Bio adhesive dds

glimpses of bio adhesive delivery systems

1. BIOADHESIVE DRUG BIOADHESIVE DRUG
DELIVERY SYSTEMDELIVERY SYSTEM
RAGHAVENDRA KUMAR GUNDA
M.PHARM
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2. BIOADHESION:-
• Bioadhesion can be defined as a phenomenon of interfacial
molecular attractive forces amongst the surfaces of the biological
substrate and the natural or synthetic polymers, which allows the
polymer to adhere to the biological surface for an extended period of
time.
•The two term bioadhesive and the mucoadhesive are similar except
in term of the site of adhesion.
2

3. Bioadhesive Polymer :-Bioadhesive Polymer :-
A polymer is a substance formed by the linkage of a large number of
small molecules known as monomers. A bioadhesive polymer is a
synthetic or natural polymer which binds to biological substrates such
as mucosal membrane. Such polymers are sometimes referred to as
biological ‘glues’ because they are incorporated into drugs to enable
the drugs to bind to their target tissues
3

4. Mucosal membranes:-Mucosal membranes:-
These are moist membranes that line passageways and structures in
the body that lead to the outside environment such as the mouth,
respiratory tract, gastrointestinal tract, nose and vagina. They
secrete a viscous fluid known as mucus, which acts as a protective
barrier and also lubricates the mucosal membrane. The primary
constituent of mucus is a glycoprotein known as mucin as well as
water and inorganic salts.
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5. HISTORY:-
Bioadhesive drug delivery formulations were introduced in 1947 when gum
tragacanth was mixed with dental adhesive powder. The aim was to deliver
Penicillin into the oral mucosa. This later became Orabase®, a formulation used to
treat mouth ulcers. This product is available as a paste which will stick to the wet
surfaces of the mouth and form a protective film over the mouth ulcer. Orabase
paste contains polymers such as gelatin, pectin and Carboxymethylcellulose.
Some examples of Orabase products are shown belowSome examples of Orabase products are shown below
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6. BIOADHESIVE POLYMER:-
Bioadhesive polymers come from both natural and synthetic sources, some
common examples are highlighted below:
Acacia gum -Acacia gum - This natural polymer is a dried gum obtained from the stem and
branches of the tree Acacia senegal. It is used as a thickener in pharmaceuticals.
Alginic acid – Alginic acid – Is a natural polymer found in the cell walls of brown algae. It is
widely used in the manufacture of alginate salts such as sodium alginate which is
a
constituent of Gaviscon liquid®.
Carbomers –Carbomers – Are polyacrylic acid polymers widely used in the pharmaceutical and
cosmetic industries as thickening agents.. Carbomers have a huge advantage in
formulation science because they adhere strongly to mucosal membranes without
causing irritation, they exhibit low toxicity profiles and are compatible with many

drugs.
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7. CONT…….CONT…….
Hydroxypropyl methylcellulose (HPMC) – Hydroxypropyl methylcellulose (HPMC) – This polymer is included in
preparations used to moisten contact lenses and in oral gels.
Sodium hyaluronate -Sodium hyaluronate - A high molecular weight biological polymer made
of
repeating disaccharide units of glucuronic acid and N-acetyl-D –
glucosamine. This polymer is used during intraocular surgery to protect the

