FORMULATION AND EVALUATION OF BUCCAL DRUG DELIVERY SYSTEM

FORMULATION AND EVALUATION OF BUCCAL
DRUG DELIVERY SYSTEM
Submitted to:
Mrs. Suma R
Associate Professor
Department of Pharmaceutics
Al – Ameen College of Pharmacy
Presented by:
Adithya .B.S
M - Pharm 1st year
Department of Pharmaceutics
Al – Ameen College of Pharmacy

Contents:
 Introduction
 Types of dosage forms
 Formulation
 Evaluation
Department of Pharmaceutics Al-Ameen College of Pharmacy
2
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Introduction:
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 Administration of the desired drug through the buccal mucosal membrane lining of the
oral cavity.
 The product is placed between upper gingiva (gums) & cheek to treat local & systemic
conditions.

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Advantages Disadvantages:
3. Bitter in taste & irritant to
mucosa.
2. Eating and drinking difficulty.
1. Drugs are unstable at buccal
pH (6.5 to 7)
3. Avoids 1st pass metabolism &
acid/ enzyme metabolism.
2. Permeation is faster compared
with skin & TDDS.
1. Unconscious and coma patients.

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Buccal drug delivery system
1.
Buccal
tablets
2.
Buccal
patches
3.
Buccal
films
4.
Buccal
gels &
ointme
nts
5.
Buccal
sprays
6.
Fast
dissolvi
ng
buccal
tablets
7.
Buccal
wafers
8.
Buccal
micros
pheres
Types of dosage form used in buccal drug delivery system:

Formulation and evaluation for Buccal drug delivery
system:
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1) Muco-adhesive Buccal tablets:

Formulation of muco-adhesive buccal tablets:
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 Method use in the formulation of the muco-adhesive buccal tablets is Direct
compression.
All ingredients passed
through sieve no - 60
Required
quantity was
taken Blended powder
was compressed
2 batches
were prepared
Formulation continued………

Evaluation of muco-adhesive buccal tablets:
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a) Differential scanning
calorimetry:
1. Thermal properties of the excipients
with mefenamic acid were determined.
2. Samples weighing 2 mg were placed
in a sealed aluminum pan and were
heated constantly at the rate of
10°/minute from 25-450 ºC in air.
3. The nitrogen purge gas flow rate
was fixed to 25 mL/min.
1) Compatibility tests of mefanamic acid with excipients:
b) Fourier transform infrared
spectroscopy :
Infrared spectrum of mefenamic acid was
determined using KBr method. The base
line correction was done using dried KBr.
The spectrum of dried mixture of
mefenamic acid with KBr was run followed
by mefenamic acid with the various
excipients by using FTIR
spectrophotometer. The absorption
maximums in spectrum obtained with the
substance being studied must resemble in
position and relative intensity to the
reference standard spectrum

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Results: The compatibility studies were conducted for the pure drug(mefanamic acid) and the
excipients using both the FTIR and DSC.
a) DSC was conducted at 40°C for the period of one month and there was no significant drug
and excipient interaction was found and this confirms there is no thermal incompatibility
between the pure drug and the other ingredients.
b) FTIR – Physicochemical compatibility of the pure drug and the excipients were determined
using FTIR in which the results shows all the peaks of the active ingredients were seen when
the excipient was mixed with the active ingredient. This shows there is no incompatibility
between the pure drug and the excipients.

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Following are the results of both DSC and FTIR:
DSC of mefenamic acid:
DSC of sodium alginate

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DSC of hydropropylmethylcellllulose K4M
(HPMC K4M)
DSC of sodium carboxymethylcellulose (SCMC)

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DSC of magnesium stearate
DSC of excipients with mefanamic acid

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FTIR of mefenamic acid
FTIR of mefenamic acid with excipients initially and after one month at 40°C

