Mucoadhesive drug delivery system has gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the bio- logical system
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Mucosal Drug Delivery System
1. -Guided by Dr. Varsha Pokharkar.
Vice-Principal
HOD (Pharmaceutics)
- Represented by Swati Sen.
Roll no.-12
F.Y. M.Pharm Sem-II
(Pharmaceutics)
2. Contents > Introduction
> Mechanism of Mucoadhesion
> Theories of Mucoadhesion
> Factors affecting Mucoadhesion
> Mucoadhesive polymers
> Routes of administration
> Mucoadhesive dosage form
> Characterization methods
> Case study
> References
3. What is Bioadhesion / Mucoadhesion ?
The term bioadhesion implies attachment of a drug carrier system
to a specified biological location.
The biological surface can be epithelial tissue or it can be the mucus
coat on the surface of a tissue.
The adhesive attachment of the drug carrier system to a mucous
coat/ layer, the phenomenon is referred to as mucoadhesion.
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.
4. Mucoadhesive drug delivery system interact with the
mucus layer covering the mucosal epithelial surface, &
mucin molecules & increase the residence time of the
dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of
controlled delivery system.
Combining the mucoadhesive with the enzyme
inhibitory and enhances penetration and also improves
patient compliance.
5. Advantages Targeting & localization of the dosage form at a specific site.
High drug flux at the absorbing tissue.
Excellent accessibility.
Painless administration.
Low enzymatic activity & avoid of first pass metabolism.
Disadvantages If MDDS are adhere too tightly it exert too much force to remove the formulation after
use, otherwise the mucosa could be injured.
Medications administered orally do not enter the blood stream.
Lack of standardized techniques often lead to unclear results.
Costly drug delivery system
Some patient suffers unpleasant feeling.
Prolongation of residence time.
Ulcer causing drugs may precipitate ulcerogenic effect due to
increase in residence time.
6. What is mucous?
• Mucoadhesive inner layer called mucosa is the inner epithelial cell
lining covered with viscoelastic fluid.
• Composed of water and mucin.
• Thickness varies from 40μm to 300 μm
General composition of mucosa
• Water………………………………95%
• Glycoprotein and lipids…………0.5-5%
• Mineral salts……………………….1%
• Free proteins………………………0.5-1%
7.
8. Mechanisms of Mucoadhesion
The mechanism of mucoadhesion is generally divided in two steps:
A) The Contact Stage and
B) The Consolidation Stage.
9. Mechanism Of Mucoadhesion
• The mechanism if responsible for the formation of the
mucoadhesive bond.
• Three steps are involved:
Step 1: wetting and swelling of the polymer(contact stage)
Step 2: interpenetration between the polymer chains and
the mucosal membrane.
Step 3: formation of bonds between the entangled chains
(both known as consolidation stage)
10. • The mechanisms governing mucoadhesion are also
determined by the intrinsic properties of the formulation
and by the environment in which it is applied.
Intrinsic factors of the polymer are related to its
• molecular weight,
• concentration and
• chain flexibility.
12. Theories of Mucoadhesion
• Electronic theory
Electronic theory is based on the premise that both mucoadhesive and
biological materials possess opposing electrical charges.
• 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.
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.
13. • Wetting theory
The wetting theory applies to liquid systems which
presents the 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
contact angle 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 as
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 phase
14. It is believed that the adhesion force increases with the degree of penetration
of the polymer chains.
The penetration rate depends on the diffusion coefficient, flexibility and
nature of the mucoadhesive chains, mobility and contact time.
• Diffusion interlocking theory
Diffusion theory describes the interpenetration of both polymer and mucin
chains to a sufficient depth to create a semi-permanent adhesive bond.
According to the literature, the depth of interpenetration required to produce
an efficient bioadhesive bond lies in the range 0.2-0.5 µm.