cornea and also acts as a tear substitute in the treatment of dry eyes.
Other examples of polymers include:
- - pectinpectin
- - polyvinylalcohol (PVA)polyvinylalcohol (PVA)
- polyvinylpyrrolidone (PVP)polyvinylpyrrolidone (PVP)
- - tragacanthtragacanth
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8. MECHANISMS OF BIOADHESION:-MECHANISMS OF BIOADHESION:-
•The mechanisms responsible in the formation of bioadhesive bonds are not
fully known.
•Most research has focused on analysing the bioadhesive interactions Most research has focused on analysing the bioadhesive interactions
between polymer hydrogel and soft tissue.between polymer hydrogel and soft tissue.
I.Wetting and swelling of polymer
II.Interpenetration between the polymer chains and the mucosal membrane
III.Formation of chemical bonds between the entangled chains
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9. Step 1:-Step 1:-
The wetting and swelling step occurs when the polymer spreads over the
surface of the biological substrate or mucosal membrane in order to
develop an intimate contact with the substrate. This can be readily
achieved for example by placing a bioadhesive formulation such as a
tablet or paste within the oral cavity or vagina. Bioadhesive 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.
The image below shows swelling of a polymer The image below shows swelling of a polymer
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10. Step 2:-Step 2:-
The surface of mucosal membranes are composed of high molecular weight
polymers known as glycoproteins. In step 2 of the bioadhesive bond
formation, the bioadhesive polymer chains and the mucosal polymer chains
intermingle and entangle to form semi permeable adhesive bonds. The
strength of these bonds 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.
The interpenetration of polymer chainsThe interpenetration of polymer chains
Bioadhesive
polymer chains
Mucus
polymer chains
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11. Step 3:-Step 3:-
This step involves the formation of weak chemical bonds between the
entangled polymer chains. The types of bonding formed between the chains
include primary bonds such as covalent bonds and weaker secondary
interactions such as Vander Waals Interactions and hydrogen bonds. Both
primary and secondary bonds are exploited in the manufacture of
bioadhesive formulations in which strong adhesions between polymers are
formed.
Mechanisms of bioadhesion Mechanisms of bioadhesion
Step 3Step 3
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12. Ideal polymer characteristics for Bioadhesion:-
•Sufficient quantity of the hydrogen binding chemical groups.
•Anionic surface charges.
•High molecular weight.
•High chain flexibility
•Surface tension.
These are helpful in formation of bond which are either…
1.Chemical bonds
2.Mechanical or Physical bond
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13. THEORIES OF MUCOADHESION:-
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14. Types of bioadhesive drug delivery system:-Types of bioadhesive drug delivery system:-
1.Solid Bioadhesive Formulations1.Solid Bioadhesive Formulations:
Examples of such formulations are given below.
Tablets :Tablets : Dry formulations such as tablets are able to form strong
interactions with mucosal surfaces by attracting water from the
mucosal surface. An example is Buccastem® which is used in the
treatment of nausea, vomiting and vertigovertigo. It is administered to the
buccal mucosa (inside of the cheeks).
Inserts: Inserts: These include ocular inserts such as eye drops and eye gels. An
example is Pilogel® which is used in the treatment of glaucoma
(raised pressure in the eye). Pilogel® contains the bioadhesive agent
carbomer 940,which minimises irritation and prevents the loss of
product by keeping the gel in place.
Lozenges: Lozenges: Bioadhesive lozenges containing antibiotics and local
anaesthetics can be used topically to treat conditions affecting the
mouth. Research has shown that bioadhesive lozenges are able to
release drugs in a controlled manner by prolonging the drug release.

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15. 2. Semi-solid bioadhesive Formulations:-2. Semi-solid bioadhesive Formulations:-
Gels :Gels :Bioadhesive polymers that are able to form gels include polyacrylic polyacrylic
acidacid which adheres to mucosal surfaces in a cross-linked form. Gel
formulations are used to target several parts of the body including the

eye, vagina and oral cavity. An advantage of gels is that they are able

to form a very close contact with mucosal membranes and rapidly
release drugs at their site of absorption.
Films:Films: Bioadhesive films that are flexible in nature can be used to directly
deliver drugs to specific mucosal membranes. They form a very
close contact with the membrane and are able to deliver an accurate
dose of drug to the site of absorption. An example of a bioadhesive
film is Zilactin® which is used in the treatment of cold sores and
mouth ulcers.
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16. 3.Liquid Bioadhesive Formulations:-3.Liquid Bioadhesive Formulations:-
Viscous liquids:Viscous liquids: Viscous liquids containing bioadhesive polymers such as
carboxymethyl cellulose may be used to protect mucosal membranes from
damage and irritation. They can also be used to deliver drugs to specific
sites. An example is artificial tears, a carbomer solution used to treat dry
eyes.
Gel-forming liquids:Gel-forming liquids: These formulations are administered as liquids but
undergo a change in their form in response to conditions such as
temperature and pH. Such formulations are used for the controlled-release
of drugs into the eye.
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17. Bioadhesive or mucoadhesive
formulations have been targeted to
various anatomical locations to
aid drug delivery and absorption.
These structures possess mucous
membranes which protect the cell
from damage. Drug delivery to
each anatomical region is
discussed below.
Body siteBody siteSystemsSystems
Eye Mucoadhesive
eye drops /
inserts
Nasal cavity Nasal drug
delivery systems
Oral cavity Dental gels /
buccal systems
Skin Patches, tapes,
dressings
Vagina Local vaginal
delivery systems
Rectum Local/systemic
rectal delivery
systems
Targets for Bioadhesive Formulations:-Targets for Bioadhesive Formulations:-
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18. 1
8
TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:-FORMULATIONS:-
1.1.The eye:-The eye:-
The eye is one of the most important and complex organs of the body, because of
its complicated anatomy many things can go wrong with the eye. Topical drug
delivery systems to the eye can be very difficult to achieve because the eye has
several protective mechanisms in place to get rid of foreign substances.

