Bioadhesive Polymers

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Bioadhesive Polymers

• By Sheila Aidoo Click here to
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Introduction
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• This CAL Package has been developed to give
  Pharmaceutical science students an introduction
  to bioadhesive polymers.
• The Package also includes information on
  different examples of bioadhesive polymers and
  their application in drug delivery systems.

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? ? Main Menu

• What is a Bioadhesive Polymer?
• Bioadhesion and Drug Absorption
• Bioadhesive Drug Delivery Systems
• Types of Bioadhesive Formulations
• Targets for Bioadhesive Formulations
• Summary
• Glossary
• Useful links
• Quiz

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What is a bioadhesive polymer?
? ?

• Definition
• History
• Examples

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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.

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Mucosal 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.

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History
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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 below

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Examples of polymers
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• Bioadhesive polymers come from both natural and
  synthetic sources,
• some common examples are highlighted below
• 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 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 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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More examples
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• Hydroxypropyl methylcellulose (HPMC) This
  polymer is included in preparations used to
  moisten contact lenses and in oral gels.
• 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
• - pectin
• - polyvinylalcohol (PVA)
• - polyvinylpyrrolidone (PVP)
• - tragacanth

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Bioadhesion 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.

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Passive Diffusion
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• Diffusion is the tendency of molecules to spread
  into an available space. In the
• process of passive diffusion the transport of
  molecules across cell membranes
• depends very much on the concentration of the
  molecule.
• Most drug molecules are transported across
  membranes by diffusion from a region
• of high concentration (eg.Gastrointestinal
  fluids) to one of a lower concentration
• such as blood.
• Since cell membranes are lipid in nature, lipid
• soluble drugs are able to diffuse across the
• membrane more rapidly than non-lipid soluble
• drugs. Small molecules are also able
• to penetrate the membrane more rapidly than
• larger ones.

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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 the
• transport of glucose from blood.

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Active Transport
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• 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 the
• membrane and moves to the
• interior of the cell. Pinocytosis
• plays a role in the transport of
• protein drugs.

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Bioadhesion and Drug Absorption
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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.

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Bioadhesive Drug Delivery Systems
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• In bioadhesive drug delivery systems, the term
  bioadhesion is used to describe the
• bonding or adhesion between a synthetic or
  natural polymer and soft tissues such
• as epithelial cells. The term mucoadhesion is
  used to describe adhesion interactions
• between polymers and mucus or mucosal surfaces.
• Mechanisms 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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Bioadhesive Drug Delivery Systems
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• 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.
• 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.
• The image below
  shows swelling of a polymer

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Bioadhesive Drug Delivery Systems
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• 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 chains
• Bioadhesive
• polymer chains
• Mucus
• polymer chains

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Bioadhesive Drug delivery Systems
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• 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 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 of bioadhesion
• 
  
  Step 3
• 
  
  

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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
• Flexibility- The flexibility of bioadhesive
  polymers is important because it controls the
  extent of the interpenetration between the
  polymers and mucosal/epithelial surfaces.
• Hydrophilicity 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 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 Polymers with a high
  molecular weight are desirable because they
  provide more available bonding sites.
• Surface tensions Surface tensions are needed to
  spread the bioadhesive polymer into the mucosal
  layer epithelial surface.

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Types of Bioadhesive Formulations
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• 1.Solid Bioadhesive Formulations Examples of
  such formulations are given
• below.
• 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 vertigo. It is
• administered to the buccal mucosa (inside of the
  cheeks).
• 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 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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Types of Bioadhesive Formulations
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• 2. Semi-solid bioadhesive Formulations
• Gels Bioadhesive polymers that are able to form
  gels include polyacrylic 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. 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 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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Types of Bioadhesive Formulations
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• 3.Liquid Bioadhesive Formulations
• 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 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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Targets for Bioadhesive Formulations
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• 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.
• Table 1 Sites to which bioadhesive formulations
  are targeted

