DESIGN AND CHARACTERIZATION OF ORAL MUCOADHESIVE BUCCAL FILMS OF FAMOTIDINE

Abstract

The goal in designing oral mucoadhesive buccal films of selective H2 receptor antagonist of famotidine is to increase the bioavailability, minimize the dose and reduce the side effects and to improve the patient compliance. Buccal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Buccal and sublingual sectors are the most commonly used routes for drug delivery and they may be used for the treatment of local or systemic diseases. The Aim of the study is related to the formulation and evaluation of oral mucoadhesive buccal films of famotidine by solvent casting technique. The Preparation contains 15 formulations by using different polymers like Hydroxy Propyl Methyl Cellulose-15 cps (HPMC), Carbopol (CP) and Poly vinyl pyrrolidone (PVP). The prepared batches of oral mucoadhesive buccal films of famotidine were evaluated for the physico chemical evaluations like surface pH, PMA, PML, swelling percentage, WVT, thickness, weight, folding endurance and drug content, the ex-vivo bucco adhesive strength, Ex-vivo permeation studies, in-vitro release studies and in-vivo release studies in rabbits were performed. The satisfactory results were obtained in all prepared formulations and based on the results F14 (150mg) +CP (20mg) +PVP (30mg) was the best one when compared to other.

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PHARMANEST
An International Journal of Advances in Pharmaceutical Sciences
Volume 6|Issue 4|July-August 2015|Pages xxxx-xxxx
Original Research Article
DESIGN AND CHARACTERIZATION OF ORAL MUCOADHESIVE BUCCAL FILMS OF FAMOTIDINE
S.RAMU*, SK.JAHIR ABBAS, D.SRINIVASA RAO, RAMAKRISHNA.G
Department of Pharmaceutics, K.C.Reddy Institute of Pharmaceutical Sciences, Jamgamaguntla Pallem, Medikondur, Guntur.
Author for Correspondence: samineni.ramu@gmail.com
ABSTRACT
The goal in designing oral mucoadhesive buccal films of selective H2 receptor antagonist of famotidine is to increase the bioavailability, minimize the dose and reduce the side effects and to
improve the patient compliance. Buccal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Buccal and
sublingual sectors are the most commonly used routes for drug delivery and they may be used for the treatment of local or systemic diseases. The Aim of the study is related to the
formulation and evaluation of oral mucoadhesive buccal films of famotidine by solvent casting technique. The Preparation contains 15 formulations by using different polymers like Hydroxy
Propyl Methyl Cellulose - 15 cps (HPMC), Carbopol (CP) and Poly vinyl pyrrolidone (PVP). The prepared batches of oral mucoadhesive buccal films of famotidine were evaluated for the
physico chemical evaluations like surface pH, PMA, PML, swelling percentage, WVT, thickness, weight, folding endurance and drug content, the ex-vivo bucco adhesive strength, Ex-vivo
permeation studies, in-vitro release studies and in-vivo release studies in rabbits were performed. The satisfactory results were obt ained in all prepared formulations and based on the
results F14 (150mg) +CP (20mg) +PVP (30mg) was the best one when compared to other.
Key Words: Hydroxy Propyl Methyl Cellulose (HPMC), Poly vinyl pyrrolidone (PVP) Percentage Moisture Absorption (PMA) Percentage Moisture Loss (PML) and Water Vapour
Transmission Rate (WVT).
INTRODUCTION
Buccal drug delivery is an alternative method of systemic
drug delivery that offers several advantages over both injectable
and enteral methods. The parenteral route may give excellent
bioavailability but suffers from poor patient compliance and various
risks such as anaphylaxis and extravasation infection. Peroral
administration of pharmaceutical compositions has some
drawbacks. For instance, it is difficult to keep the medicament at the
desired location so that it can be absorbed, distributed and
metabolized easily. These limitations have driven the development
of alternative routes of administration. Absorptive mucosa has been
attracting extensive research, as they offer many benefits, such as
noninvasive administration, rapid onset of action, good
bioavailability, avoiding of hepatic first pass metabolism and
reduced side effects1.
Buccal and sublingual sectors are the most commonly
used routes for drug delivery and they may be used for the
treatment of local or systemic diseases. The permeability of the oral
mucosa is probably related to the physical characteristics of the
tissues. The sublingual mucosa is more permeable and thinner than
the buccal mucosa and because of the considerable surface area
and high blood flow; it is a feasible site when a rapid onset is
desired. The sublingual route is generally used for drug delivery in
the treatment of acute disorders, but may not be always useful as
its surface is constantly washed by saliva and tongue activity which
makes it difficult to keep the dosage form in contact with the
mucosa.
Advantages
1. It is richly vascularized and more accessible for
administration and removal of dosage forms2.
2. High patient accessibility.
3. An expanse of smooth muscle and relatively immobile
mucosa, suitable for administration of retentive dosage
forms.
4. Direct access to systemic circulation through the internal
jugular vein bypasses drugs from hepatic first pass
metabolism, leading to high bioavailability.
5. Bypass exposure of the drugs to the gastrointestinal
fluids.
6. More rapid cellular recovery and achievement of a
localized site on smooth surface of buccal mucosa.
7. Low enzyme activity, suitability for drugs/ excipients that
mildly and reversibly damages or irritates the mucosa.
8. Non-invasive method of drug administration.
9. Facility to include permeation enhancer or enzyme
inhibitor or pH modifier in the formulation.
Disadvantages
1. Low permeability of buccal membrane2.
2. Small surface area (170 cm2).
3. Subsequent dilution of the drug due to continuous
secretion of saliva.
4. Inconvenience of patient when eating or drinking.
Limitations
1. Effect of salivary scavenging and accidental swallowing
of delivery system.
2. Barrier property of buccal mucosa.
3. Relatively small absorption area.
MATERIALS AND METHODS
Famotidine was obtained as a gift sample from Richer
pharmaceuticals, Hyderabad. Hydroxy Propyl methyl cellulose K4M
from Richer pharmaceuticals, Poly vinyl pyrrolidine, Carbopol were
obtained as a gift sample from Drugs India, Hyderabad.
Table 1 : The Composition of Buccal Films Prepared Using Famotidine
Formulation code
Polymers in mg
Solvents in ml
HPMC
CP
PVP
Ethanol (70 % v/v)
PG
F1
200
0
-
9.5
0.5
F2
190
10
-
9.5
0.5
F3
180
20
-
9.5
0.5
F4
170
30
-
9.5
0.5
F5
160
40
-
9.5
0.5
F6
150
50
-
9.5
0.5
F7
190
-
10
9.5
0.5
F8
180
-
20
9.5
0.5
F9
170
-
30
9.5
0.5
F10
160
-
40
9.5
0.5
F11
150
-
50
9.5
0.5
F12
150
40
10
9.5
0.5
F13
150
30
20
9.5
0.5
F14
150
20
30
9.5
0.5
F15
150
10
40
9.5
0.5
Famotidine: 20 mg
.