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Result: All the tablets are within the acceptable range for tablet thickness with
values ranging from 3.71 mm to 3.80 mm. Tablet diameter of the tablets showed
values ranging from 12.01 mm to 12.08 mm, which fall within the acceptable range.
After 3 months of subjecting the tablets at 40 ºC/75% RH, the tablets are still within
the acceptable range for tablet thickness and diameter.
2) Tablet thickness and tablet diameter:
Test:
10 randomly
selected tablets
Tested
In vernier calipers
For
thickness &
diameter
It should be within
+ 5% variation of
standard value

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Result: The tablet hardness shows that all tablets are within the range. The results
show acceptable resistance of the tablet to shipping during storage and transport. All
the tablets fall within the in-house hardness range of 6.8 kg to 15 kg. Even after
stability testing, all tablets fall within the acceptable range.
3) Hardness test:
Test:
10 randomly
selected tablets
Measured
Using
Vanguard Pharmaceutical
Machinery, Inc.
The in-house
tablet hardness
ranges from 6.8
to 15 kg

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4) Friability:
The percent friability was calculated using the formula = % Friability = Wi x Wf x 100
Wi
Where Wi is the initial weight and Wf is the final weight of the tablet before and after the
friability test. The percent friability must not be more than 0.8% for new formulations
Result:The percent friability should not be more than 0.8% for new formulations. All tablets
are within range, therefore, the tablet is resistant to breaking due to storage and transportation.
Previously weighed
10 tablets
added
to
abrasion friabilator
Rotated @ 25 RPM
For 4 min about
100 revolution
After the
revolutions, the
tablets were placed
on a 10 sieve to
remove any loose
dust and were
weighed again
Test:

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5) Disintegration test:
Test:
Results: All the tablets disintegrated before 240 minutes. Even after 3 months of
stability test, all tablets still disintegrated within 240 minutes.
1) In 1000 mL beaker was filled with 900 mL of distilled
water and was maintained at a temperature of 37 + 0.5
ºC. Six tablets were placed in each of the cylindrical
tubes of the basket
2) The time taken to break the tablets into small particles
was recorded. The limit for buccal tablets is 4 hours .

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Test:
6) Content uniformity:
20 tablets were
triturated
powder
equivalent to 1
tablet was taken
dissolved in 100 mL
phosphate buffer (pH 6.8)
Heated at
37 ºC for
20 – 30 min
with stirring
The solution was filtered and
after suitable dilution was
subjected to UV
spectrophotometer at 279 nm
for measurement of
mefenamic acid content
Result: The tablet content should be within the range of 85% to 115% and no unit is outside the
range of 75% to 125% and the relative standard deviation should be less than or equal to 6%. All
fall within the range of 85% to 115% with a relative standard deviation of less than or equal to
6%. Even after 3 months of subjecting the tablets to 40 ºC/75% RH, all tablets fall within the
acceptable range

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Test: Twenty tablets were weighed together and separately using analytical balance. The
average weight and percent variation of the tablet were calculated. The weight uniformity was
determined according to USP specification .
Result: The specification of tablet weight with 500 mg is +5% difference. The tablet weights
should be 475 mg to 525 mg. All tablets fall within the specified limits and even after 3 months
of stability testing, all results fall within the range of 475 mg to 525 mg.
7) Weight variation test:

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Agar at 5% w/w
dissolved in hot water
and transferred it to
petri dish and allowed
it to solidify
6 tablets were pre
weighed and
placed in vacuum
overnight to
remove moisture
After drying it is
weighed and
placed over the
agar solidified
gel and incubated
at 37 ºC for 1 hrs
After that they
are removed
and the are
weighed for the
final weight
Percent moisture absorption was calculated using the formula:
% Moisture Absorption = Wi x Wf x 100
Wi
Where Wf is the final weight and Wi is the initial weight of the tablets
Test:
Result:Moisture absorption of the muco-adhesive buccal tablets is in the range of 14.07% to
16.65%. There was no significant change in the percent moisture absorption even after 3 months
of stability test, which shows that the tablets have suitable moisture absorption capacity
8) Moisture absorption study:

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Test:
 Salivary pH has range from 6.5 to 7.5.
 The tablets were allowed to swell for 2 hours in 1 mL of distilled water.
 The surface pH of the tablet was then measured using a digital pH meter.
 The pH electrode was placed near the surface of the tablet and was allowed to equilibrate for 1
minute before reading the measurement
9) Surface pH study:
Result: The salivary pH is 6.50 to 7.50. Since the surface pH of the buccal tablet is within the
limits of salivary pH, it shows that the tablet will not irritate the buccal mucosa.

