODUCT COMPANY BIOADHESIVE AGENT PHARMACEUTICAL
FORM
Buccastem® Reckitt Benckiser PVP, Xanthum gum Buccal tablet
Corlan pellets® Celltech Acacia gum Oromucosal pellets
Suscard® Forest HPMC Buccal tablet
Gaviscon liquid® Reckitt Benckiser Sodium alginate Oral liquid
Orabase® Convatech Pectin, Gelatin Oral paste
Corsodyl gel® GalaxoSmithKline HPMC Oromucosal gel
Pilogel Alcon Carbomere Eye ge
Timoptol Merk, sharpe and Dohme Gallan gum Eye gel forming solution
Aci- jel Janssen- cilag Tragacanth Vaginal gel
Crinone Serono Carbomer Vaginal gel
Gynol Janssen- cilag Sod. CMC & PVP Vaginal gel
Zidoval 3M Carbomer Vaginal gel
Nyogel® Novartis Carbomer and PVA Eye gel
Currently available bioadhesive formulation in U.K.
142

143
REFERENCES
Bioadhesive drug delivery systems fundamentals, Novel approaches, and
development: edited by Mathiowitz, Donald E. Chickering III, Claus-Michael
lehr, Vol-98, Page no-1-6,131-145,507-541, 541-563,601-641.
Roop K Khar, S.P Vyas, Controlled drug delivery concept & advances, 1st
edition, page no-250-313.
Harris .D, Robinson.J.R. Drug delivery via the mucous membranes of oral
cavity,J. Pharma. Sci , vol-81, 1992 Page no-1-8.
Ahuja.a, Khar.R.K and Ali.J, Mucoadhesive Drug Delivery Systems, Drug Dev.Ind.
Pharm,23, 1997, 489-515.
Lee J.W, Park J.H, Robinson J.R, Bioadhesive-Based Dosage Forms: The Next
Generation, J Pharm Sci. vol- 89, 2000, 850-861.
Chidambaram.N & Srivastava A.K, Buccal drug delivery systems, Drug Dev.Ind.
Pharm, 21, 1995, 1009-1036.

144
Kockisch.S, Rees.G.D, Young.S.A, polymeric microspheres for drug delivery
to oral cavity:An in vitro evaluation of mucoadhesive potential, J Phama Sci,
Vol-92, 2003, page no-1614.
Mizrahi.B, Adhesive tablets effective for treating canker sores in human, J
Phama Sci, Vol-93, 2004, page no-2927.
M.J Rathbone, J. Handgraft, M.S. Roberts, Modified Drug Delivery, Vol-126,
Page no-447,463.
H.S Ch’ng, H. Park, P. Kelly, J.R.Robinson,Bioadhesive polymers as a
platforms for oral controlled drug delivery II: Sythesis & evaluation of some
swelling water insoluble polymers, J Pharma Sci,74, 1985,page no- 399.
K.R. Kamath, K. Park, Mucosaladhesive preprations, Encyclopedia of
Pharmaceutical Technology,(J. Swarbick, J.C Boylan)Marcel Dekker, 1994,
page no 133.

145
Shah K. U. and. Rocca J. G ,Lectins as Next-Generation
Mucoadhesives for Specific Targeting of the Gastrointestinal Tract,Drug
delivery tech.com
Moes .A.J, Gastric retention system for oral drug delivery, Drug
delivery oral, Business Briefings, pharmatech –2003,
www.bbriefings.com/pdf/890/Pt04_moes.pdf
Batchelor .H, Novel Bioadhesive Formulations in Drug Delivery, The
drug delivery companies report autumn/winter2004, Pharma Ventures Ltd
2004, page no-16-19, www.worldpharmaweb.com/ddcr/auto4/article7.pdf
Collins .A.E & Deasy. B.D, Bioadhesive lozenges for the improved delivery of
cetyl pyridinium chloride, J. Pharm. Sci, Vol-79,1990, Page NO-116-119.
James Swarbick, James C Boylan,Encyclopedia of pharmaceutical
technology,vol-2, 1994, Page no-189-205.

146
 Give the definitions and importance of BDDS.
 Theories of bioadhesion
 Which are the factors important to bioadhesion?
 Give classifications of BDDS.
 Write note on Buccal BDDS with its advantages and
limitations.
 How will you do the evaluation of bioadhesive drug
delivery systems?
QUESTIONS

Thank you…!!!Thank you…!!!

MUCOADHESIIVE DRUG DELIVERY SYSTEM

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