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BIO ADHESIVE DRUG DELIVERY SYSTEM
PUNDARIKA.S.S.PRASAD.K
Y9MPH410
|| SEMESTER, | M.PHARMACY11
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Bioadhesive
Bioadhesive polymer
Characteristics of bioadhesive polymers
Mechanism of bioadhesion
Types of Bioadhesive formulations
Targets for Bioadhesive Formulations
Evaluation of bioadhesive drug delivery systems
Conclusion
References
CONTENTS
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BIOADHESION
Bioadhesion is the process that describes the
adhesion of a polymer to a biological substrate.
Adhesion is defined as the bond produced by
contact between pressure sensitive adhesive and
a substrate.
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Polymer
Bioadhesive polymer
Biological glues
Bioadhesive polymer
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Mucosal membranes
These are moist membranes that line passageways
and structures in the body that lead to the outsideenvironment such as the mouth, respiratory tract,
gastrointestinal tract, nose and vagina. They
secrete a viscous fluid known as mucus.
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Characteristics Of Bioadhesive Polymers
Molecular weight, chain length and cross-linking
density:
Polymers with a high molecular weight
(above 100,000) are desirable because they providemore available bonding sites.
- chen and cyr,1970
Flexibility:Controls the extent of the interpenetration
between the polymers and mucosal/epithelial surfaces
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Hydrophilicity ::To form strong adhesive bonds with
mucosal membranes because the mucus layer contains large amounts of water.
Surface tension :Surface tension is needed to spread the
bioadhesive polymer into the mucosal layer epithelial surface.
Charges and ionization :Polyanionic polymers are preferred
over polycationic and neutral polymers.
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Polyanions with carboxyl groups are better
candidates than those with sulfates.
Hydrogen bonding :Hydrogen bonding between the
entangled polymer chains forms strong adhesive
bonds, therefore the presence of hydrogen bond ±
forming groups such as OH and COOH groupsare vital in large quantities.
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Polymers are ideally non toxic and should be non
absorbable from GIT.
Polymers should be nonirritant to mucous
membrane, and form a bonding with mucin-epithelial
cell surfaces.
The polymers must not decompose on storage or
during shelf life of a dosage form.
The cost of the polymers should not be high so that
the prepared dosage form remains competitive.
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Examples of bioadhesive polymers
Natural polymers : Synthetic polymers :
- tragacanth - cellulose derivatives
- acacia - poly acrylic acid
- sodium alginate - carbomers- lecithin - poly carbophil
- gelatin - poly vinyl alcohol
- chitosan - poly hydroxy ethyl
methyl acrylate
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Mechanism of Bioadhesion
Wetting and swelling of polymer
Interpenetration between polymer chain and
mucosal membrane
Formation of chemical bonds between the
entangled chains
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Drug release from
muco adhesive drug
delivery system
BIOADHESION
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Theories of Bioadhesion
o Wetting theory
o Diff usion theory
o Electronic theory
o Adsorption theory
o Fract ure theory
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Non specific interactions
Bioadhesion can be obtained by the
building of either non-specific interactions with the
mucosal surface, which are driven by the physicochemical properties of the particles and the
surfaces
Specific interactionswhen a ligand attached to the particle
is used for the recognition and attachment to a
specific site at the mucosal surface.1414
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Types of Bioadhesive formulations
Solid Bioadhesive FormulationsTabletsInsertsLozenges
Semi-solid bioadhesive FormulationsGelsFilms
Liquid Bioadhesive Formulations Viscous liquidsGel forming liquids
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Mucoadhesive tablet adhered to
buccal mucosa
Solid bioadhesive formulation
Buccastem tablet
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Gels and Films
Crinone gel
Zilactin-B film
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Liquid bioadhesive formulations
Artificial tears to treat dry eyes1818
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Targets for Bioadhesive Formulations
Bioadhesive formulations have been targeted
to various anatomical locations to aid drugdelivery and absorption. The structure possess
mucous membranes which protect the cell
from damage.
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BODY SITE SYSTEMS
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 2020
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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.
Ocular bioadhesive drug delivery
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Hypo tears®
Carbopol
Sno Tears®Sno Tears®
pilogel® pilogel®
Examples of ocular bioadhesive formulations
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Gel tears and visco tears :
Liquid gel eye drops are used for dry eye
conditions and contain carbomer 980(poly acrylicacid).carbomers lubricate the eye by clinging to the
surface of the eye. This can reduce the frequency of
application into the eye.
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Drugs such as antihistamines and steroids areadministered as nasal drops or nasal sprays to treat
conditions affecting the nose.
However nasal mucociliary clearance affects the
retention and therefore the effects of the drugs in
the nose.
One of the most important feature of nasal route
is that it avoids the first-pass metabolism.
Nasal bioadhesive drug delivery
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Examples of Nasal bioadhesive formulations
Nasacort®
Rhinocort®
Beconase®
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For the first time investigation done by Nagai et.alon peptides and proteins was used is dry powder
formulation containing muco adhesive polymer.
Microspheres are another way of prolonging theresidence time in the nasal cavity.