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10) Swelling index study:
Petri dish with 1% agar gel
4 tablets weighed & placed
over it
Incubated it at 37 ºC+ 1 ºC.
After 0.5, 1, 1.5, 2, 2.5, 3 hours,
excess water on the surface was
carefully removed using the filter
paper without pressing. The
tablets were reweighed
Test:
swelling index was calculated using the formula:
Swelling Index = Wi x Wf x 100
Wi

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 The percent swelling of batch 1 and batch 2 baselines after 3 hours were 55.90% and
54.03%, respectively. After one to three months of subjecting the tablets to 40 ºC and
75% RH, the percent swelling of batch 1 was 58.86%, 53.83% and 54.89%, respectively,
while for batch 2, the percent swelling was 58.14%, 55.05% and 54.94%, respectively.
 Results of the analysis of variance for repeated measures showed that the interaction
effect of Time, Month, and Batch is not significant [F18,96=0.580, p=0.906] and even
after 3 months of stability test [F3,16=0.082, p=0.969], where the results show that there
was no significant difference from the results acquired after formulation at baseline.
Result:

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11) muco-adhesive/ bio-adhesive strength:
Buffer pH 6.8 & temp 37ºC
Test:

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Result: The mucoadhesive strength of batch 1 was 0.197, 0.196, 0.197, and 0.198,
respectively from 0 to 3 months of stability testing, while that of batch 2 was 0.200, 0.199,
0.198, and 0.198. There was no significant change in the mucoadhesive strength even after 3
months of stability test, which show that the buccal tablets have maintained their bioadhesive
strength. There was no significant difference in the mean mucoadhesive strength of the two
batches [F1, 64=0.993, p=0.323]. Likewise, the mean mucoadhesive strength at baseline and
after one, two and three months did not differ [F3, 64=0.102, p=0.958]. There was a sufficient
mucoadhesive strength of the tablets and it did not significantly change even after stability
studies for 3 months at 40 ºC and 75% RH

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• The residence time was tested using a modified USP dissolution apparatus. The
dissolution medium was 500 mL of phosphate buffer with pH of 6.8 maintained at
37 ºC.
• The porcine buccal mucosa was attached to a glass slide using an adhesive and was
tied to the paddle of the dissolution apparatus.
• The tablet was hydrated using 15 mcL of phosphate buffer and was placed in
intimate contact with the porcine buccal mucosa for 30 seconds.
• It was then immersed in the dissolution medium and was rotated at 25 rpm. The
time of displacement of the tablet from the mucosal surface was noted
Test:
12) Residence time:

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The average residence time of batch 1 and batch 2 were 14.03 minutes and 13.58 minutes,
respectively.
There was no significant difference in the residence time of the baseline and after 3 months
of stability studies
Result:

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13) Stability in human saliva:
Test:
Approximately 5 mL of human saliva were collected and placed in a petri dish. The buccal
tablet was placed in the petri dish and was put in an oven for 3 hours at 37 ºC + 0.2 ºC at
regular intervals with 0, 1, 2 and 3 hours. The buccal tablet was observed for changes in
appearance such as shape, color, collapse of the tablet, and change in pH
Result:
Changes in the buccal tablet would indicate that the drug is unstable in human saliva. The
results show that there were no changes in terms of color, shape, collapse of tablet and pH.
Same results were seen even at 1, 2, and 3 months of stability studies. Since there were no
changes, the buccal tablets have sufficient stability in human saliva

14) Drug release:
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• pH - 6.8
• Temp - 37 ºC + 0.5 ºC
• Rpm - 50rpm
• The sample at 5 mL was withdrawn at time
interval of 15, 30, 45, 60, 90, 120, 150, 180
minutes
• Determined in UV spectroscopy at 279nm
Test:

