The document discusses bioadhesion and mucoadhesion. It defines bioadhesion as materials adhering to biological tissues for extended periods via interfacial forces. Mucoadhesion specifically refers to adhesion between materials and mucosal surfaces. Mucoadhesive drug delivery systems can prolong drug release at application sites, improving therapeutic outcomes. Ideal mucoadhesive polymers rapidly adhere to mucosal layers without interfering with drug release, are biodegradable and non-toxic, and enhance drug penetration at delivery sites. The mechanisms of bioadhesion involve wetting, swelling, interpenetration and entanglement of polymer chains followed by secondary bonding formations. Key factors influencing bioadhesion are discussed.

1. By,
 Dr. Shreeraj Shah
 Associate Professor,
 Dept. of Pharmaceutical
Technology
 L.J. Institute of Pharmacy,
Ahmedabad

2.  Bioadhesion may be defined as the state in which two materials, at least
one of which is biological in nature, are held together for extended
periods of time by interfacial forces.
 The rationale being that the formulation will be ‘held’ on a biological
surface for localized drug delivery.
 The API will be released close to the site of action with a consequent
enhancement of bioavailability.
 It is a phenomenon of interfacial molecular attractive forces amongst the
surfaces of the biological substrate and the natural or synthetic polymers,
which allows the polymer to adhere to the biological surface for an
extended period of time
 For the purpose of drug delivery system
Drug carrier system  adhere to biological tissue  increase
concentration gradient at the absorption site  increase the
bioavailability.
 Also used for
• local target to the mucosal surface
• reduce the side effect

3.  Mucoadhesion is commonly defined as the
adhesion between two materials, at least one of
which is a mucosal surface.
 Mucoadhesive dosage forms may be
designed to enable prolonged retention at the
site of application, providing a controlled rate of
drug release for improved therapeutic outcome.

4.  Bioadhesion is defined as an ability of a material
to adhere to a biological tissue for an extended
period of time.
 In the case of polymer attached to the mucin
layer of a mucosal tissue, the term “mucoadhesion”
is used.

5. The ideal characteristics of a Bio/Mucoadhesive
approach include:
The rapid adherence to the mucosal layer without any
change in the physical property of the delivery matrix,
minimum interference to the release of the active
agent,
biodegradable without producing any toxic
byproducts,
 enhance the penetration of the active agent (if the
active agent is meant to be absorbed from the delivery
site)

6.  The formulation stays longer at the delivery site improving API bioavailability using lower API
concentrations for disease treatment
 The use of specific bioadhesive molecules allows for possible targeting of particular sites or
tissues
 Increased residence time combined with controlled API release may lead to lower
administration frequency
 The avoidance of first-pass metabolism
 Dose-related side effects may be reduced due to API localization at the disease site
 These dosage forms facilitate intimate contact of the formulation with the underlying absorption
surface. This allows modification of tissue permeability for absorption of macromolecules
,such as peptides and proteins. Inclusion of penetration enhancers such as Sodium glycocholate,
Sodium taurocholate and L-lysophosphotidyl choline and protease inhibitors in the
mucoadhesive dosage forms resulted in better absorption of peptides and proteins.

7.  Medications administered orally do not enter the blood stream
immediately after passage through the buccal mucosa. Instead they
have to be swallowed and then have to pass through a portion of the
GIT before being absorbed. So the action is not very rapid in the GIT
as compared when the drug is administered through buccal route.
 Certain drugs when ingested undergo drug destruction, there are
several drugs which are potentially in this category. Many drugs
affect liver metabolism and also cause destruction via first pass
metabolism of other drugs.
 Oral ingestions results in more exposure of a drug to the GI tract.
One of the side effects of many antibiotics is the destruction of
normal GI flora resulting in diarrhea and overgrowth with dangerous
organisms such as C. difficile.
 The absorption of mucoadhesive drugs is adversely affected by the
presence of food. Tetracyclines, in particular, complicates the
administration of this class of antibiotics via the oral route.