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Targets for Bioadhesive Formulations
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• 1.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 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.
• 
  

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Some conditions of the eye
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• 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 this occurs when people dont 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 This disorder is characterised by
  pressure in the eyeballs and causes excessive
  amounts of aqueous 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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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
• mucin 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 PRODUCTS
• Hypotears and 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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Ocular Bioadhesive Formulations
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• GelTears 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 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 ACID

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Targets for Bioadhesive Formulations
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• 2. 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 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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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 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
• Rhinocort 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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Nasal Bioadhesive Formulations
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• Beconase 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 cellulose.
• 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 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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Targets for Bioadhesive Formulations
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• 3. 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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Common conditions affecting the
oral cavity
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• 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 This is an infection caused by the
  fungus Candida albicans 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 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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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 PRODUCTS
• Corlan 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 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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Oral Bioadhesive Formulations
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• Bonjela 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 oral gel contains the antifungal agent
  Miconazole and is used to treat oral thrush. It
  also contains an adhesive agent known as
  pregelatinised 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 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) which helps retain the gel inside
  the oral cavity.

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Targets for Bioadhesive Formulations
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• 3a.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 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 Products
• Buccastem Is a drug used in the treatment of
  nausea, vomiting and vertigo. It contains the
  bioadhesive agents Polyvinylpyrrolidone and
  Xanthan gum.
• Suscard Is a buccal tablet used in the
  treatment of angina. It contains the bioadhesive
  agent Hydroxypropyl methylcellulose (HPMC).

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Targets for Bioadhesive Formulations
? ?

• 3b. The sublingual mucosa
• The sublingual mucosa surrounds the sublingual
  gland which is a mucin-producing
• salivary 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 (GTN) aerosol spray
• and tablet which is administered under the tongue
  for the prophylactic treatment of
• angina.

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Targets for Bioadhesive Formulations
? ?

• 4.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 skin
• 
  

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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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Topical Bioadhesive Formulations
? ?

• Examples of Products
• Voltarol 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 carbomer which aids the
  absorption of the active drug by spreading it
  into the affected area.
• 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 piroxicam but the gel also
  contains two bioadhesive agents to increase its
  retention at the absorption site. These agents
  are Carbopol 980 and hydroxyethyl cellulose.
• 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 gum and
  polyacrylic acid which holds the patch firmly on
  the skin surface.

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Targets for Bioadhesive Formulations
? ?

• 5. 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 squamous
• epithelium with an underlying layer of connective
  tissue (lamina propria) .
• Histology of the vaginal mucosa
  The female reproductive System

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Common conditions affecting the vagina

? ?

• The epithelium of the vagina contains glycogen,
  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 infections
• 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,
  dietary deficiency or poor hygiene.

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Common conditions affecting the vagina
? ?

• Bacterial vaginosis The causal organism often
  implicated in C. albicans
• this infection is Gardnerella 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) Is a common yeast infection
  caused
• by the organism Candida albicans. The signs
  and symptoms
• of thrush are a white cheesy discharge that
  itches and irritates
• the vagina.
  
  T. vaginalis
• Trichomoniasis Is a sexually - transmitted
  infection caused
• by the organism Trichomonas vaginalis. The
  symptoms in
• women include vaginal itching as well as a
  frothy, foul-smelling,
• greenish-yellow discharge.

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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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Vaginal bioadhesive formulations
? ?

• Table 2 Examples of vaginal
• products

47
Targets for Bioadhesive Formulations
? ?

• 6.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.

48
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 PRODUCTS
• Anacal Is a rectal ointment used to relieve the
  symptoms associated with haemorrhoids. It
  contains the bioadhesive agent polyethylene high
  polymer 1500.
• Germoloids Is a rectal ointment used to relief
  the pain, swelling, itchiness and irritation
  associated with haemorrhoids. It contains the
  polymer propylene glycol.
• Preparation H Suppositories help shrink the
  haemorrhoidal tissue which is swollen by
  irritation. It contains the polymer polyethylene
  glycol.