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Result:
The interaction effect of Time, Month, and Batch is significant [F8, 128=1.813, p<0.001]. The
mean percent release of the two batches [F1, 16=6.305, p=0.023] significantly differ,
indicating that batch 1 is significantly higher than batch 2. However, there is also no
significant difference in the mean percent release at baseline, after one, two and three months
[F3, 16 = 0.0829, p=0.497]. The main effect of Time [F8, 128=1434.733, p<0.001] was
significant, which shows that regardless of the batch and time, the mean percent release
continuously increases over time in minutes. Results show the potential of the formulation as
a mucoadhesive buccal tablet of mefenamic acid.

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15) Stability test:
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Test:
The tablets were stored for 3 months and the samples were tested after a period of 30, 60, and 90
days. The samples were analyzed using the quality control tests such as hardness, friability,
thickness, content uniformity, weight variation, and moisture absorption studies and in-vitro tests
such as swelling studies, mucoadhesive strength, stability in human saliva, and drug release
Result:
All tests conform within the specifications even after three months of subjecting the tablets to
40 ºC/75% RH

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Marketed products:

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2) Buccal films:

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Formulation of buccal films:

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25ml
Chitosan+PVP
Dispersed
21ml of aqueous solution
containing1.5% acetic acid
Stirred slowly
Magnetic stirrer
Until clear solution was obtained
1) Preparation of polymer solution:

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Tenoxicam dissolved in
10ml aq solution containing
1.5% acetic acid
+1.25ml PG
+5ml of absolute
ethanol
+4-5 drops of triethanolamine
were added to solubilize the
tenoxicam to form clear film
Drug
solution
Polymeric
solution
Mixed gently and
left over night
To remove
air bubbles
Casted on Teflon plates
diameter of 6.3cm
Dried in oven
at 40ºC
For 12h
Dried buccal film
2) Preparation of drug excipients solutions:
3) Preparation of Buccal films:

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1) Drug (TNX) content:
Test:
• dispersing a piece of 1cm2 in 100 mL methanol.
• The dispersion was sonicated for 15 min filtered
• absorbance was measured spectrophotometerically at ʎmax 368 nm.
Result:
The measured content of TNX in the prepared chitosan film was found to be between 1.87 and
2.10 mg (93.5–105% of the theoretical drug load) for all formulations
Evaluation of buccal films:

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2) Film thickness:
Test:
• Thickness of film strip in dimensions of 20 × 10 mm was measured using a hand-held
electronic digital caliper and an average value was reported.
• For each film, three patches (triplicate) were taken from different areas of the film, i.e., the
middle and two other positions
Result:
As observed these values range from 0.56 ± 0.04 mm to 1.02 ± 0.14 mm, which is in agreement
with the thickness suggested for ideal buccal films (50–1000 μm) to avoid any discomfort
upon application

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2) Swelling study:
• Patches were cut 1x1cm and weighed
• Then they are placed to swell on 1%w/v agar gel plate prepared in stimulated saliva
• Incubate at 37± 0.5 °C after 7h patch removed and excess water is removed and reweighed.
Swelling %: W2-W1 x 100
W1

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Instron universal testing machine
equipped with a 5 kg load cell at room
temperature
Thicknesses was
measured of
rectangular shaped
filmstrips (1 × 2 cm)
were
measured
Film held
b/w 2 grip
The upper grip was
withdrawn
speed of 20
mm/min
force and elongation
were
measured when the
films broke.
3) Mechanical properties:
Test:
Result:
Film F9 that contains the highest PVP concentration (5%) and the lowest concentration of
chitosan (0.5%), was the most flexible formula with high resistance as indicated by its
extension at break load value (4.13 ± 0.28 mm).