8.  Mucoadhesive Inner layers called mucosa Inner
epithelial Cell lining Covered with viscoelastic
fluid.
 It is secreted by Goblet cells lining the epithelia or
by special exocrine glands with mucus cells
composed of water and mucin (an anionic
polyelectrolyte).
 Other components include proteins, lipids,
electrolytes and mucopolysaccharides
 Thickness varies from ≈40–50 μm to ≈300 μm

9. Regions in mucus layer

10.  General composition of mucus :
Water……………………….95%
Glycoprotiens and lipids….0.5-5%
Mineral salts……………….1%
Free proteins………………0.5-1%
 These units contain an average of about 8-10
monosaccharide residues of five different types.
They are:
a) L-fucose
b) D-galactose
c) N-acetyl-D-glucosamine
d) N-acetyl-D-galactosamine
e) Sialic acid

11.  Complex-high molecular weight macromolecule consisting
of a polypeptide (protein) backbone to which carbohydrate
side chains are attached.
Generic structure of mucin monomer

12. Mucus forms flexible, threadlike strands that are internally
cross linked by disulphide bond.
Disulphide bond present in mucus
The mucus layer which covers the epithelial surface has
various roles:
• Protective
• Barrier
• Adhesion
• Lubrication

13. MUCUS MEMBRANE STRUCTURE STRUCTURE OF MUCIN

14.  The mechanisms responsible in the formation of
mucoadhesive bonds are not fully known, however
most research has described mucoadhesive bond
formation as a three step process.
Step 1 : Wetting and swelling of polymer (the
contact stage)
Step 2 : Interpenetration between the polymer
chains and the mucosal membrane
Step 3 : Formation of chemical bonds between the
entangled chains (both known as
consolidation stage)

15. 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 mucoadhesive formulation such as a
tablet or paste within the oral cavity or vagina. Swelling of
polymers occur because the components within the
polymers have an affinity for water.

16. Step 2
The surface of mucosal membranes are composed of high
molecular weight polymers known as glycoproteins. In step 2 of
the mucoadhesive bond formation, the mucoadhesive 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.

17. 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
mucoadhesive formulations in which strong adhesions between
polymers are formed.

18.  The Theories include :-
(1) The electronic theory.
(2) The wetting theory.
(3) The adsorption theory.
(4) The diffusion theory.
(5)The Fracture theory
(6) The mechanical theory.
(7) The cohesive theory.
 The phenomena of bioadhesion occurs by a complex
mechanism. There are seven theories have been
proposed till date

19. 1) The Electronic theory
 Electronic theory is based on the premise that both
mucoadhesive and biological materials possess opposing
electrical charges. Thus, when both 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) The 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 found by using measuring techniques such
as the 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

21. 3) The Adsorption theory
 According to the 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. For example, hydrogen bonds are the
prevalent interfacial forces in polymers containing
carboxyl groups.
 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

22. 4) The 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.
 According to the literature, the depth of
interpenetration required to produce an efficient
bioadhesive bond lies in the range 0.2-0.5 μm

23. 5) The Fracture theory
 This theory attempts to relate the difficulty of
separation of two surfaces after adhesion
 It analyzes the force required to separate two surfaces
after adhesion
Adhesion Strength = (E ԑ/L )1/2
E =Young’s modulus of elasticity
ԑ = Fracture energy
L = Critical crack length when two surfaces are
separated

24. 6) The mechanical theory
 Mechanical theory considers 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
7) The cohesive theory
 It proposes that the phenomena of bioadhesion are
mainly due to the intermolecular interactions amongst
like-molecules.

25.  Polymer related factors:
Molecular weight
Concentration of active polymer
Flexibility of polymer chains
Hydrogen bonding capacity
Presence of functional group
Spatial conformation
Cross linking density
Charge on polymer
Hydration
Hydrophilicity
 Environment related factors :
pH of polymer – substrate interface
Applied strength
Initial contact time
Swelling
 Physiological factors:
mucin trun over

26. POLYMER RELATED FACTORS:-
1) Molecular weight
 Bioadhesion is maximum at certain molecular weight.
 Low molecular weight  interpenetration is more
 High molecular weight  entanglement is more
 Bioadhesive force of polymers is increase up to molecular
weight 10000, beyond which there is no further gain.
2) Concentration of active polymer
 In high concentration coiled molecules of polymer become
solvent poor and chains available for bioadhesion are less.
 In low concentration bioadhesion of polymer also
decreases.