A brief anatomy of the eyeA brief anatomy of the eye
An effective ocular drug delivery system must
be easy to use, comfortable to the patient
and maintain substantial concentrations of
the drug in the eye to produce therapeutic
effects.

19. SOME CONDITIONS OF THE EYE:-SOME CONDITIONS OF THE EYE:-
Conjunctivitis – Conjunctivitis – This is an inflammation of the conjunctivae, which are mucous
membranes covering the whites of the eye and the inside of the eyelids. It is
caused by bacteria, viruses or allergens and the signs and symptoms displayed by
the patient will be dependent on the type of conjunctivitis. The symptoms
include: redness of the eye, grittiness or itchy eyes and the presence of a sticky
or watery discharge.
Dry eye – Dry eye – This occurs when people don’t have enough tears or the adequate
composition of tears required to lubricate the eyes. The occurrence of dry eye
increases with age and is therefore common in older people. The eyes become
itchy, gritty, painful and have a burning sensation.
Glaucoma – Glaucoma – This disorder is characterised by pressure in the eyeballs and causes
excessive amounts of aqueous humouraqueous humour (the fluid that fills the eyeballs). This
puts pressure on the optic nerves and compresses the blood vessels in the eye.
The resultant effects include abnormalities in vision and total blindness.
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20. OCULAR BIOADHESIVE
FORMULATIONS:-
Various ocular bioadhesive formulations have been designed to treat specific
conditions affecting the eye. Such formulations can produce a prolonged or
sustained release of drugs into the eye. Drugs containing polymers attach to the
mucinmucin on the conjunctival surface by means of non-covalent bonding. The polymer
is able to remain in contact with the surface of the eye until mucin replaces itself or
until the pressure of blinking removes the drug from the eye.
EXAMPLES OF PRODUCTSEXAMPLES OF PRODUCTS
HypotearsHypotears® ® and Sno Tears® Sno Tears® Eye drops are used for dry eye and tear
deficiency and they generally lubricate the eyes. They both contain the polymer
polyvinyl alcohol (PVA) which increases tear production and protects the eye
from further irritation.
The monomer from which
PVA is made Vinyl alcohol

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21. OCULAR BIOADHESIVE FORMULATIONS:-
GelTearsGelTears® and Viscotears® ® and Viscotears® Liquid gel eye drops are used for dry eye
conditions and contain carbomer 980 (polyacrylic acid). Carbomers lubricate the
eye by clinging to the surface of the eye. This can help reduce the frequency of
their application into the eye.
Pilogel® Pilogel® Is an eye gel used in the treatment of glaucoma. It contains the high
molecular weight polymer polyacrylic acid. The polymer increases the viscosity
of the gel which provides a prolonged retention of the gel in the eye.
POLYACRYLIC ACIDPOLYACRYLIC ACID

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22. TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:-FORMULATIONS:-
2. The Nasal Cavity2. The Nasal Cavity
The nasal cavity is the air passage behind the nose. This is the source of the
moisture which is added to air during the breathing process. The nasal cavity has a
complex structure and can become inflamed during conditions such as the common
cold, nasal allergies and flu.
Drugs such as antihistamines and steroids are administered as nasal drops or nasal
sprays to treat conditions affecting the nose. However nasal mucociliary clearancemucociliary clearance
affects the retention and therefore the effects of the drugs in the nose.
Mucociliary clearance transports mucus from the cells
lining the nose and protects the respiratory tract from
damage caused by inhaled substances including
dirt particles and medicines.