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4) In vitro bio adhesion:
Instron universal testing machine
equipped with a 5 kg load cell at room
temperature

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5) In vitro drug release:
Test:
1) The drug release from the films Buccal Film (1 × 1 cm), equivalent to 2 mg TNX/film, was
put in 250 ml conical flasks containing 100 ml simulated saliva as the dissolution medium
2) The dissolution medium was kept under sink condition. The flasks were shaken in a
thermostatic horizontal shaker at a speed of 50 rpm and adjusted at 37 ± 0.5 °C.
3) At predetermined time intervals of 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 7 h, samples of 2 ml were
withdrawn and replaced with fresh medium
4) The samples were filtered and analyzed by a UV–visible spectrophotometer at ʎmax 368 nm.
5) The in vitro release data were fitted into zero order-, first order-, Higuchi and Peppas-models
to assess the pattern of drug release from the different films

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Result:

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6) Thermal analysis:
Test:
• Differential scanning calorimetry (DSC) studies were carried out for optimized medicated
and non-medicated buccal films.
• compared to the individual film constituents (chitosan and PVP) to investigate the extent of
homogeneity and crystallinity of TNX using a calorimeter Samples weighing 3–5 mg were
sealed tightly in aluminum pans and heated at a rate of 10 °C/min, over a temperature range
of 25–250 °C.
• Nitrogen gas was used at a rate of 30 ml/min for purging. The data were logged using a TA
50I PC system equipped with Shimadzu software programs.

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(A), DSC scans of TNX (B), chitosan
(C), PVP (D), non-medicated buccal film
(E)optimized TNX loaded buccal film formula
Result:

50
7) X-ray powder diffraction:
• To evaluate the degree of drug crystallinity,
XRPD scans were acquired for medicated buccal
films compared to the film ingredients and non-
medicated films.
• using a RIGAKU diffractometer equipped with
curved graphite crystal monochromater, automatic
divergence slit and automatic controller PW/1710.
• The target used was Cu Kα radiation working at
40 KV and 40 mA (λkα = 1.5418 Å).
• The diffraction measures were accomplished
by means of continuous scan mode with
. 2θo range of 4° to 60°.
Test:

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Result:
(A)X-ray powder diffraction pattern of TNX, (B)chitosan, (C), PVP (D), nonmedicated
buccal film (E) optimized TNX loaded buccal film formula

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• The adhesion capacity of TNX mucoadhesive films was tested in six healthy female
volunteers aged between 18 and 40 years after informing them with the composition of the
formulation and signing a written informed consent.
• The volunteers were instructed to press the films against the buccal mucosa for 60 s [27].
• The volunteers were asked to record the residence time (time of complete erosion or
detachment of the film from the buccal mucus membrane) and to monitor for
fragmentation, irritation, bad taste, dry mouth or increase in salivary flow.
8) In vivo bioadhesion residence time:
Test:

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• human volunteers revealed that the film did not cause discomfort, but the taste was slightly
bitter; no severe salivation or mouth drying and no irritation were observed.
• The results showed that the optimized film in all six human volunteers had an in vivo
bioadhesion residence time of 1.25 ± 0.17 h and was subsequently detached from the buccal
mucosa and eroded.
• This decrease in the bioadhesion residence time could be attributed to the over hydration of
the polymer, which leads to the disentanglement at the polymer mucus interface and the
abrupt drop in the mucoadhesive strength.
• Additionally, it might be due to more severe conditions than those that usually influence in
vivo experiments, such as mouth movement when speaking and swallowing
Result:

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Marketed products:

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3) Buccal patches:

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Formulation of buccal patches:

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• Solvent casting method is used The mixture solutions of DG, HPMC K4 M, sodium
saccharin and atenolol were mixed well by means of a magnetic stirrer set at 400 rpm for 30
min and then homogenized using a homogenizer for 1 h at room temperature.
• Glycerine was added within the homogenized mixtures to act as a plasticizer. The mixtures
were sonicated again for 20 min to eliminate air bubbles.
• The sonicated mixtures were then transferred in the Petri dishes of 54 cm2 areas and also
were dried for 24 h at 45 ± 1 °C in an oven.
• The drug-free backing layer was prepared onto the atenolol-containing mucoadhesive
polymeric layers by using ethyl cellulose solution (1%) in ethyl alcohol by means of solvent-
casting method, and the prepared bilayered patches were dried at 45 ± 1 °C overnight.
• Then, the dried patches were collected from the Petri dishes,