The addition of muco adhesive excipients
(chitosan) results in clearance rate.
Using mixture of drugs, PEG400 and carbopol 931
they obtain a relatively high and sustained drug
plasma concentration. 2626
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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
Oral bioadhesive drug delivery
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Corlan®
Bonjela®
Daktarin®
Corsodyl®
Examples of Oral bioadhesive formulations
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The buccal mucosa refers to the inner lining of the lips and cheeks. The epithelium of the buccalmucosa is about 40-50 cells thick.
The epithelial cells become flatter as they movefrom the basal layers to the superficial layers
Buccastem - nausea and vomiting
Polyvinylpyrrolidone
Xanthan gum
Suscard - angina
HPMC
Delivery through Buccal mucosa
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The buccal route avoid first-pass metabolism. This
region consist of non keratinized epithelium , results
in more permeable to skin.
Drugs with short biological half life, require a
sustained effect and exhibiting poor permeability.
These is good way to deliver via., oral cavity.
Nagai et.al formulated high viscous gel ± carbopol
and hydroxy propyl cellulose ±for ointment dosage
of maintaned on tissue upto 8 hrs.3131
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The sublingual mucosa surrounds the sublingualgland which is a mucin-producing salivary glandlocated underneath the tongue.
This mucosa is relatively permeable and gives arapid absorption of many drugs due to its excellent blood supply.
This route is appropriate for many drugs as longas the drug is able to go into solution with saliva inthe mouth.
Example: Glyceryl Trinitrate (GTN) aerosol spray
and tablet -prophylactic treatment of angina.
Delivery through sublingual mucosa
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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
Bioadhesive products targeted to the skin areformulated into different dosage forms which
include liquids, powders and semi-solids such as
ointments and transdermal patches.
Topical bioadhesive drug delivery
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Voltarol® Emulgel
Feldene®
Evorel®
Examples of Topical bioadhesive formulations
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The intravaginal route has been used todeliver contraceptives as well as anti-infectiveagents such as antif ungal drugs to exert a localeffect .
Localised application of vaginal formulationsenables the spread of these formulations overthe target area, which allows an effective
therapy.
Bioadhesive polymers are incorporated intovaginal formulations to aid the adhering of thedosage form to its target site.
Vaginal Bioadhesive drug delivery
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Among the polymers, poly acrylic acid and
hydroxy propyl methyl cellulose as an ideal
excipients in muco adhesive strength.
Robinson et.al reported on system of treatment
using a gel containing muco adhesive poly
carbophil that remained on vaginal tissue for 3-4
days and hence served as a platform for delivery of drug such as Progesterone.
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Bioadhesive polymers are incorporated intorectal suppositories to prolong the retention of the active drug in the rect um.
Prolonged retention in the rect um increasesthe chances of reaching a therapeutic out come
Rectal Bioadhesive drug delivery
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Anacal®
Germoloids®
Preparation H®
Examples of Rectal bioadhesive formulations
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Hydrogels administered rectally have proven
to be used for drug delivery.
Leede et.al. proposed Hydrogels using
hydroxy ethyl methacrylate cross linked with
ethylene glycol dimethacrylate and including anti
pyrene and theophylline as model drugs providedrate controlled drug delivery.
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Name andform
Drug Mucoadhesivepolymers
Applicationsite
Attach tablet Tri amcinoloneacetonide
HPC , carbopol934
Oral cavity
Susadrin tablet Nitroglycerin Synchron(modified HPMC)
Buccal cavity
Buccastem tablet Pro chlorperazinemaleate
Xanthan gum Buccal cavity
Orabase gel - Sodium CMC,gelatin in
polyethylene oilbase.
Oral cavity
Rhinocort powder
Beclomethasone HPC Nasal cavity
Replens gel - Poly acrylic acid Vaginal cavity.
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Evaluation of bioadhesive drug delivery systems
The morphological evaluation of drug
carrier(especially micro carriers) include ±
SEM,TEM and FTIR.
Invitro release studies carried out by using-
dissolution apparatus, diffusion method and
incubation of formulation in the medium.
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The prepared tablets were attached to freshly
excised intestinal mucosa, which has been spanned
on a stain less steel cylinder(diameter-4.4cm, height-
5.1cm, apparatus usp xxII). There after, the cylinder was placed in dissolution
apparatus according to the USP containing 100 mM
TBS pH 6.8 at 37.5 0.5 ºc. The fully immersed
cylinder was agitated with 250 rpm. The detachment, disintegration and erosion of test
tablets were observed and recorded with in time
period of 10 hours.
Muco adhesive studies
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Conclusion
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 nasalcavity.
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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S.P.Vyas and Roop K. Khar-Controlled drug
delivery ±-vallabh prakashan publications -2006
edition ± pg no 257-310.
PHARMATIMES ± vol.38-no.4-april 2006-pg
no. 25-27
Chen J.L. and cyr G.N (1970) adhesion in
biological systems academic press,london,163.
http://www.drugdeliverytech.com/cgi-
bin/articles.cgi?idArticle=159
REFERENCES
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