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FABRICATION OF DRUG FREE BUCCAL FILMS
The buccal mucoadhesive films were prepared by the
method of solvent casting technique3,4 employing ‘O’ shape ring
placed on a glass surface as substrate by using different polymers
like Hydroxy Propyl Methyl Cellulose - 15 cps (HPMC),
Carbopol(CP) and Poly vinyl pyrrolidone (PVP).
The calculated quantities of polymers were dispersed in
ethanol (70 %). The carbopol polymeric solution was neutralized
using triethanolamine. The polymeric solutions are levigation with
30 % w/w propylene glycol which served the purpose of plasticizer
as well as penetration enhancer. The solution was mixed
occasionally to get semisolid consistency. Then the solution was
subjected to sonication in a bath sonicator to remove the air
bubbles Then this were casted on a glass surface employing ‘O’
shape ring having 3.6 cm in diameter is covered with funnel to
controlling the evaporation of solvent and allowed to dry at room
temperature over night. The dried films were separated and the
backing membrane used was aluminium foil. Then the formulations
were stored in desiccators until further use5.
CONSTRUCTION OF CALIBRATION CURVE
An accurately weighed 100 mg of Famotidine was
dissolved in pH 7.4 phosphate buffer as per I.P and make up the
volume up to 100 ml in a volumetric flask, (Stock Solution: I, 1000
µg/ml) . From this 5 ml of solution were pipette out and make up the
volume up to 100 ml (Stock Solution: II, 50µg/ml). Then the aliquots
were prepared, whose concentration ranging from 0 to 30 µg/ml
and the absorbance were measured at 272 nm3 by using UV
Spectrophotometer Labomed, (Model No: 2602) against the reagent
blank.
PHYSICO - CHEMICAL EVALUATION
1. SURFACE pH
Buccal films were left to swell for 2 h on the surface of
an agar plate, prepared by dissolving 2 % (w/v) agar in warmed
isotonic phosphate buffer of pH 6.8 under stirring and then pouring
the solution into a petridish till gellig at room temperature. The
surface pH31 was measured by means of a pH paper placed on the
surface of the swollen patch. The mean of two reading was
recorded.
2. PERCENTAGE MOISTURE ABSORPTION (PMA)
The percent moisture absorption test6 was carried out to
check the physical stability of the buccal films at high humid
conditions. In the present study the moisture absorption capacity of
the films were determined as follows. Three 1cm diameter films
were cut out and weighed accurately then the films were placed in
desiccators containing saturated solution of aluminium chloride,
keeping the humidity inside the desiccators at 79.5 %. After 3 days
the films were removed, weighed and percentage moisture
absorption was calculated. Average percentage moisture
absorption of three films was found.
3. PERCENTAGE MOISTURE LOSS6 (PML)
This test was also carried to check the integrity of films
at dry condition. Three 1cm diameter films was cut out and
weighed accurately and kept in desiccators containing fused
anhydrous calcium chloride. After 72 hours the films were removed
and weighed. Average percentage moisture loss of three films was
found out.
4. SWELLING PERCENTAGE7 (%S)
A drug loaded films were placed in a thoroughly cleaned
petridish having 50 ml of pH 6.8 phosphate buffer. An increase in
the weight of the patch was noted in 15 min intervals for 60 min and
the weight was calculated. The swelling percentage was calculated
by using the following formula,
Where, % S - swelling percentage
Xt - the weight of swollen film after time t,
X0 -weight of film at zero time.
5. WATER VAPOUR TRANSMISSION RATE8 (WVT)
For this study vials of equal diameter were used as
transmission cells. These cells were washed thoroughly and dried
in an oven. About 1 g of calcium chloride was taken in the cell and
the polymeric films measuring 1 cm2 area were fixed over the brim
with the help of an adhesive. The cells were weighed accurately
and initial weight was recorded, and then kept in a closed