This interpenetration depth of polymer and mucin chains can be estimated by
the equation:
(3)
𝑤ℎ𝑒𝑟𝑒, 𝑡 𝑖𝑠 𝑡ℎ𝑒 𝑐𝑜𝑛𝑡𝑎𝑐𝑡 𝑡𝑖𝑚𝑒,
𝐷 𝑏 𝑖𝑠 𝑡ℎ𝑒 𝑑𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛
𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑡.
15. • Fracture theory
The “fracture theory” relates the force for polymer detachment from the
mucus to the strength of their adhesive bond.
The fracture is found to be greater when the polymer network strands are
longer or the degree of cross-linking within the system is reduced.
This theory allows the determination of fracture strength (σ) following the
separation of two surfaces via its relationship to Young's modulus of
elasticity (E), the fracture energy (ε) and the critical crack length(L) through
following equation
(4)
16. Factors Affecting Mucoadhesion
A. Polymer related factors
a. Molecular weight
b. Chain length
c. Spatial arrangement
d. Flexibility
e. Hydration of polymer
f. Hydrogen bonding
g. Polymer concentration
B. Environmental factors
a. pH
b. Applied Strength
c. Contact Time
d. Swelling
C. Physiological factors
a. Mucin Turnover
b. Disease State
19. Oral mucoadhesive drug delivery system
• Oral route is most preferred route for the delivery of any drug.
In oral drug delivery, mucoadhesion is provided by the formation of
• non-covalent bonds such as hydrogen bonds and ionic interactions
or
• physical adhesion between the mucus layer and mucoadhesive
polymers.
Gingival
Sublingual
Buccal
Drug
delivery
20. Advantages
• The buccal cavity provides highly vascular mucous
membrane site for the administration of drugs.
• Drug degradation in stomach, first-pass metabolism is
avoided and therapeutic drug levels of drug can be
achieved rapidly.
• avoidance of pain and discomfort related with the
injections as well as the removal of potential infections
caused by the use of needles.
21. Components and the structural feature of
oral mucosa
• Oral cavity is the area of mouth delineated by the lips, cheeks, hard palate,
soft palate and floor of mouth.
A. Epithelium:
Oral
mucosa
epithelium
basement
membrane
• The epithelium consists stratified squamous epithelium.
• It serves as a protective covering from the tissue and barrier to the entry of
foreign materials.
• The stratified squamous epithelia consists of a mitotically active basal cell
layer, represent the major absorption sites in the oral cavity.
22. • Unlike the skin, which has a complete turnover period of 30 days, the oral
mucosa has a turnover time in the range of 3-8 days.
B. Basement membrane and
connective tissues:
• This layer is a continous layer of
extracellular materials and
forms a boundary between the
basal layer and the connective
tissues.
• This basal complex anchors the
epithelium to the connective
tissue and supplements the
barrier function of the
superficial layers of the
epithelium to prevent some
large molecules from passing
through the oral mucosa.
• The bulk of connective tissue
consists of a collagen fibre
network, the organization of
which determines mechanical
23. stability, resistance, to deformation and extendibilty of the
tissue.
• Oral mucoadhesive dosage forms readily consists of
three features as follows:
1. They are readily localized in the oral cavity to improve
and enhance the bioavailability
2. They facilitate intimate contact of the formulation with
the underlying adsorption surface
3. They allow the modification of the tissue permeability
for absorption of macromolecules
Eg: peptide protein
They also prolong the residence time of the dosage form
to permit once or twice-a-day dosing.
24. i. Buccal drug delivery
The buccal epithelium is composed of approximately 40-50 cell
layers, while sublingual layer consist of fewer cell layers. In humans,
dogs, and rabbits, the buccal mucosa measures 500-800 pm in
thickness.
The drug administration through the mucosal membrane lining of
the cheeks (buccal mucosa).
The buccal region offers an attractive route of administration for the
controlled systemic drug delivery.
Buccal ,mucosa has an expanse of smooth muscle and relatively
immobile mucosa which makes it more desirable region for
retentive system.
Mucoadhesive dosage
forms in the buccal cavity
include :adhesive tablets,
adhesive gels, adhesive
patches, and adhesive
ointments.
