Bioadhesive drug delivery system

BIOADHESION

PRESENTED BY SUNIL BOREDDYSUNIL BOREDDY

M.Pharmacy (Pharmaceutics) M.Pharmacy (Pharmaceutics)

CONTENTSCONTENTS

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What is a Bioadhesive Polymer?Bioadhesion and Drug AbsorptionBioadhesive Drug Delivery System

sTypes of Bioadhesive Formulation

sTargets for Bioadhesive Formulati

onsSummary

What is a bioadhesive What is a bioadhesive polymer?polymer?

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Definition

History

Examples

Definition of a Bioadhesive Polymer Definition of a Bioadhesive Polymer

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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 membranes. 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.

Mucosal membranesMucosal membranes

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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.

HistoryHistory

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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

Examples of polymersExamples of polymers

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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®.

CarbomersCarbomers 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.

More examples

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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

Bio adhesion and Drug AbsorptionBio adhesion and Drug Absorption

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Drug absorption is the process by which a drug leaves its site of administration and

enters the general circulation. A drug has to cross several cell membranes before

reaching its target tissue or organ.

These membranes act as barriers which control the transport of drugs and other

molecules across cells. The general structure of a cell/plasma membrane consists

of a matrix of proteins surrounded by a phospholipid bilayer.

Drugs may cross a cell membrane by passive diffusion, facilitated passive diffusion,

active transport or pinocytosis. Drug absorption is determined by physicochemical

properties of drugs, their formulations (e.g. tablet,capsule,solution) and routes of

administration such as oral, parenteral or rectal.

Passive Diffusion

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Diffusion is the tendency of molecules to spread into an available space. In theprocess of passive diffusion the transport of molecules across cell membranesdepends very much on the concentration of the molecule.

Most drug molecules are transported across membranes by diffusion from a regionof high concentration (eg.Gastrointestinal fluids) to one of a lower concentrationsuch as blood.

Since cell membranes are lipid in nature, lipidsoluble drugs are able to diffuse across themembrane more rapidly than non-lipid solubledrugs. Small molecules are also ableto penetrate the membrane more rapidly thanlarger ones.

Facilitated passive diffusion

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This is when molecules are transported across membranes and into cells with the

help of carrier proteins. These proteins only interact with certain molecules and

therefore exhibit specificity.

The process of carrier-mediated transport depends on the availability of carriers, this means that at a particular point during transport the carrier will become saturated.

An example of this type of diffusion is thetransport of glucose from blood.

Active TransportActive Transport

Active transport is the movement

of molecules and ions against

their concentration gradients,

from lower to higher

concentrations. This form of

transport requires an input of

energy from cells which is

obtained from ATP (Adenosine

Triphosphate).

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Pinocytosis

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Pinocytosis (a form of endocytosis) allows a cell to engulf large molecules and fluid that may be present in the extracellular region. The cell membrane folds inwards, encloses the fluid or particle to be transported and then fuses to form a vesicle.

The vesicle detaches from themembrane and moves to theinterior of the cell. Pinocytosisplays a role in the transport ofprotein drugs.

Bioadhesion and Drug Bioadhesion and Drug AbsorptionAbsorption

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The adhesion of bioadhesive drugs to mucosal membranes leads to an

increase in the concentration of the drug at its site of action. This means

that a greater amount of drug is available at the specific target site to

cause the desired therapeutic effect.

The concept of using bioadhesive polymers in drug delivery systems is

therefore quite important because it enhances the absorption of drugs.

Bioadhesive Drug Delivery Bioadhesive Drug Delivery SystemsSystems

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In bioadhesive drug delivery systems, the term bioadhesionbioadhesion is used to describe the

bonding or adhesion between a synthetic or natural polymer and soft tissues such

as epithelial cells. The term mucoadhesionmucoadhesion is used to describe adhesion interactions

between polymers and mucus or mucosal surfaces.

Mechanisms of bioadhesionMechanisms of bioadhesion

The mechanisms responsible in the formation of bioadhesive bonds are not fully

known, however most research has described bioadhesive bond formation as 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


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Step 1Step 1The wetting and swelling step occurs when the polymer spreads over the

surface ofthe biological substrate or mucosal membrane in order to develop an

intimatecontact with the substrate. This can be readily achieved for example by

placing abioadhesive 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 thesurface tension and forces that exist at the site of adsorption or contact.

Swelling ofpolymers occur because the components within the polymers have an affinity

forwater. The image below shows swelling of a polymer The image below shows swelling of a polymer


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Step 2Step 2The surface of mucosal membranes are composed of high molecular

weightpolymers known as glycoproteins. In step 2 of the bioadhesive bond

formation, thebioadhesive polymer chains and the mucosal polymer chains

intermingle andentangle to form semi permeable adhesive bonds. The strength of

these bondsdepends on the degree of penetration between the two polymer

groups. In order toform strong adhesive bonds, one polymer group must be soluble in

the other andboth polymer types must be of similar chemical structure.

The interpenetration of polymer The interpenetration of polymer chainschains

Bioadhesive polymer chains

Mucus polymer chains

Bioadhesive Drug delivery Bioadhesive Drug delivery SystemsSystems

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Step 3Step 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 van der

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 Mechanisms of bioadhesion of bioadhesion

Step 3Step 3

► ◄

Characteristics of Bioadhesive polymers

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In order for polymers to adhere to mucosal surfaces or epithelial cell they must

ideally possess certain characteristics: FlexibilityFlexibility- - The flexibility of bioadhesive polymers is important because it

controls the extent of the interpenetration between the polymers and mucosal/epithelial surfaces.

