Bioadhesive drug delivery system

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Bioadhesive drug delivery system

  1. 1. BIOADHESION PRESENTED BY SUNIL BOREDDYSUNIL BOREDDY M.Pharmacy (Pharmaceutics)M.Pharmacy (Pharmaceutics)
  2. 2. CONTENTSCONTENTS 2 What is a Bioadhesive Polymer? Bioadhesion and Drug Absorption Bioadhesive Drug Delivery Systems Types of Bioadhesive Formulations Targets for Bioadhesive Formulations Summary
  3. 3. What is a bioadhesive polymer?What is a bioadhesive polymer? 3 Definition History Examples
  4. 4. Definition of a Bioadhesive PolymerDefinition of a Bioadhesive Polymer 4 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.
  5. 5. Mucosal membranesMucosal membranes 5 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.
  6. 6. HistoryHistory 6 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
  7. 7. Examples of polymersExamples of polymers 7 Bioadhesive polymers come from both natural and synthetic sources, some common examples are highlighted below:  Acacia gumAcacia 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 acidAlginic 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.
  8. 8. More examples 8  Hydroxypropyl methylcellulose (HPMC)Hydroxypropyl methylcellulose (HPMC) –– This polymer is included in preparations used to moisten contact lenses and in oral gels.  Sodium hyaluronateSodium 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
  9. 9. Bio adhesion and Drug AbsorptionBio adhesion and Drug Absorption 9 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.
  10. 10. Passive Diffusion 10 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.
  11. 11. Facilitated passive diffusion 11 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.
  12. 12. 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). 12
  13. 13. Pinocytosis 13 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.
  14. 14. Bioadhesion and Drug AbsorptionBioadhesion and Drug Absorption 14 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.
  15. 15. Bioadhesive Drug DeliveryBioadhesive Drug Delivery SystemsSystems 15 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
  16. 16. Bioadhesive Drug Delivery SystemsBioadhesive Drug Delivery Systems 16 Step 1Step 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 polymerThe image below shows swelling of a polymer
  17. 17. Bioadhesive Drug Delivery SystemsBioadhesive Drug Delivery Systems 17 Step 2Step 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
  18. 18. Bioadhesive Drug delivery SystemsBioadhesive Drug delivery Systems 18 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. MechanismsMechanisms of bioadhesionof bioadhesion Step 3Step 3 ► ◄
  19. 19. Characteristics of Bioadhesive polymers 19 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 bondingHydrogen 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 weightHigh molecular weight –– Polymers with a high molecular weight are desirable because they provide more available bonding sites.  Surface tensionsSurface tensions –– Surface tensions are needed to spread the bioadhesive polymer into the mucosal layer epithelial surface.
  20. 20. Types of Bioadhesive Formulations 20 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.
  21. 21. Types of Bioadhesive FormulationsTypes of Bioadhesive Formulations 21 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. 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.
  22. 22. Types of Bioadhesive Formulations 22 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.
  23. 23. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 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 bioadhesiveTable 1 : Sites to which bioadhesive formulations are targetedformulations are targeted 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 23
  24. 24. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 24 1.1.The eyeThe 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.
  25. 25. Some conditions of the eye 25  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.
  26. 26. Ocular Bioadhesive Formulations 26 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
  27. 27. Ocular Bioadhesive Formulations 27  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
  28. 28. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 28 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.
  29. 29. Nasal Bioadhesive Formulations 29 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 PRODUCTSEXAMPLES 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.
  30. 30. Nasal Bioadhesive Formulations 30  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 andcarboxymethyl 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.
  31. 31. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 31 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.
  32. 32. Common conditions affecting the oral cavity 32  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 albicansCandida 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: 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.
  33. 33. Oral Bioadhesive Formulations 33 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 AcaciaAcacia which helps prolong the effect of the drug in the oral cavity. For treatment to be successful each pellet or lozenge must be allowed to slowly dissolve in the mouth, close to the ulcer.
  34. 34. Oral Bioadhesive Formulations 34  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
  35. 35. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 35 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).
  36. 36. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 36 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.
  37. 37. Targets for Bioadhesive Formulations 37 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
  38. 38. Topical Bioadhesive Formulations 38 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.
  39. 39. Topical Bioadhesive Formulations 39 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 acidpolyacrylic acid which holds the patch firmly on the skin surface.
  40. 40. Targets for Bioadhesive FormulationsTargets for Bioadhesive Formulations 40 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 mucosaHistology of the vaginal mucosa
  41. 41. Common conditions affecting the vagina 41 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 TrichomonasTrichomonas vaginalis,vaginalis, dietary deficiency or poor hygiene.
  42. 42. Common conditions affecting the vagina 42  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.
  43. 43. Vaginal bioadhesive formulations 43  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.
  44. 44. 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 44
  45. 45. Targets for Bioadhesive Formulations 45 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.
  46. 46. Rectal Bioadhesive Formulations 46 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.
  47. 47. Summary 47 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.
  48. 48. THANK YOU

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