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23. NASAL BIOADHESIVE FORMULATIONS:-NASAL BIOADHESIVE FORMULATIONS:-
By mixing drugs targeted for the nose with bioadhesive polymers, the process of
mucociliary clearance of the drug can be overcome. The effects of bioadhesive
polymers on mucociliary clearance was examined by Zhou and DonovanZhou and Donovan (1996).
All the polymers examined showed decreases in mucociliary clearance.
Methylcellulose exhibited the most reduction in mucociliary clearance whilst
Carbopol 934P showed the least reduction in mucociliary clearance in the rats used.
EXAMPLES OF PRODUCTS EXAMPLES OF PRODUCTS
RhinocortRhinocort®® Nasal spray is a powdered mixture of the steroid Beclomethasone
dipropionate (50μg) and 30mg of Hydroxypropyl cellulose(HPC). Patients
suffering from nasal allergy administer one spray twice a day into the nasal
cavity.The powder sticks to and swells on the cells lining the nose and remains
there until approximately six hours after administration.
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24. NASAL BIOADHESIVE NASAL BIOADHESIVE
FORMULATIONS:- FORMULATIONS:-
BeconaseBeconase® ® Nasal spray is used to treat nasal inflammation and nasal allergies
associated with hay fever. It contains the active ingredient Beclometasone
dipropionate and the bioadhesive polymers carboxymethyl cellulose and carboxymethyl cellulose and
microcrystalline cellulose. microcrystalline cellulose.
Nasacort® Nasacort® Nasal spray is used to treat allergies that result in inflammation of
the nose. The active ingredient in this product is Triamcinolone acetonide as well
as the bioadhesive polymer microcrystalline cellulosemicrocrystalline cellulose. The polymer swells in the
presence of water and is able to spread across the nasal mucosa thus helping the
distribution of the drug over the mucosal surface.
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25. TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:- FORMULATIONS:-
3. The oral cavity3. The oral cavity
The oral cavity or the mouth comprises of the cheeks, hard and soft palates and
the tongue. It is an entrance of the digestive system and plays many important
functions which include chewing, speaking and tasting. Some of these functions
are impaired by diseases such as ulcers, microbial infections and inflammation.
Some of the common conditions affecting the oral cavity are discussed on the
next slide.


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26. COMMON CONDITIONS AFFECTING THE ORAL
CAVITY
Mouth ulcers : Mouth ulcers : A mouth ulcer can be described as a breach or break
in the mucous membrane that lines the inside of the mouth. The
majority of patients suffer from minor aphthous ulcers (MAU). These
ulcers are roundish, shallow, grey-white in colour and are painful.
They are small and appear in small crops.
Oral thrush:Oral thrush: This is an infection caused by the fungus Candida Candida
albicansalbicans in the oral cavity. It can also arise due to risk factors such as
diabetes, recent antibiotic therapy and inhaled corticosteroids. Oral
thrush presents itself as soft creamy-white patches which can be
wiped off. The lesions are painful and can occur anywhere in the oral
cavity.
Gingivitis:Gingivitis: Gingivitis means inflammation of the gums. It is caused
by the build-up of plaque (a layer of bacteria) on the teeth. The gums
become reddened, swollen and bleed easily with slight trauma such as
brushing the teeth.

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27. 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.
EXAMPLES OF PRODUCTSEXAMPLES OF PRODUCTS
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
Acacia Acacia 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.
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28. 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 pregelatinised
potato starchpotato 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 Hydroxypropyl
cellulose(HPC)cellulose(HPC) which helps retain the gel inside the oral cavity.
28

29. TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:-FORMULATIONS:-
3a.The Buccal Mucosa3a.The Buccal Mucosa
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 permeable compared to other oral drug delivery
systems and is unable to retain dosage forms at the site of absorption. The
use of bioadhesive polymers in buccal drug delivery systems allows a better
retention of a dosage form by spreading it over the absorption site.
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).
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30. TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:-FORMULATIONS:-
3b. The sublingual mucosa3b. The sublingual mucosa
The sublingual mucosa surrounds the sublingual gland which is a mucin-
producing salivary glandsalivary gland located underneath the tongue.
This mucosa is relatively permeable and gives a rapid absorption of many
drugs due to its excellent blood supply. The sublingual route of drug delivery
is convenient, accessible and generally well accepted by patients.
Drugs administered via the sublingual route are formulated as tablets, powders,
solutions or aerosol sprays. This route is appropriate for many drugs as long
as the drug is able to go into solution with saliva in the mouth.
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.