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Evaluation of buccal patches:
1) Measurement of average weight and thickness:
Test:
• Buccal patches of 56 cm2 area size from all formulation batches were weighed separately by
using a digital electronic weighing balance to calculate the average weights of buccal patches
of each formulation batch.
• By using thickness gauze, the thickness of these prepared buccal patches was measured at
different points. Three buccal patches were picked randomly for every formulation batch, and
then measured
Result: The average weights of these newly prepared atenolol containing buccal patches (56 cm2
in size) were calculated within the range of 2.15 ± 0.07–2.22 ± 0.11 g.
Thethick nesses of these buccal patches were measured as 0.60 ± 0.07–0.65 ± 0.09mm.

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Test:
• Drug (here atenolol) contents within each prepared atenolol- containing buccal patch were
measured via dissolving 1 cm2 of buccal patches in the 100 ml of phosphate buffer (pH 6.8)
using a magnetic stirrer set at a speed of 600 rpm for 24 h at the room temperature.
• The solutions obtained after dissolving prepared atenolol-containing buccal patches were
filtered through the Whatman® filter paper (No. 42).
• Atenolol contents in the solutions were measured spectrophotometrically by UV–VIS
spectrophotometer at 275 nm wavelength (λmax) against the blank sample.
Result:
The drug contents in all these newly prepared atenolol-containing buccal patches were in-
between the range of 98.18 ± 2.63–99.12 ± 2.05%. This result designates that the drug (here
atenolol) was consistently dispersed throughout the drug containing a polymeric layer of the
buccal patches.
2) Determination of drug content:

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Test:
• The folding endurances of prepared atenolol-containing buccal patches were measured
manually by the procedure of repetitively folding at the same position until the breakages of
the tested patches.
• The number of folding times for tested buccal patches folded up the same position without
breakages of the patches was taken as the measure of folding endurance
3) Measurement of folding endurance:
Result:
• The highest folding endurance value was noticed for the buccal patch F 1 (28), whereas the
lowest endurance value was measured for the buccal patch F 4 (20).
• The results of the folding endurance study ensured the flexibility of these newly prepared
atenolol-containing buccal patches

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Test:
• Buccal patches containing atenolol were weighed correctly and then kept inside a desiccator
contained with calcium chloride (anhydrous).
• After completion of 3 days, buccal patches kept within the desiccator were removed and then
weighed using an electronic balance.
• The moisture content (%) of buccal patches was computed by the formula:
• Moisture content (%) = Initial weight − Final weight × 100
Initial weight.
Result:
• The moisture content (%) of all these newly prepared atenolol- containing buccal patches was
calculated, and this ranged in between 1.18 ± 0.07 and 1.73 ± 0.27.
• The lower moisture content within the buccal patches is well appreciable to avoid the chances
of microbial contaminations
4) Determination of moisture content:

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• The excised porcine buccal mucosal membrane was fixed and then tied to the open mouth of
a glass vial, which was filled up by the phosphate buffer (pH 6.8).
• Afterwards, the glass vial was compactly fixed at the center of a glass beaker filled up by the
phosphate buffer (pH 6.8) at the room temperature.
• The patches were glued to the lower part of the rubber stopper.
• A preload initial pressure by fingertip for 5 min was applied to set the tested buccal patch
and the excised porcine buccal mucosal membrane.
• The mass (in g) needed for detaching the tested patches from the buccal mucosal surface was
the value of the mucoadhesive strength (i.e. shear stress).
• From the results of the mucoadhesive strengths of various buccal patches tested, force
of adhesion and bonding strength of buccal patches was calculated
5) Ex vivo mucoadhesion study:
Test:

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Result:

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• The effectual diffusion area of the Franz diffusion cell used was determined as 1.67 cm2.
The receptor compartment (50 ml) of Franz diffusion cell filled up by phosphate buffer (pH
6.8) and 37 ± 0.5 °C of temperature was controlled throughout the experiment mag stirrer @
50rpm.
• A prepared atenolol-containing buccal patch was fixed under the occlusion on excised
porcine buccal mucosal membrane surface fitted between receptor and donor compartments
of the Franz diffusion cell used in the experiment.
• At regular intervals, 5 ml of samples from receptor compartment was withdrawn. After each
collection of samples from the Franz diffusion cell, 5 ml of fresh phosphate buffer (pH 6.8)
was replaced immediately.
6) Ex vivo drug permeation study: Test: Franz diffusion cell

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• Collected samples were filtered through the Whatman ® filter paper (No. 42), and atenolol
contents within the samples were measured spectrophotometrically using UV–VIS
spectrophotometer at 274 nm wavelength (λmax) against the blank sample.
Result:

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Test:
• The surface morphology of these atenolol-containing buccal patches was examined by SEM.
• The dried buccal patches were coated with the gold ion-sputter and then inspected under a
scanning electron microscope functioning at the working distance of 6 mm and the
accelerating voltage of 15 kV and × 5000 magnification.
Result: SEM of F4 because it gave best result
7) Scanning electron microscopy (SEM):

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Test:
• Drug–polymer compatibility of the prepared atenolol containing buccal patches was
examined by FTIR spectroscopy by potassium bromide pellet method.
• Pure atenolol and atenolol-containing buccal patches were scanned by a FTIR
spectrophotometer within the frequency range of 3600–600 cm−1 of the transmission mode
Result:
8) Fourier-transform infrared (FTIR) spectroscopy:

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Marketed products:

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3) Buccal gels:

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Formulation of buccal gels:

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Sodium
citrate
Added
To distilled water and stirred
till u get clear solution
+ Methyl
cellulose(P)
With
continues
stirring
Kept over night for hydration
+hydrocortisone
+triethanolamine
With
continues
stirring
Thus the
gels are
prepared

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Evaluation of buccal gels:
1)FT-IR studies:
Test:
• The potential for drug-polymers interactions was assessed using FTIR.
• KBr pellet method was used to spectroscopically analyze hydrocortisone, methyl cellulose and
formulation these pellets were scanned.
• from 4000 to 400 cm1 wavenumbers, and characteristic peaks were observed.
Result:
• Formulations displayed typical peaks of drugs and polymers while no new bands or point
changes existed suggesting no interaction between drug and polymers

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2)Appearance, clarity, and pH:
Test:
• Appearance and clarity were visually recorded in the light before and after gelling against the
white and black backgrounds.
• The pH is one of the most important parameters for in-situ gel formulation was directly
measured using a digital pH meter
Result:
• The pH of the formulations (F1–F4) was found to be pH 6.7, which concluded suitable for
aphthous ulcer.
• The typically formulated viscosity (F1–F4) was observed to be 290–440 cps.
• Higher viscosity is beneficial to quickly inject the in-situ gel into the oral cavity at a lower
temperature, whereas higher viscosity is beneficial for gels to stay in the oral mucosa for
longer periods

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3) Spreadability:
Test:
• Approximately 1 g of the gel was loaded in the middle of the glass plate (20 mm or 20
inches) to assess the spreadability of the gel.
• Each piece of glass was covered with another layer of the same thickness. First, the weight
of 1000 g on the upper side of the plate was gently applied, resulting in the gel spreading
out over the plates.
• The weight was removed after 1 min of application and the diameter of the spread area (cm)
was then determined

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Result:
• Evaluation of spreadability in terms of area covered by in situ gels per unit time and it was
related to in-situ gel viscosity.
• An increase in mucoadhesive polymer concentration restricted the distance traveled by in-
situ gel owing to the increased viscosity of the mucoadhesive polymer of in-situ gel.
• An optimal in-situ gel must have the correct gel strength so that it can be easily administered
and stored at the mucosa without leakage after administration

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4) Syringeability:
Test:
• All prepared formulations were transferred to the constant volume (2 ml) of a 5 ml syringe
placed with a 20-gauge needle.
• The solutions, which were quickly passed from the syringe, were called passing and difficult
to pass, as failed
Result:
• All formulations were found to be at preferable viscosity to be conveniently inserted into the
mouth cavity as the formulations were passed to the syringeability examination with a 20-
gauge needle.