25. Advantages Contact with the digestive fluid is avoided
Well known for its good accessibility to the membrane that lines the
oral cavity
Disadvantages Saliva is continously secreted into oral cavity diluting the drug
resulting low drug concerntration.
Taste, irirtancy, allergy, and adverse properties like discolouration or
erosion of teeth may limit the drug use.
Patient can terminate the delivery in case of emergencies
The novel buccal dosage formulations exhibit better patient
compliance
Conventional type of bucaal drug delivery system did not allow to
eat, drink, or talk(in some cases)
26. ii. Sublingual drug delivery
The sublingual region generally shows
the higher drug permeability than the
buccal region.
The substance is fastly absorbed via the blood vessels below the the
tongue rather than the digestive tract.
This route is been used for delivery of drugs having rapid onset of
action.
Eg. Nitroglycerine.
The latest developments have been applied to the treatment of
angina pectoris, cancer, and in the cure of smoking.
27. Advantages
• Fast onset of action is achieved
• Avoids first pass metabolism
• Low dosage give high efficacy as
hepatic first pass metabolism is
avoided.
• Large contact surface of the oral
cavity contributes to rapid
absorption
Disadvantages
• The sublingual administration
of drugs interferes with
drinking, eating and talking.
• Unconcious patient cannot
administer sublinguly
28. iii. Gingival drug delivery
The gingival mucosa is being exploited for the
application of sustained release mucoadhesive
dosage forms.
Buccal tablets adhere to the gingival
mucosa for a period of six hours, without
interffereing with the nomal functioning of the mouth.
This dosage form could provide a viable alternative to intra muscular
administration.
30. Nasal Drug Delivery
The nasal route is an ideal alternative to
the parentrals for administering drugs
intended for systemic effect, in view of the rich
vascularity of the nasal membranes and the ease
of intranasal administration.
Besides avoidance of hepatic first-pass elimination.
Controlled release can achieved also be after nasal administration.
A number of polymers used in nasal mucoadhesion have been
thoroughly tested in humans for other application and most have
already GRAS (Generally Regarded as Safe) status.
31. Ocular Drug Delivery
Various strategies were developed to enhance the bioavailability of
ophthalmic drugs by prolonging the contact time between the
formulations and the corneal/conjunctival epithelium.
Viscous semi-solid preparations, like gels and ointments, provide a
sustained contact with the eye, but they induce sticky sensation,
blurred vision, irritation and reflex blinking due to discomfort
Mucoadhesive concept is now implemented as new approach to
optimise the ocular dosage form.
32. Mucoadhesive polymers action
carbopol 934P
& carbopol 1342-
prolongation of precorneal
residence time of liposomes
polyalkylcyanoacrylate
(PACA)
& poly-ε-caprolactone
(PECL) nanoparticles
improve the corneal
penetration of hydrophilic
and lipophilic drugs
In particular, the effectiveness of of liposomes in ocular drug depends
on many factors but chiefly on the liposomal surface charge, which
determines the precorneal vesicle retention.
It was concluded that positively charged liposomes add to the corneal
penetration of drugs as compared to neutral or negatively charged
liposomes.
33. Vaginal and Rectal Drug Delivery
Vaginal Bioadhesive preparations have been developed
as a new type of controlled-release form for the
treatment of both topical and systemic diseases.
+ The greatest advantage of such dosage forms is the
possibility of maintaining them in the vagina for extended
periods of time including daytime and nighttime, thereby
enabling lower dosing frequencies.