HydrophilicityHydrophilicity – Polymers that are hydrophilic in nature are able to form strong

adhesive bonds with mucosal membranes because the mucus layer contains large amounts of water.

Hydrogen bonding 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 groups are vital in large quantities.

High molecular weight High molecular weight – – Polymers with a high molecular weight are desirable because they provide more available bonding sites.

Surface tensions Surface tensions – – Surface tensions are needed to spread the bioadhesive polymer into the mucosal layer epithelial surface.

Types of Bioadhesive Formulations

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1.Solid Bioadhesive Formulations1.Solid Bioadhesive Formulations: Examples of such formulations are givenbelow.Tablets :Tablets : Dry formulations such as tablets are able to form strong interactions

withmucosal surfaces by attracting water from the mucosal surface. An example isBuccastem® 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 shownthat bioadhesive lozenges are able to release drugs in a controlled manner by prolonging the drug release.

Types of Bioadhesive FormulationsTypes of Bioadhesive Formulations

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2. Semi-solid bioadhesive Formulations2. Semi-solid bioadhesive Formulations

Gels :Gels :Bioadhesive polymers that are able to form gels include polyacrylic acidpolyacrylic acid 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. Anadvantage of gels is that they are able to form a very close contact with

mucosalmembranes 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 withthe membrane and are able to deliver an accurate dose of drug to the site ofabsorption. An example of a bioadhesive film is Zilactin® which is used in thetreatment of cold sores and mouth ulcers.

Types of Bioadhesive Formulations

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3.Liquid Bioadhesive Formulations3.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.

Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations

Bioadhesive or mucoadhesiveformulations have been targeted tovarious anatomical locations to aid

drugdelivery and absorption. Thesestructures possess mucous

membraneswhich protect the cell from damage.Drug delivery to each anatomical

regionis discussed below.

Table 1 : Sites to which Table 1 : Sites to which bioadhesive formulations are bioadhesive formulations are targetedtargeted

Body siteBody site SystemsSystems

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

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1.1.The eyeThe eyeThe eye is one of the most important and complex organs of the body,

because ofits complicated anatomy many things can go wrong with the eye.

Topical drugdelivery systems to the eye can be very difficult to achieve because the

eye hasseveral protective mechanisms in place to get rid of foreign substances. A brief anatomy of the eyeA brief anatomy of the eyeAn effective ocular drug delivery system mustbe easy to use, comfortable to the patientand maintain substantial concentrations ofthe drug in the eye to produce therapeuticeffects.

Some conditions of the eye

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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.

Ocular Bioadhesive Formulations

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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

Ocular Bioadhesive Formulations

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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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2. The Nasal Cavity2. The Nasal CavityThe nasal cavity is the air passage behind the nose. This is the source of

themoisture which is added to air during the breathing process. The nasal

cavity has acomplex structure and can become inflamed during conditions such as the

commoncold, 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 mucociliary clearanceclearance

affects the retention and therefore the effects of the drugs in the nose. Mucociliary clearance transports mucus from the cellslining the nose and protects the respiratory tract fromdamage caused by inhaled substances includingdirt particles and medicines.

Nasal Bioadhesive Formulations

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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.

Nasal Bioadhesive Formulations

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BeconaseBeconase® ® Nasal spray is used to treat nasal inflammation and nasal allergies associated with hayfever. It contains the active ingredient Beclometasone dipropionate and the bioadhesive polymers carboxymethyl cellulose and microcrystalline carboxymethyl cellulose and microcrystalline cellulose. 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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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.

Common conditions affecting the oral cavity

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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.

Oral Bioadhesive Formulations

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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.

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.

Oral Bioadhesive Formulations

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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


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3a.The Buccal Mucosa3a.The Buccal MucosaThe 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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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 longas 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.

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Targets for Bioadhesive Formulations

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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 Cross section of

the skinthe skin

Topical Bioadhesive Formulations

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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

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.

Topical Bioadhesive Formulations

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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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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 squamousstratified squamous

epitheliumepithelium with an underlying layer of connective tissue (lamina proprialamina propria) .

Histology of the vaginal Histology of the vaginal mucosamucosa

Common conditions affecting the vagina

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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.

Common conditions affecting the vagina

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Bacterial vaginosis: Bacterial vaginosis: The causal organism often implicated in C. C. albicansalbicans

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.

Vaginal bioadhesive formulations

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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.

Vaginal bioadhesive formulations

Table 2: Examples of vaginal products

ProductProduct Function of ProductFunction of Product Bioadhesive 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

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Targets for Bioadhesive Formulations

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6.The Rectum6.The Rectum

The rectum is the terminal or end portion of thegastrointestinal tract. It is an important routeof administration for drugs that have severe gastrointestinal side effects. This route is alsosuitable for patients who cannot take medicinesvia the oral route such as unconscious patientsand infants.

The drugs absorbed from the rectum can escapebreakdown by hepatic enzymes. For this reasonmucoadhesive suppositories have been developedfor the local treatment of diseases such as haemorrhoidsand rectal cancer.

Rectal Bioadhesive Formulations

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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 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.

Summary

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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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