The document discusses mucosal drug delivery systems that utilize bioadhesive properties for targeted drug administration via various mucosal surfaces. It highlights the advantages such as bypassing first-pass metabolism and enhanced bioavailability, as well as the principles of bioadhesion and the mechanisms involved. Additionally, it addresses formulation considerations for buccal drug delivery, including potential advantages and disadvantages of the approach.

1. Mucosal Drug Delivery System
Presented By:
Pranali M. Palandurkar
University department of
Pharmaceutical Sciences R.
T.M.N.U nagur

2. Contents
 Introduction
 Principle of bioadhesion
 Concept of mucosal delivery system
 Advantages & Disadvantages
 Transmucosal permeability
 Formulation & consideration of buccal drug delivery system
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3. INTRODUCTION
 Delivery of drugs via the absorptive mucosa in various easily accessible body cavities, like
the ocular, nasal, buccal, rectal and vaginal mucosae, has the advantage of bypassing the
hepato-gastrointestinal first-pass elimination associated with oral administration.
 Mucosal membranes can be useful sites with good accessibility for easy application of
drug delivery systems, especially for those with bio(muco)adhesive properties.
 Mucoadhesive drug delivery systems utilize the property of bioadhesion of certain
polymers which become adhesive on hydration and hence can be used for targeting a
drug to a particular region of the body for extended periods of time and can be exploited
for the noninvasive systemic delivery of organic- and peptide-based drugs, with rapid
absorption as well as sustained drug action
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4. PRINCIPLE OF BIOADHESION
There are six classical theories adapted which explain the phenomenon of adhesion.
1.Electronic theory- When both mucoadhesive and biological materials come into contact, they
transfer electrons leading to the building of a double electronic layer at the interface, where the
attractive forces within this electronic double layer determines the mucoadhesive strength.
2.Adsorption theory- The mucoadhesive device adheres to the mucus by secondary chemical
interactions, such as in van der Waals and hydrogen bonds, electrostatic attraction or hydrophobic
interactions. Such forces have been considered the most important in the adhesive interaction
phenomenon because, although they are individually weak, a great number of interactions can result
in an intense global adhesion
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5. 3.Wetting theory-The wetting theory applies to liquid systems which present affinity to the surface in
order to spread over it. This affinity can be measure by contact angle. The general rule states that the
lower the contact angle then the greater the affinity The contact angle should be equal or close to
zero to provide adequate spreadability
The spreadability coefficient, SAB, can be calculated from the difference between the surface
energies γB and γA and the interfacial energy γAB, as indicated in equation
SAB= γB- γA- γAB
The greater the individual surface energy of mucus and device in relation to the interfacial energy, the
greater the adhesion work, WA, i.e. the greater the energy needed to separate the two phases
WA=γA+γB-γAB
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6. 4.Diffusion theory-Diffusion theory describes the interpenetration of both polymer and mucin chains
to a sufficient depth to create a semi-permanent adhesive bond. It is believed that the adhesion force
increases with the degree of penetration of the polymer chains. This penetration rate depends on the
diffusion coefficient, flexibility and nature of the mucoadhesive chains, mobility and contact time. This
interpenetration depth of polymer and mucin chains can be estimated by the following equation
l = (tDb)½
Where, t - contact time
Db -diffusion coefficient of the mucoadhesive material in the mucus.
The adhesion strength for a polymer is reached when the depth of penetration is approximately
equivalent to the polymer chain size.
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7. 5.Fracture theory-It analyses the force required to separate two surfaces after adhesion is
established . The force Sm is frequently calculated in tests of resistance to rupture by the ratio of
the maximal detachment force,Fm and the total surface area A0
Sm=Fm/A0
6.Mechanical theory-This theory consider adhesion to be due to the filling of the irregularities
on a rough surface by a mucoadhesive liquid. Moreover ,such roughness increases the interfacial
area available to interactions thereby aiding dissipating energy and can be considered the most
important phenomenon of the process.
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8. CONCEPT OF BIOADHESION
 Bioadhesion is the state in which two materials ,(at least one of which is biological in nature), are
held together for a extended period of time by interfacial forces.
 The term bioadhesion implies attachment of drug-carrier system of specific biological location. This
biological surface can be epithelial tissue or the biological surface can be epithelial tissue or the
mucous coat on the surface of tissue.
 If adhesive attachment is to mucous coat then phenomenon is referred as mucoadesion.
 These drug delivery system utilize property of bioadhesion of certain water soluble polymers which
become adhesive on hydration and hence can be used for targeting particular sites.
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9.  Mechanisms of Bioadhesion – The mechanism responsible in the formation of bioadhesive
bonds are not fully known ,however most research has described bioadhesive bond formulation
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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10. Mucosal drug delivery offers several advantages over other controlled release systems :
 High drug flux at the absorbing tissue.
 Painless and ease of administration.
 Low enzymatic activity and avoid of first pass metabolism.
 Targeting and localization of the dosage form at a specific site.
 Termination of therapy is possible.
 drugs which are unstable in acidic environment of stomach or destroyed by the alkaline
environment of intestine can be given other mucosal route .
 Drug shows poor bioavailability by oral route can be administered by other mucosal route .
ADVANTAGES
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11.  It follows passive diffusion , and does not require any activation.
 The presence of saliva ensures large amount of water for dissolution of drug unlike in case of
rectal and transdermal route.
 Thin mucin film exist on the surface of oral cavity provides opportunity to retain delivery system
in contact with mucosa for prolonged period of time with the help of mucoadhesive compounds
 The buccal membrane is sufficiently large to allow delivery system to be placed at different
sites on the same membrane for different occasion , if the drug or other excipients cause
reversible damage or irritate mucosa .
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12. DISADVANTAGES
 Over hydration may lead to formulation slippery surface and structural integrity of the formulation
may get disrupted by the swelling and hydration of the bioadhesion polymer.
 Eating and drinking may become restricted
 Drug which irritate mucosa or have a bitter or unpleasant taste or an obnoxious odour cannot be
administered by this route .
 Only drug which are absorbed by passive diffusion can be administered by this route .
 Only small dose drug can be administered .
 In case of ,buccal tablet there is possibility that patient may swallow the tablet.
 Costly drug delivery system.
 Unfortunately , the lack of standardized techniques often leads to unclear result. 12