Drugs administered rectally as a suppository
34. Different types of mucoadhesive dosage forms Delivery route
Delivery
routes
Dosage form
tablets ointments gel patch film
Buccal Theophyllin
e, multiple
polymers
Benzyl
nicotinate,m
ultiple
polymers,
Benzydamine,
chitosan
derivative,
Miconazole,
PVA/PVP
Fentanyl,
PVP
Nasal N/A Mupirocin,
glycerin
ester
Insulin,starch Insulin,
chitosan/PEG
Chlorpromaz
ine,chitosan/
pectin
Occular Diclofenac,
poly(acrylic)
acid
Sulphadicra
mide,
multiple
polymers
Puerarin,poloxa
mer/carbopol
Ciprofloxacin,
PVA/CMC
Fluorescein,
HPMC
Vaginal Metronidazo
le, chitosan
Terameproc
ol, white
petroleum
Amphotericin,
pluronic
ALA,
PMVE/MA
SDS, multiple
polymers
Rectal Ramosetron,
carbopol
Zinc oxide,
petroleum
Quinine, HPMC N/A Theophylline,
pHEMA
35. Mucoadhesive dosage form:
Semisolids > gels and ointment
> films
>patches
Solids >tablets
>matrix tablets
>bioadhesive microparticles
Liquids >suspensions
>gel forming liquids
Mucoadhesivedosage
forms
36. • Tablets
Generally they are prepared by direct compression, but wet
granulation techniques can also be used.
To get sustained release and more mucoadhesion, tablets can be
coated with water impermeable materials.
Example: ethyl-cellulose and hydrogenated castor oil.
Multilayered tablets might be designed by successively adding and
compressing the ingredients layer by layer.
Sometimes mucoadhesive microspheres are also formulated, prior
to direct compression into tablets so as to get enhanced action and
prolonged drug release.
Adhesive tablets: Unlike conventional tablets, bioadhesive tablets
allow drinking and speaking without major discomfort.
Eg: Triamcinolone acetonide has been formulated as a bioadhesive
tablet for the treatment of aphthous stomatitis.
37. • Matrix tablets: (a) monolithic
(b) two layered tablets
• In monolithic tablets:- mixture of drug + swelling
bioadhesive polymer bidirectional release and outer side
coated with impermeable hydrophobic substance.
• In two layered matrix tablets:- comprises of an inner
layer based on bioadhesive polymer and an outer non-
bioadhesive layer containing the drug for a bi-directional
release but only local action.
• In case of systemic outer layer is inert and acts as a protective
layer.
38. • Patches:
Buccal patch is a non-dissolving thin matrix modified release
dosage form composed of one or more polymer films or layers
containing drug and/or other excipients.
The patch contains a mucoadhesive polymer layer which bonds to
the oral mucosa, gingiva, or teeth for control drug release in oral
mucosa, oral cavity or both.
Mucoadhesive buccal patches can be prepared either by solvent
casting or direct milling.
The size of the patches can vary from 1 to 15𝑐𝑚2. The smaller the
size, the more convenient and comfortable are the patches. Patches
may be
An impermeable backing
layer may also be applied
to control the direction of
drug release, prevent drug loss,
and minimize deformation and
disintegration of the device.
39. • In solvent casting method,
• In direct milling method,
casting the solution of the
drug and polymers onto
backing layer sheet
Patches are
prepared
Solvent is
allowed to
evaporate
formulation
constituents are
homogeneously
mixed
compressed (for
required thickness )
patches
(required)size and
shape then cut or
punched out.
40. • Films:
films are the recently formulated
dosage form for buccal administration
which are preferred over mucoadhesive
buccal tablets in terms of flexibility and
comfort and can also avoid the comparatively short residence time of
oral gels on the mucosa, which are easily removed by saliva.
Besides, the buccal films also take care of the wound surface in local
delivery for oral infections, thus reduce pain and do effective
treatment.
They are generally prepared by a solvent casting method
drug and polymers are
dissolved in a casting
solvent
mixture solution is
casted into films,
dried,
laminated
with a backing layer.
41. • Gels and ointments:
Gels and ointments are semisolid dosage forms with the
advantages of uncomplicated dispersion throughout the
oral mucosa. But, dosing from semisolid dosage forms
not much as exact as from tablets, patches, or films.
Mucoadhesive formulations are used to defeat the poor
retention time of gels.
Bioadhesive polymers,
e.g. poloxamer 407,
sodium carboxy methylcellulose,
carbopol, hyaluronic acid, and xanthan gum, go through a
phase transition from a liquid to a semisolid
42.