27. 3) Degree of hydration
 Depending on the degree of hydration adhesive properties
are different. It is maximum at a certain degree of hydration.
 High degree of hydration  formation of slippery, non-
adhesive mucilage due to large amount of water leads to loss
of adhesiveness.
4) Charge on polymer
 Mucosal surface is negatively charged. So positively
charged polymer might facilitate the mucoadhesive process.
 Chitosan have bioadhesion due to electrostatic attraction
between positively charged D- glucosamine residue of
chitosan and negatively charged sialic acid residues.

28. 5) Presence of functional group
 Due to immobilization of thiol groups on polymers like chitosan &
polyacrylic acid their permeation enhancement, enzyme inhibitory &
mucoadhesive properties are improved.
 The immobilization of thiol groups on microparticles improves
mucoadhesive properties.
6) Spatial conformation
 Besides molecular weight or chain length, spatial conformation of a polymer
is also important. Despite a high molecular weight of 19,50,0000 for
dextrans, they have adhesive strength similar to that of polyethylene glycol
(PEG), with a molecular weight of 2,00,000. The helical conformation of
dextran may shield many adhesively active groups, primarily responsible for
adhesion, unlike PEG polymers, which have a linear conformation.

29. ENVIRONMENT RELATED FACTORS:-
(1) pH
• pH influences the charge on the surface of both mucus and
the polymers.
• Mucus will have a different charge density depending on
the pH because of the difference in the dissociation of the
functional groups on the carbohydrate moiety and amino
acids of the polypeptide backbone.
• Polyacrylic acid polymers  degree of hydration increase
upto pH 4 to 5  slightly increase at pH 6 to 7 
decreasing at more alkaline pH.
(2) Applied strength
• To place a solid bioadhesive system, it is necessary to apply
a defined strength. The adhesion strength increases with the
applied strength or with the duration of its application, up to
an optimum level.

30. (3) Initial contact time
 The initial contact time between the mucoadhesives and the
mucus layer determines the extent of swelling and the
interpenetration of the polymer chains.
 The mucoadhesive strength increases as the initial contact
time increases.
(4) Swelling
 Interpenetration of chains is easier when polymer chains are
disentangled and free of interactions.
 When swelling is too great, a decrease in the bioadhesion
occurs, such phenomena must not occur too early, in order
to lead to a sufficient time for action of the bioadhesive
system.

31. PHYSIOLOGICAL FACTORS:-
(1) Mucin turnover
 The natural turnover of the mucin molecules from the
mucus layer is important for at least two reasons-
 The mucin turn over is expected to limit the residence
time of mucoadhesive dosage form on the mucus layer.
 Mucin turnover results in substantial amount of soluble
mucin molecules. These mucin molecules interact with
mucoadhesive dosage form before they have a chance to
interact with the mucus layer.
(2) Disease states
 The physiological properties of the mucus are known to
change during disease conditions such as the common cold,
gastric ulcers etc. The exact structural changes taking place
in mucus under these conditions are not yet clearly
understood.

32.  They are water soluble and water insoluble
polymers which are swellable networks joined by
cross linking agents.
 Characteristic of ideal polymer
 Degradation products should be non toxic and non
absorbable from GIT
 Good spreadability, wetting, swelling, solubility
and biodegradability properties
 Optimum molecular weight
 Non irritant to mucous membrane
 Form a strong non covalent bond with mucin
epithelial cell surfaces

33.  Adhere quickly to moist tissue
 Allow easy incorporation of the drug
 Not decompose on storage or during shelf life of dosage
form
 Should possess site specificity
 Cost effective
 Should approved by regulatory authorities

34. According to source
Natural and modified natural Synthetic
Agaros Carbopol
Chitosan Polycarbophil
Gelatin Polyacrylic acid
Hyaluronic acid Polyacrylates
Carrageenan Methacrylic acid
Pectin Poly Vinyl Alcohol
Sodium alginate Poly Vinyl Pyrollidine
Carboxy Methyl Cellulose Ethylhexaacrylate
Thiolated CMC Thiolated polymer, etc.
Sodium CMC
HEC
HPC
HPMC
Methylhydroxyethylcellulose, etc.