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5) Gelling capacity:
Test:
• A visual approach was used to assess the gelling potential with which colored formulations
solution was stored.
• The gelling potential was estimated by inserting 2 ml of 6.8 pH phosphate buffer in a 10 ml
test tube and holding a temperature of 37 1 C.
• The phosphate buffer was supplemented with 1 ml of colored formulating solution.
• As the formulation comes into contact with the phosphate buffer, it was converted to a rigid
gel-like structure in a mimetic way
• The in vitro gelling ability was divided into three groups based on the freezing time and the
time required to dissolve the gel

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Result:
F3 and F4 shows higher gelling capacity

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6) Scanning electron microscopy:
Test:
• Scanning electron microscopy (SEM) was used to assess surface composition, structure, and
to investigate the broken and sectioned surface morphologies.
• SEM studies were conducted using dry formulation on an ion sputter-coated electron
microscope brush stub.
Result:
• SEM was used to analyze the composition and surface texture of the in-situ gel.
• Drug filled in-situ gel with both formulations (F1–F4) revealed common signs of
homogeneous mixing of polymers with drugs, where, no drug particles on the surface of
sample gels were observed

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Where A. SEM of formulation (F-1) B. SEM of formulation (F-2) C. SEM of
formulation (F-3) D. SEM of formulation (F-4).

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7) Differential scanning calorimetry:
Test:
• Differential scanning calorimeter (DSC) was used to assess stability tests of drug excipients
and also to detect further phase shifts, such as glass transformations, crystallization,
amorphous shapes of drugs and polymers.
• Samples of 10 mg were weighed and sealed in standard aluminum panels and then scanned at
a heating rate of 10 C/min over a temperature range from 50 C to 300 C.
Result:
• Compared to pure medication (hydrocortisone), in-situ gel formulation thermogram melting
point appeared to be reduced and the appearance of sharp and long endothermic peak
confirmed the amorphous nature of hydrocortisone

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8) Drug content analysis:
Test:
• The weighed amount of gel equivalent to 2 mg of drug was accurately taken and dissolved in
phosphate buffer (pH 6.8).
• The product content was measured against phosphate buffer at 242 nm (pH 6.8) using UV-
Visible Spectrophotometer-1800 and determined from the calibration curve.
Result:
• Product content indicates that the amount of product content was contained in the range of
76.4–94.7% for all product material formulations .

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9) Stability study:
Test:
• Stability analysis of optimal formulation was performed at 25 C/60% and 40 C/75% RH
according to the State Guidelines of the International Conference of Harmonization (ICH).
• Stable formulations were evaluated for pH, gelling ability, product quality and rheological
properties in vitro dissolution for three months.
Result:
• At 25 C/60% and 40 C/75% RH, the selected formulation F-4 was subjected to accelerated
stability studies for three months.
• Formulation (F-4) remained unchanged in appearance, pH, consistency, percentage drug
content, and viscosity

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Marketed products:

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1) Buccal Tablet :
Li KL, Castillo AL. Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic
acid. Brazilian Journal of Pharmaceutical Sciences. 2020;56.
2) Buccal Film :
Ashri LY, Abou El Ela AE, Ibrahim MA, Alshora DH, Naguib Mj. Optimization and evaluation
of chitosan buccal films containing tenoxicam for treating chronic periodontitis: In vitro and in
vivo studies. Journal of Drug Delivery Science and Technology. 2020;57:101720.
3) Buccal Patches:
Hasnain MS, Guru PR, Rishishwar P, Ali S, Ansari MT, Nayak AK. Atenolol-releasing buccal
patches made of Dillenia indica L. fruit gum: Preparation and ex vivo evaluations. SN Applied
Sciences. 2019;2(1).
Reference:

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4) Buccal gels:
A S, Ahmed MG, Gowda BH J. Preparation and evaluation of in-situ gels containing
hydrocortisone for the treatment of Aphthous ulcer. Journal of Oral Biology and Craniofacial
Research. 2021;11(2):269–76.

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