43. Mucoadhesion Characterization Methods
Mucoadhesive polymers can be characterised by testing their
adhesion strength by –
A. in vitro/ ex vivo and
B. in vivo tests.
A. In Vitro Tests/ ex-vivo:
a. Tensile Strength Test:
It measures the force required
to break the adhesive bond
between a mucous
membrane and the
polymers.
The instruments usually
employed are modified
balances or tensile testers.
45. b. Shear Strength test:
• Shear stress measures the force that causes the bio- adhesive to slide
with respect to the mucus layer in a direction parallel to their plane
of contact. the weight required to detach the adhesive cup from the
mucosa was recorded using following formula
Force of adhesion 𝑁 =
𝑊𝑒𝑖𝑔ℎ𝑡 𝑔
1000
∗ 9.81
Bond strength(𝑁/𝑚2
)=
𝐹𝑜𝑟𝑐𝑒 𝑜𝑓𝑎𝑑ℎ𝑒𝑠𝑖𝑜𝑛 𝑁
𝑠𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎 𝑜𝑓 𝑐𝑢𝑝 (𝑚2)
c. Peel strength
• Peel strength is the amount of force or energy required for
tangential detachment of mucoadhesive formulation (cups) from
freshly excised bovine buccal mucosa.
• The test has shown limited use for mucoadhesive formulations.
However, for the patches it is of great value.
• The stress in this test is mainly focused at the edge of adhesive
system.
47. d. in vitro retention time : The time for complete erosion or detachment
of the formulation is recorded.
A mucoadhesive cup was pressed over the excised bovine buccal
mucosa for 30s > immersed in a beaker containing 500 ml of isotonic
phosphate buffer (pH 6.6) at 37 ± 0.2 °C. A stirrer was fitted at a
distance of 5 cm from the assembly and rotated at 25 rpm > time
recorded.
e. Ex vivo mucoadhesion time (for patches): The time required for
complete detachment of the patch from the mucosal surface was
recorded.
Phosphate buffer pH 6.6 (800 ml) was used as disintegration
medium maintained at 37 °C > Porcine check mucosa, 3 cm long,
was attached to the surface of a glass slab (vertically attached to the
apparatus)> patch was then hydrated from one surface with 15 μl
phosphate buffer and then it was brought into contact with the
mucosal membrane. The apparatus was allowed to move up and
down to immerse the patch completely in the buffer solution.
48. f. Rheological methods : An in vitro rheological method for polymeric solution
and gels was first proposed by Hassan and Gallo.
The viscosimetric changes of the system were monitored ensuing the
mucoadhesion force determination constituted by the polymer chosen and
mucin. This interaction force energy of the physical and chemical bonds of
the mucin–polymer then transformed into mechanical energy or work
which causes the change in viscosity.
It was exposed that the mixture of polymeric gel and mucin solution
showed more rheological response than the sum of the values of polymer
and mucin.
ηt = ηm + ηp + ηb
where ηt - coefficient of viscosity of the system, and
ηm and ηp are the coefficients of viscosity of mucin and bioadhesive
polymer, respectively.
The bioadhesion component, ηb, can be obtained as
ηb = ηt – ηm – ηp
The bioadhesion force, F, is given as
𝐹 = η 𝑏 𝜎 𝑤ℎ𝑒𝑟𝑒 𝜎= shear gradient
49. g. Other In Vitro Methods
i. Adhesion Weight Method
ii. Fluorescent Probe Method
iii. Flow Channel Method
iv. Mechanical Spectroscopic
Method
v. Falling Liquid Film Method
vi. Colloidal Gold Staining
Method
vii. Viscometric method
viii. Thumb Test
ix. Adhesion Number
x. Electrical Conductance
50. B. In vivo tests
The common in vivo tests to montior bioadhesion
include:
1. Use of radioisotopes
2. Use of gamma scintigraphy
3. Use of pharmacoscintigraphy
4. Use of electron paramagnetic resonance(EPR)
oximetry
5. X-ray studies
6. Isolated-loop technique
7. Bioavailability studies
51. Case study
Preparation and Evaluation of Buccal Bioadhesive Films
Containing Clotrimazole
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221005, India. Department of
Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Department of
Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Authors: 𝑺. 𝑺𝒊𝒏𝒈𝒉, 𝟏,𝟒
𝑺. 𝑱𝒂𝒊𝒏, 𝟏
𝑴. 𝑺. 𝑴𝒖𝒕𝒉𝒖, 𝟐
𝑺. 𝑻𝒊𝒘𝒂𝒓𝒊, 𝟏
𝐚𝐧𝐝, 𝑹. 𝑺. 𝑻𝒊𝒍𝒂𝒌 𝟑
Journal: AAPS PharmSciTech, Vol. 9, No. 2, June 2008
Abstract:
Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and
predetermined rate, provide distinct advantages over traditional dosage forms
The aim of present study was to prepare and evaluate buccal bioadhesive films
of clotrimazole for oral candidiasis.