35. According to water solubility
Water soluble Water insoluble
CMC, Thiolated CMC, Sodium Carbopol,Polycarbophil,
CMC, HEC, HPC,HPMC, MC, Polyacrylic acid, Polyacrylates
HPMC,PVA,PVP, etc. Methacrylic acid, PEG, etc.
According to charge
Cationic and Anionic Uncharged
Aminodextran, Chitosan, Hydroxyethylated starch,
Chitosan-EDTA, Carbopol HPC, PEG
Polycarbophil, Sodium alginate, PVA, PVP, etc.
Pectin, Sodium CMC, CMC, etc.

36. Route/site Bioadhesive formulation
Oral cavity (Buccal Tablet, Patch, Gel, Ointment,
and Sublingual) Chewing gum, Hollow fibers
Nasal Gel, Microspheres, Dry powders
Ocular Insert, gel
Gastro intestinal Gel, Tablet, Microspheres, Capsule,
Hollow fibers
Skin/Transdermal Patch, Liposomes
Vaginal Gel, Microspheres, Tablet
Rectal Gel

37.  Bioadhesive tablets are immobilized drug delivery
systems
 Formulated as monolithic, partially coated or
multilayered matrices
 Formulation ingredients
1) API 6) Sweetening agent
2) Mucoadhesive polymer 7) Flavoring agent
3) Permeation enhancer 8) Coloring agent
4) Diluent 9) Buffering agent
5) Lubricant 10) Backing layer
polymers

38. Designs of bioadhesive tablets

39.  Small surface of contact with mucosa
 Lack of physical flexibility
 Difficult to obtain high release rate, which is
required for some drugs
 The extent and frequency may cause irritation to
mucosa

40. 1)Weight variation
2) Thickness
3) Hardness
4) Friability
5) Drug content
6) Surface pH
7) In vitro drug release
8) In vitro drug permeation
9) Swelling study
10) Measurement of residence time / retention time
11) Adhesive strength determination

41. Measurement of residence time / retention time
 Provides quantitative information on mucoadhesive
properties.
 The GI transit time of many mucoadhesives have been
examined using radioisotopes .
e.g. 51Cr and the time dependent distribution of the
radioactivity in the GIT is measured.
 Esophageal bioadhesive property
porcine oesophageal tissue is used.
 tissue is washed at a rate of 1ml/min
with simulate saliva flow.
 1.5 mL of formulation was mixed with ~0.2 MBq Tc99m as a
radioactive substance. Eluate is collected upto 30 min.
fig : In-vitro apparatus used to measure the residence
time to perticular tissue.
41

42. Measurement of mucoadhesive strength
Three different types of stress, tensile, shear and peel stress
are measured
A) Tensile strength

43. B) Shear and Peel strength
C) Thumb test
The adhesiveness is qualitatively measured by the
difficulty of pulling the thumb from the adhesive as a
function of the pressure and the contact time. It provides
useful information on mucoadhesive potential

45. Dissolution of Buccal tablet:-
fig : Mumtaz and Chang model for the dissolution of
the buccal tablet.
 From the inlet dissolution medium is poured and from
outlet it is collected and assayed.
45

46.  Gels includes bioadhesive gels and in situ forming gels
 Bioadhesive gels
 These gels highly viscous semisolids prepared by using
mucoadhesive polymers
 Formulated for various sites like buccal, nasal, vaginal,
rectal,etc

47.  Formulation ingredients of bioadhesive gel
1) Active pharmaceutical ingredient
2) Mucoadhesive polymer
3) Permeation enhancer
4) Preservative
5) Solvent

48.  In situ gels are in solution form and formed gels upon
administration to particular site due to phase transition in
environment of that site
 Gel formation is due to various mechanisms includes,
 Thermal change
 pH change
 change in electrolyte composition
 combination of any 2 mechanisms

49. Thermo sensitive gel forming system
Thermo sensitive polymer systems are formed from
aqueous polymer solutions with temperature changes
Thermo sensitive polymers are copolymers of N-
isopropylacrylamide (PNiPAAM), polaxamer, etc.
pH sensitive gel forming system
pH sensitive gel forming systems, which swell or shrink
in response to changes in the pH
Carbopol (polyacrylic acid) is mostly used as pH
sensitive polymer