13. TRANSMUCOSAL PERMEABILITY
 Mucosal routes provide the potential pathways to bypass hepatogastrointestinal first-pass
elimination following oral administration. Transmucosal drug delivery has the potential to
achieve greater systemic bioavailability for orally metabolized drugs, including organic- and
peptide-based pharmaceuticals.
 There are two routes potentially involved in drug permeation across epithelial membranes:
a) Transcellular route
b)Paracellular route
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14. 1)Paracellular route: For hydrophilic compounds
 This compound is difficult to penetrate into the lipophilic cell membrane .
 Intercellular space is preferred route for drug transport
 Drug movement in this route (JH)can be written as
(JH)=DH Є CD
hH
Where Є= fraction of surface area of paracellular route
DH= diffusion coefficient
hH= pathlength of paracellular route
CD=donar side drug concentration
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15. 2)Transcellular route:
For lipophilic compound.
Drug molecule move across both lipophilic cell membrane and hydrophilic cytoplasm as well
as intercellular space.
The permeability of lipophilic compound across the epithelial cell membrane is typically high .
Drug flux is transcellular route (JL) can be expressed as:
JL=(1-Є)DH KP CD
hL
Where , KP =partition coefficient between lipophilic and hydrophilic region
hL= pathlength of transcellular route
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16. Various potential mucosal pathways for systemic delivery of therapeutic agents.
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17. Buccal Delivery: Drugs are delivered through mucosal membrane into systemic circulation by placing
drug in between cheeks and gums.
Classification of Buccal Bioadhesive Dosage Forms
 Buccal Bioadhesive Tablets.
 Buccal Bioadhesive semisolids.
 Buccal Bioadhesive patch and films.
 Buccal Bioadhesive Powders.
Formulation consideration of Buccal drug
delivery system
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18. Advantages of Buccal Drug Delivery System
 The residence time of dosage form at the site of absorption is prolong, hence increases
the bioavailability.
 Rapid onset of action.
 High blood supply and good blood flow rate cause rapid absorption.
 In the acidic medium of git drug is protected from degradation.
 Improved patient compliance.
 Nor painful neither irritations.
Disadvantages of Buccal Drug Delivery System:
 Prolonged contact of the drug possessing ulcerogenic property.
 For the in vitro screening of drugs the oral mucosal delivery is lack of good model. This is the
major drawback of this drug delivery.
 Patient acceptability in terms to taste, irritancy and mouth feel is to be checked.
 As compared to the sublingual membrane the buccal membrane is low permeability.
 Also has smaller surface area.
 The dissolution of drug due to continuous secretion of saliva (0.5-2 l/day).
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19. The basic components of buccal bioadhesive drug delivery system are :
 Drug substance -Drug used for rapid release/prolonged release and for local/systemic effect is a
suitable candidate for buccal delivery
 Bioadhesive polymers-Bioadhesive polymers play a major role in buccoadesive drug delivery
systems of drugs. Polymers are also used in matrix devices in which the drug is embedded in the
polymer matrix, which controls the duration of release of drugs.
 Backing membrane-Backing membrane plays a major role in the attachment of bioadhesive
devices to the mucus membrane.
 Penetration enhancers- To increases the permeation rate of the membrane of co-administrated
drug penetration enhancer are added. Without causing toxicity and damaging the membrane they
improve the bioavailability of drugs that have poor membrane penetration
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20. Components Examples
Bioadhesive polymers Agarose, chitosan, gelatin, Hyaluronic acid,
Poly(acrylic acid)-based polymers, Hydroxyethyl
starch ,PVA, PVP, scleroglucan
Backing membrane Carbopol, Magnesium separate, HPMC, HPC,
CMC, Polycarbophil
Penetration enhancers Sodium lauryl, Cetylpyridinium chloride,
Poloxamer, Sodium gylcodeoxycholate, Oleic
acid, Ceprylic acid, Trimethyl chitosan, EDTA
,sodium citrate.
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21. Marketed Formulation
Product Company Bioadhesive agent Dosage Form
Buccastem Reckitt Benckiser PVP, Xanthum Gum Buccal Tablet
Corlan Pellets Celtech Acacia gum Oromucosal Pellets
Suscard Forest HPMC Buccal Tablet
Orabase Convatech Pectin ,Gelatin Oral Paste
Corsodyl Gel Glaxosmith Kline HPMC Oromucosal Gel
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