30

31. TARGETS FOR BIOADHESIVE
FORMULATIONS:-
4.The Skin4.The Skin
The skin is the outer covering of the body and consists of different layers.It
performs several functions which include:
Protecting the body from injury and invasion by pathogens
Preventing the body from becoming dehydrated
Regulating body temperature
Production of Vitamin D

Cross section of the skinCross section of the skin
31

32. TOPICAL BIOADHESIVE FORMULATIONS:-
The drug delivery systems used in this case are required to adhere to the skin for
the purpose of:
Collecting body fluids
Protecting the skin
Providing local or systemic drug delivery
Adhesion can be described as the formation of a new mechanical bond between
the skin and the adhesive agent. Bioadhesive products targeted to the skin are
formulated into different dosage forms which include liquids, powders and
semi-solids such as ointments and transdermal patches.

Transdermal patches are sustained-release devices that release a specific amount of
drug whilst firmly attached to the skin. They must provide a firm, soft contact with
the skin but also allow the patch to be easily removed with minor effort.
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33. TOPICAL BIOADHESIVE
FORMULATIONS:-
Examples of ProductsExamples of Products
VoltarolVoltarol® Emulgel: ® Emulgel: This is a gel which provides a local relief from
pain and inflammation in the tendons, muscles and joints. It contains
the bioadhesive polymer carbomercarbomer which aids the absorption of the
active drug by spreading it into the affected area.
Feldene®:Feldene®: This gel is used in the treatment of conditions which are
characterised by pain, inflammation and stiffness. The active
ingredient in this formulation is piroxicampiroxicam but the gel also contains
two bioadhesive agents to increase its retention at the absorption site.
These agents are Carbopol 980Carbopol 980 and hydroxyethyl cellulose.hydroxyethyl cellulose.
Evorel®: Evorel®: Is a patch used in hormone replacement therapy (HRT) for
oestrogen deficiency. It consists of an adhesive matrix through which
the active drug (estradiol) is evenly distributed. The adhesive
polymers used are guar gumguar gum and polyacrylic acid polyacrylic acid which holds the
patch firmly on the skin surface.
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34. TARGETS FOR BIOADHESIVE TARGETS FOR BIOADHESIVE
FORMULATIONS:- FORMULATIONS:-
5. The Vagina5. The Vagina
The vagina is the lower part of the female reproductive tract. It is a muscular
tube lined with mucous membrane which is covered with a layer of stratified stratified
squamous epitheliumsquamous epithelium with an underlying layer of connective tissue (lamina lamina
propriapropria) .
Histology of the vaginal mucosaHistology of the vaginal mucosa The female reproductive System The female reproductive System
34