50.  Ion sensitive gel forming system
 Ion sensitive gel forming system is new type of gel, in
which solution of polymer containing drug triggered to
gel form when contact with specific ion at specific site
 Ion sensitive polymer includes sodium alginate, gellan
gum, xyloglucan, carrageenan
 In situ gels formulate for various sites including nasal,
ophthalmic, oral, vaginal, rectal

51. 1) Drug content
2) Viscosity
3) pH
4) In vitro drug release
5)Adhesion properties: Adhesive strength is measured
as described in tablets and the other methods are,
A)Membrane viscosity
 The interaction between polymers and cell
membranes was examined by labeling the cell
membranes with fluorescent probes

52.  The lipid bilayer and proteins of cell
membranes were labeled with pyrene and
fluorescein isothiocyanate
 The fluorescence spectrum of pyrene and the
fluorescence depolarization of fluorescein
isothiocyanate were used to examine the
change in membrane viscosity after
interaction with polymer
 It was assumed in this study that affinity of
polymers to cell membranes is linearly
related to the increase in membrane viscosity

53. B) Electrical conductance
 The adhesion of orabase, carbopol, guar gum, and
methyl cellulose to artificial biomembrane in artificial
saliva was studied by using a modified rotational
viscometer capable of measuring electrical conductance
 In presence of adhesive material the conductance was
comparatively low. As the adhesive was removed the
value increased to final corresponding to conductance
of saliva, which indicate the absence of adhesion

54.  Patches are designed for buccal delivery and transdermal
delivery of drugs
 Buccal patches
 Designed either for unidirectional release or bidirectional
release
 Use of impermeable backing layer will maximize the drug
concentration gradient and prolong adhesion because the
system is protected from saliva
 Typically size of such polymeric patches would be 1-3 cm 2 but
may have dimensions as large as 10-15 cm2 depending on the
site of administration

55.  Patch contains mucoadhesive polymer and supportive
material
Matrix system Reservoir system

56.  Formulation ingredients of Buccal patch
1) API
2) Mucoadhesive polymer
3) Supporting material
4) Plasticizer
 Evaluation of Buccal patch
1) Thickness uniformity
2) Folding endurance
3) Uniformity of weight
4) Drug content uniformity
5) Swelling study
6) Surface pH
7) In vitro release study
8) Adhesive strength

57.  Transdermal patches
 Transdermal patch is a medicated adhesive placed on
the skin to deliver a specific dose of medication
through the skin and into bloodstream
 Formulation is same as buccal patches
 Evaluation of Transdermal patches
1) Thickness uniformity
2) Moisture content
3) Uniformity of weight
4) Drug content uniformity
5) Flatness study
6) Surface pH
7) In vitro release study
8) Adhesive strength

58. Mucoadhesion measurement by Modified balance method

59.  Chewing gums are mobile drug delivery systems
 The main target mucosa for drug absorption is sublingual
mucosa
 Drug release is generally rapid but not as immediate as in case
of fast dissolving tablets
 Commercially available medicated chewing gums are
currently available for pain relief, smoking cessation, travel
illness, and freshening of breath
 Medicated chewing gum offers advantages in comparison to
conventional oral mucosal and oral dosage forms both for (a)
local treatment of mouth diseases and (b) systemic effect after
absorption through the buccal and sublingual mucosa or from
the gastrointestinal tract

60.  Components of chewing gum
Component Concentration (%)
Drug Max. approximately 50
Gum base 20–40
Bulk sweeteners 30-75
Softeners 0-10
Flavoring agents 1-5
Coloring agents ˂1

61.  Manufacturing process of chewing gum
 The most common method comprises mixing the
gum base with the other ingredients in a mixer with
Z formed blades. The gum base can either be added
in a solid form and softened through heating from
the jacket of the mixer or from the frictional heat
generated during the mixing process, or it can be
added in a melted form.
 Chewing gum can also be manufactured by
compression of powders or granulates on a
conventional tablet machine (compression
technique).