The film was designed to release the drug at a concentration above the
minimum inhibitory concentration for a prolonged period of time so as to
reduce the frequency of administration of the available conventional dosage
forms.
Materials: Clotrimazole (CLZ), Sodium carboxy methyl cellulose (SCMC), carbopol
974 P (CP 974P), sabouraud dextrose agar (SDA) with chloramphenicol and
glycerol.
52. Preparation of the Buccal Bioadhesive Films (solvent casting
technique)
Weighed amount of CP
974P added to one-third
portion of DDW
CLZ dissolved in a minimum vol.
of ethanol > added to SCMC
contained in a dry beaker.
Add the other two-third
portion of DDW to the above
mixture with stirring to form
a homogeneous dispersion
add CP 974P solution &
glycerol to dispersion of
SCMC and stirred for 3
h
bubble-free gel poured
on a borosilicate glass
mould (10× 10×1.5 cm),
films were cut into smaller pieces
of 1×1 cm sizes, wrapped in
aluminum foil and stored in glass
containers
stirred for 1 h.
allowed to settle
>dried under hot air
at 40–45 °C for 16–20
h till a flexible film
formed
53.
54. Characterization:
• Weight Uniformity
• Thickness Testing
• Folding Endurance
• Drug Content Uniformity
• Microenvironment pH
• Swelling Studies of Buccal Bioadhesive CTZ Films
• Moisture Absorption
• Vapor Transmission
• Mechanical Characterization of the Films
• Bioadhesive Strength
• In vitro drug release
• Antifungal Efficacy of Buccal Bioadhesive Films
I. Preparation of the Agar Plates
II. Agar Diffusion Assay of CTZ Films
• Statistical Analysis(ANOVA; p<0.05)
59. • Discussion:
The microenvironment pH of different batches decreased with the
increasing concentration of CP 974P due to its acidic nature. The
decrease in pH may lead to mucosal irritation.
Folding endurance was found to more than 300 for each case,
indicative of reasonable flexibility of the films.
Adhesion occurs shortly after the beginning of swelling but the
bond formed between mucosal layer and polymer is not very strong.
The adhesion will increase with the degree of hydration until a
point where over hydration leads to an abrupt drop in adhesive
strength due to disentanglement at the polymer/tissue interface
.
60. Conclusion
• Present study showed the in-vitro efficacy of buccal bioadhesive films
of CTZ against C. albicans for prolonged period of time.
• Percent moisture absorbed decreased while vapor transmission rate
increased with increasing the concentration of CP 974P. Increase in CP
974P content reduced both the tensile strength and elongation break.
• The prepared buccal bioadhesive films provided a controlled and
prolonged in-vitro release of CTZ. Duration of growth inhibition
(antifungal activity) of buccal bioadhesive films of CTZ was
prolonged up to 6 h. This would be important for better patient
compliance because of the decrease in the frequency of
administration.
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no.5.1-5.30
• Mucoadhesion: A promising approach in drug delivery system;
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Reactive and Functional Polymers 100 (2016) 151–172.
• Controlled and Novel Drug Delivery by N.K.Jain. Pg no. 365-376.
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