35. COMMON CONDITIONS AFFECTING THE
VAGINA:-

The epithelium of the vagina contains glycogenglycogen, which is broken down enzymes
and bacteria into acids such as lactic acid. This maintains a low vaginal pH
which is normally between 4 and 5.
Such a pH is desirable because it makes the vagina inhospitable to pathogens.
Decreased levels of glycogen in the vagina leads to an increase in vaginal pH
and makes the vagina more susceptible to infection.
Common vaginal infectionsCommon vaginal infections
Vaginitis :Vaginitis : Vaginitis means inflammation of the vagina and it creates discharge,
odour, irritation or itching. It has many causes which includes infection with
Trichomonas vaginalis, Trichomonas vaginalis, dietary deficiency or poor hygiene.
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36. COMMON CONDITIONS AFFECTING THE
VAGINA:-
Bacterial vaginosis: Bacterial vaginosis: The causal organism often implicated in C. albicansC. albicans
this infection is Gardnerella vaginalisGardnerella vaginalis, although other bacteria
present in the vagina also contribute to the cause. The infection
arises due to the overgrowth of these bacteria. About 50% of
patients will have a thin white discharge with a strong fishy odour.
Candidiasis (Thrush):Candidiasis (Thrush): Is a common yeast infection caused
by the organism Candida albicansCandida albicans. The signs and symptoms
of thrush are a white cheesy discharge that itches and irritates
the vagina. T. vaginalisT. vaginalis
Trichomoniasis: Trichomoniasis: Is a sexually - transmitted infection caused
by the organism Trichomonas vaginalisTrichomonas vaginalis. The symptoms in
women include vaginal itching as well as a frothy, foul-smelling,
greenish-yellow discharge.
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37. VAGINAL BIOADHESIVE
FORMULATIONS:-
The intravaginal route has been used to deliver contraceptives as well as
anti-infective agents such as antifungal drugs to exert a local effect. Agents
targeted for the vaginal route have been formulated into various dosage forms
including creams, gels and vaginal tablets.
Localised application of vaginal formulations enables the spread of these
formulations over the target area, which allows an effective therapy.
Bioadhesive polymers are incorporated into vaginal formulations to aid the
adhering of the dosage form to its target site. Polymers also increase the retention
of the active drug in the vagina and also optimises the spread of the formulation
over the vaginal epithelium.
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38. VAGINAL BIOADHESIVE FORMULATIONS:-
ProductProduct Function of ProductFunction of ProductBioadhesive AgentBioadhesive Agent DosageDosage
FormForm
Aci-Jel® Maintains vaginal
acidity
Acacia, Tragacanth Vaginal Gel
Crinone® Used for
Progesterone
deficiency
Carbomer Vaginal Gel
Estring® Restores Oestrogen
deficiency
Silicone Polymers Vaginal
Ring
Gynol-II® Spermicidal
Contraceptive
Carboxymethyl
cellulose
Vaginal
Gel
Zidoval® Treatment of
bacterial
vaginosis
Carbomer Vaginal
Gel
Examples of vaginal products:- Examples of vaginal products:-
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39. TARGETS FOR BIOADHESIVE
FORMULATIONS:-
6.The Rectum6.The Rectum
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.

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40. RECTAL BIOADHESIVE FORMULATIONS:-
Bioadhesive polymers are incorporated into rectal suppositories to prolong the
retention of the active drug in the rectum. Prolonged retention in the rectum
increases the chances of reaching a therapeutic outcome.
EXAMPLES OF PRODUCTSEXAMPLES OF PRODUCTS
AnacalAnacal® ® Is a rectal ointment used to relieve the symptoms associated with
hemorrhoids. 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.
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41. TECHNIQUES FOR EVALUATING BIOADHESIVE
PROPERTIES:-
1.In vitro techniques:-
•Tensile stress measurement:-
1. Wilhelmy plate technique:
The Wilhelmy plate technique is traditionally used for the measurement of dynamic
contact angles. The instrument measures the bioadhesive force between mucosal
tissue and the dosage form. By using the CAHN software system, parameters such
as fracture strength, deformation to failure and work of adhesion can be analysed.
41

42. 2. Electromagnetic force transducer (EMFT):
The EMFT uses a calibrated electromagnet to detach a magnetic loaded polymer
DDS from a tissue sample. It has the unique ability to record remotely and
simultaneously the tensile force information as well as high magnification video
images of bioadhesive interactions at near physiological conditions.EMFT
measures tissue adhesive forces by monitoring the magnetic force required to
exactly oppose the bioadhesive force.
3. Texture analyzer:-
•Shear stress measurement:-
The shear stress technique measures the force that causes a mucoadhesive to slide
with respect to the mucous layer in a direction parallel to their plane of contact.
Adhesion tests based on the shear stress measurement involve two glass slides
coated with polymer and a film of mucus.
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43. •Rheological approach:-
The rheological properties of the mucoadhesive interface (i.e. of the hydrated gel) are
influenced by the occurrence of interpenetration step in the process of bioadhesion.
Chain interlocking , conformational changes and chemical interaction, which occur
between bioadhesive polymer and mucin chains, produce changes in the rheological
behaviour of the two macromolecular species. The rheological studies provide an
acceptable in vitro model representative of the in vivo behaviour of mucoadhesive
polymers.
•Colloidal gold staining method:-
This technique employs red colloidal gold particles, which are stabilized by the
adsorbed mucin molecule by forming mucin– gold conjugates [55]. Upon
interaction with mucin–gold conjugates, bioadhesive hydrogels develop a red colour
on the
surface. Thus, the interaction between them can easily be quantified, either by the
measurement of the intensity of the red colour on the hydrogel surface or by the
measurement of the decrease in the concentration of the conjugates from the
absorbance changes at 525 nm. 43