62.  The release into saliva and disappears rapidly from the
oral cavity because of involuntary swallowing
 The concentration drug in the oral cavity always tends to
decrease as a result of salivary dilution
 The drug is not protected from the environment found in
oral cavity
 Administration of such dosage form is restricted to short
time periods because the delivery system in the oral
cavity causes disturbance in drinking, eating and speaking

63.  Films are used for buccal bioadhesive drug delivery
 Both degradable and non-degradable forms of films have
been developed
 The major method of polymeric film manufacture is the
solvent evaporation process
 Formulation ingredients
1) API
2) Mucoadhesive polymer
3) Plasticizer

64.  Evaluation of film
1) Weight uniformity
2) Thickness
3) Swelling study
4) folding endurance
5) Drug content uniformity
6) Surface pH
7) In vitro drug release
8) Mucoadhesion study

65.  Solid ophthalmic delivery devices (inserts) are thin disks or
small cylinders made with appropriate polymeric materials
and fitting into the lower or upper conjuctival sac
 Their long persistence in the perocular area can result in a
greater drug bioavailability with respect to liquid and
semisolid formulations
 Mucoadhesive polymers can be profitably used as constituents
of inserts to achieve prolonged contact with the conjuctival
tissue

66.  Alternative approach for chewing gum formulations
 The design of micro porous hollow fiber of polysulphone
intended for the delivery of histerelin, a LHRH agonist was
reported (Burnside et al.)
 This fiber is intended to be placed in the buccal cavity for oral
mucosal drug delivery
 The fiber may also prepare for periodontal application

67.  Multiparticulate system includes microspheres, liposomes and
nanoparticles
Microspheres
 Bioadhesive microspheres include micro particles and
microcapsules(size 1–1000µm in diameter)
 They have the potential to be used for targeted and controlled
release drug delivery; but coupling of bioadhesive properties to
microspheres has additional advantages,
 Efficient absorption and enhanced bioavailability of the drugs
due to a high surface to volume ratio
 A much more intimate contact with the mucus layer
 Specific targeting of drugs to the absorption site

68.  Bioadhesive microspheres can be tailored to adhere to any
mucosal tissue including those found in eye, nasal cavity,
urinary and gastrointestinal tract, thus offering the possibilities
of localized as well as systemic controlled release of drugs
 Their formulation contains API and mucoadhesive polymer
 Liposomes
 Liposomes are coated with mucoadhesive polymers and
remain for longer period of time and improved the drug
therapy
 Ocular route is widely used for mucoadhesive liposomal
preparation
 Nanoparticles
 Nanoparticles prepared for mucoadhesive drug delivery by
either consisting entirely of a bioadhesive polymer or having
an outer coating of it

69.  Evaluation of multiparticulate system
1) Drug entrapment efficiency
2) Particle size analysis
3) In vitro release study
4) Mucoadhesion study
 Mucoadhesion study
In microspheres adhesion number is determined
 The adhesion number (Na) is,
Na = (N/No)*100
Where, No = total no. of applied particles
N = no. of particles attached to the substrate
 Two methods for measurement
A)Falling liquid film method
B) Mucin gold staining

70. A)Falling liquid film method
The adhesion of particles to this surface is measured by
passing the particle suspension over the surface and
by comparing the fraction of particles adhered to the
tissue

71. B) Mucin gold staining
 In this technique, colloid gold particles, which are red
in solution, are stabilized by mucin molecules
 The interaction between mucin and adhesive particles is
monitored by appearance of red color on surface.

72. EVALUATION OF BDDS
 IN VITRO / EX VIVO METHODS
a. Methods based on measurement of tensile strength.
b. Methods based on measurement of shear strength.
OTHER IN VITRO METHODS
c. Adhesion weight method
d. Fluorescent probe method
e. Flow channel method
f. Falling liquid film method
g. Colloidal gold staining method
h. Mechanical spectroscopic method
I. Thumb test
j. Viscometric method
k. Adhesion number

73.  IN VIVO METHODS
a. Use of radio isotopes
b. Use of gamma scintigraphy
In vivo evaluation methods
 In vivo methods used for evaluation are based on
administration of polymers to a laboratory animal and
tracking their transit through the GI system.
 Administration methods include forced oral gavage,
surgical stomach implantation and infusion through a
loop placed in situ in the small intestine. Tracking
generally followed with the help of X-ray studies, radio
opaque markers and radioactive elements etc.
 For e.g. X- ray studies for monitoring GI transit time for
bioadhesive tablet made of BaSO4 and radiolabelled
microspheres and nanoparticles.
73

74.  Ocular (Eye)
 Nasal cavity
 Oral (Buccal and Sublingual)
 Skin/Transdermal
 Gastro-intestinal and Colorectal
(Colon+ Rectum)
 Vaginal

75.  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.
 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.
 Problems associated with eye include conjunctivitis,
Glaucoma and dry eye.