49
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
• patients point of view this is ideal because the
  frequency of drug administration
• is reduced which in turn improves patient
  compliance.

50
Glossary
? ?

• Angina (angina pectoris) A sense of pain in the
  centre of the chest which may
• spread to the jaws and arms. It may occur as a
  result of an increase in the demand
• of oxygen by the heart.
• Basal Layer Is also known as the basement
  membrane. It is a thin delicate
• membrane that lies at the base of an epithelium
  and contains connective tissue.
• Cellulose Is a complex carbohydrate consisting
  of linked glucose units. It is the
• primary constituent of plant cell walls.
• Epithelium The tissue that covers the external
  surface of the body and lines the
• inside of the body cavities.
• Glycogen Glycogen is a carbohydrate consisting
  of branched chains of glucose
• units. It is stored in the liver and muscles.

51
Glossary
? ?

• Haemorrhoids Enlargement of the blood-filled
  cushions in the wall of the
• anus. The anal tissue becomes itchy and painful.
• Oestrogen A hormone that controls female sexual
  development as well as
• promoting the function of the female sex organs.
• Progesterone A steroid hormone responsible for
  preparing the inner lining of the
• uterus for pregnancy.
• Prophylactic An agent that prevents the
  development of a condition or disease.
• Spermicidal contraceptive An agent that kills
  mature male sex cells.
• Stratified squamous Refers to a type of
  epithelium which consists of one or more
• cell layers. The cells are flat and scale-like in
  nature.
• Vertigo A sensation of dizziness or a confused,
  disorientated state of mind.

52
Useful Links
? ?

• www.answers.com/
• www.bnf.org
• http//www.drugdeliverytech.com
• http//www.drugdeliverytech.com/cgi-bin/articles.c
  gi?idArticle159
• www.medicines.org.uk
• http//www.netdoctor.co.uk/

53
Quiz
? ?

• Question 1.
• Which one of the following is NOT a natural
  polymer?
• a) Acacia gum
• b) Tragacanth
• c) Carbomer
• d) Alginic Acid

54
? ?

• Question 2.
• What is the primary constituent of mucus?
• a) Water
• b) Glycoproteins
• c) Inorganic salts
• d) Fats

55
? ?

• Question 3.
• The structure on the right represents
• a )Cellulose
• b) Pectin
• c) Tragacanth
• d) Polyacrylic acid

56
? ?

• Question 4.
• The only types of bonds formed between polymer
  chains and
• biological substrates are hydrogen bonds and Van
  der Waals forces.
• a) True
• b) False

57
? ?

• Question 5.
• Which of the following best describes the order
  of bioadhesion?
• a) Spreading, bond formation and penetration
• b) Bond formation, swelling and absorption
• c) Swelling, interpenetration and bond formation
• d) Swelling, interpenetration and absorption

58
? ?

• Question 6.
• The biological polymer sodium hyaluronate is used
  in ocular drug delivery
• systems and contains repeating units of
• a) Glucosamine
• b) Glucose
• c) Glycogen
• d) Glucagon

59
? ?

• Question 7.
• The buccal mucosa is the most permeable route of
  drug delivery within the
• oral cavity.
• a) True
• b) False

60
? ?

• Question 8.
• Zidoval contains the bioadhesive agent carbomer
  and is used to treat
• a) Candidiasis
• b) Vaginitis
• c) Bacterial vaginosis
• d) Vaginal atrophy

61
? ?

• Question 9.
• Which of the following gels contain
  pregelatinised potato starch as its
• bioadhesive agent?
• a) Feldene
• b) Corsodyl
• c) Pilogel
• d) Daktarin

62
? ?

• Question 10.
• Mucociliary clearance in the nose is increased by
  the presence of bioadhesive
• polymers.
• a) True
• b) False

63
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END OF QUIZ