44. •Viscometeric method:-
A simple viscometric method was used by Hassan and Gallo to quantify mucin–
polymer bioadhesive bond strength. Viscosities of 15 %w/v porcine gastric mucin
dispersion in 0.1M HCl (pH 1) or 0.1M acetate buffer (pH 5.5) were measured with
a Brookefield viscometer in the absence or presence of selected neutral, anionic,
and cationic polymers. Viscosity components and the forces of bioadhesion were
calculated.
•Fluorescent probe method:-
Park and Robinson studied polymer interaction with the conjunctival epithelial cell
membrane using fluorescent probes. The membrane lipid bilayer and membrane
proteins were labelled with pyrene and fluorescein isothiocyanate, respectively. The
cells were then mixed with candidate bioadhesive, and the changes in fluorescence
spectra were monitored. This gave a direct indication of polymer binding and its
influence on polymer adhesion
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45. In vivo techniques:-
GI transit using radio-opaque technique
It involves the use of radio-opaque markers, e.g., barium sulfate, encapsulated in
bioadhesive DDS to determine the effects 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. Mucoadhesive labelled with Cr-51, Tc-99m,
In-113m, or I-123 have been used to study the transit of the DDS in the GI tract.
Gamma scintigraphy technique:-
It is a valuable tool used in the development of pharmaceutical dosage forms. With
this methodology, it is possible to obtain information non-invasively.
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46. Case studies:- Design and evaluation of novel pH-sensitive
chitosan nanoparticles for oral insulin delivery
•Chitosan nanoparticles (CS NPs) have been commonly regarded as potential
carriers for the mucosal delivery of therapeutic peptides because of their
biocompatibility, bioadhesion and permeation enhancing properties. However,
they
have limited colloidal stability and readily dissociate and dissolve in the acidic
gastric conditions
•CS NPs were formulated by ionic cross-linking with hydroxypropyl
methylcellulose phthalate (HPMCP) as a pH-sensitive polymer and evaluated for
the oral delivery of insulin.
•In vitro results revealed a superior acid stability of CS/HPMCP NPs with a
significant control over insulin release and degradation in simulated acidic
conditions with or without pepsin.
•Following peroral administration, CS/HPMCP NPs increased the hypoglycemic
effect of insulin by more than 9.8 and 2.8-folds as compared to oral insulin
solution
and insulin-loaded CS/ tripolyphosphate (TPP) NPs, respectively.
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47. In vitro release of insulin:-
47

48. Protection against gastric degradation:-
48

49. In vivo mucosal adhesion and penetration of the nanoparticles:-
49

50. In vivo hypoglycemic effects:-
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51. CONCLUSION:-
Results indicated that the acid stability of CS NPs and their ability to
protect the entrapped insulin against gastric degradation were sig-
nificantly improved by formulation with HPMCP. Furthermore, the
proposed NPs showed a higher degree of mucoadhesion and deeper
penetration through the small intestine as compared with CS/TPP
NPs. The in vivo data clearly evidenced the ability of CS/HPMCP
NPs to enhance the peroral delivery of insulin.
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52. SUMMARY:-
The concept of bioadhesion involves the binding of a natural or synthetic ,
bioadhesive polymer to biological substrates such as mucous membranes.
Bioadhesive drug delivery systems have been available since the late 1940s and
have become an important route of delivering drugs.
The earlier applications of bioadhesive formulations mainly involved the oral
cavity and the gastrointestinal tract. These days bioadhesive drug delivery
systems have been developed to target a wider variety of mucosal and epithelial
surfaces, these include the vagina, the skin and the nasal cavity.
In most instances bioadhesive formulations are preferred over the conventional
methods of drug delivery. This is because Bioadhesion allows the retention of
the active drug over the mucosal surface and prolongs the contact time between
the polymer and mucosal surface.
Bioadhesive drug delivery also offers a controlled release of drugs. From a
patient’s point of view this is ideal because the frequency of drug administration
is reduced which in turn improves patient compliance.
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