76. Ocular Bioadhesive Formulations
 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.

77.  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.
 The effects of bioadhesive polymers on mucociliary
clearance was examined by Zhou and Donovan
(1996).
 Methylcellulose exhibited the most reduction in
mucociliary clearance whilst Carbopol 934P showed
the least reduction in mucociliary clearance in the rats
used.

78. Bioadhesive formulations for Nasal cavity
 Rhinocort® Nasal spray is a powdered mixture of the steroid
Beclomethasone dipropionate(50μg) and 30mg of Hydroxypropyl
cellulose(HPC).
 Used for patients suffering from nasal allergy.
 The powder sticks to and swells on the cells lining the nose and remains
there for about 6 hrs.
 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.

80.  The oral cavity or the mouth comprises of the cheeks, teeth
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.
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.

81. The Buccal Mucosa
 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).
The sublingual mucosa
 Drugs administered via the sublingual route are formulated
as tablets, powders, solutions or aerosol sprays.
 Examples of sublingual products include Glyceryl
Trinitrate (GTN) aerosol spray and tablet which is
administered under the tongue for the prophylactic
treatment of angina.

82.  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
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

83. Transdermal Bioadhesive formulations
 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.

84.  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.

85. Rectal Bioadhesive Formulations
 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.

86.  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)
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 such as Vaginitis, Bacterial vaginosis, Candidiasis
(Thrush), Trichomoniasis etc..

87. 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.
 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 optimise the spread of the formulation over the
vaginal epithelium.

88.  S-DBMP-T(Slowly Disintegrating
Buccal Mucoadhesive Plain-Tablet)
 BCTS (Buccal Covered-Tablet System)
 VagiSiteTM Bioadhesive Technology

89.  Iga et al. developed this system
 S-DBMP-T are prepared by incorporating a relatively
large amount of hydroxypropylcellulose in a tablet
formulation
 An example of a typical composition is a tablet
composed of 20 mg of drug, 20 mg of
hydroxypropylcellulose, 20 mg of
carboxymethylcellulose (ECG-505, disintegrating
agent), and 60 mg of lactose
 The S-DBMP-T technology was originally developed
for increasing the bioavailability of oxendolone (a
steroidal anti-androgen)

90.  To maintain the tablet shape for as long as possible, Iga
et al. developed a method to restrict disintegration from
the sides of the tablets
 The method involved sandwiching a S-DBMP-T tablet
between two polyethylene sheets. The upper sheet
contained a hole that allowed the tablet to absorb water
and disintegrate only through the hole. The lower sheet
contained adhesives to allow the delivery system to
adhere to the gingiva for a long time.

91.  Developed by KV Pharmaceutical Company, St. Louis,
Missouri, U.S.A.
 The VagiSiteTM technology comprises a high-internal-phase-
ratio, water-in-oil emulsion
 The internal phase of the emulsion acts as the carrier of the
active drug. The drug-laden internal-dispersed phase globules
serve a dual purpose for both the sequestering and the
controlled release of the active agent, butoconazole nitrate
 After introduction of the drug-containing emulsion to a
mucosal surface, in this case the vaginal mucosa, a thin
bioadhesive film of contiguous drug-laden internal-phase
globules forms on the mucosal surface

92.  Rathbone MJ et al., Modified Release Drug Delivery
Technology, Marcel Dekker, Inc., 2002, 349-81, 801-6
 Vyas SP, Khar RK., Controlled Drug Delivery: Concepts and
Advances, Vallabh Prakashan, First Edition: 2002, 257-314
 Methiowitz E et al., Bioadhesive Drug Delivery System,
Marcel Dekker, Inc., 1999, 551-3, 621-31
 Andrews GP et al., Mucoadhesive polymeric platforms for
controlled drug delivery, European Journal of Pharmaceutics
and Biopharmaceutics 71 (2009) 505–18
 Salamat-Miller N et al., The use of mucoadhesive polymers in
buccal drug delivery, Advanced Drug Delivery Reviews 57
(2005) 1666– 91