desiccators containing saturated solution of potassium chloride. The
humidity inside the desiccators was found in between 80 – 90 %
RH. The cells were taken out and weighed after 18, 36, 54 and 72
hrs. From increase in weights the amount of water vapour
transmitted and the rate at which water vapour transmitted were
calculated by using the following formula.
W V T = WL/S
Where, W is water vapour transmitted in mg, L is thickness of the
film in mm, S is exposed surface area in cm2.
6. THICKNESS6
The thickness of each film was measured by using a
digital vernier caliper at six different positions of the film and the
average thickness was calculated.
7. WEIGHT OF FILMS6
The weights of three films were taken and the weight
variation was calculated.
8. FOLDING ENDURANCE9
Folding endurance of the film was determined by
repeatedly folding one patch at the same place till it broke or folded
upto 300 times manually, which was considered satisfactory to
reveal good film properties. The number of times of film could be
folded at the same place without breaking gave the value of the
folding endurance. This test was done for three films.
9. DRUG CONTENT ESTIMATION6
A film was cut into three pieces of equal diameter were
taken in separate 100 ml of pH 6.8 phosphate buffer was added
and continuously stirred for 24 h. The solutions were filtered,
suitably diluted and analyzed at 272 nm in a UV Spectro
photometer. The average of drug content of three films was taken
as final reading.
MEASUREMENT OF BUCCOADHESIVE STRENGTH10
A modified balance method was used for determining
the ex-vivo buccoadhesive strength. Fresh sheep buccal mucosa
was obtained from a local slaughterhouse and used within 2 h of
slaughter. The mucosal membrane was separated by removing the
underlying fat and loose tissues. The membrane was washed with
distilled water and then with isotonic phosphate buffer (IPB) pH 6.8
as moistening fluid. Sheep Buccal mucosa was fixed on the plane
surface of glass slide attached (with adhesive tape) to bottom of
smaller beaker, kept inverted in 500 ml beaker attached to the
bigger beaker. Isotonic phosphate buffer pH 6.8 was added to the
beaker up to the upper surface inverted beaker with buccal mucosa.
The buccal film was stuck to the lower side of the upper clamp with
cyanoacrylate adhesive. The exposed patch surface was moistened
with IPB and left for 30 s for initial hydration and swelling. Then the
platform was slowly raised until the film surface came in contact
with mucosa. Two sides of the balance were made equal before
study by keeping a weight on the right hand pan. A weight of 5 g
was removed from the right hand pan, which lowered the pan along
with the patch over the mucosa. The balance was kept in this
position for 5 minutes contact time. Then weights were slowly
added to the right hand pan until the film detached from the
mucosal surface. This detachment force gave the buccoadhesive
strength of the buccal film in grams. The following parameters were
calculated from the bioadhesive strength.
Force of adhesion (N) = (Bioadhesive strength (g) ×9.8)/1000
Bond strength (N m–2) = Force of adhesion / surface area
EX-VIVO
PERMEATION STUDIES
An ex-vivo diffusion study of Famotidine was carried out
using a fresh sheep buccal mucosa11 using modified diffusion cell
at 37 ± 1°C. Fresh sheep buccal mucosa was mounted between
the donor and receptor compartments. Sheep Buccal mucosa was
tied to one end of an open-ended cylinder, which acts as
a donor compartment. The film should be placed in such
a way that it should be stuck on the mucous membrane.

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The receptor compartment was filled with isotonic phosphate
buffer pH 6.8. The assembly was maintained at 37 ºC and
stirred magnetically. Samples were withdrawn at predetermined
time intervals and analyzed using UV - Spectrophotometer at
272 nm.
IN-VIVO
DRUG RELEASE STUDY
Selection of Animals
Rabbits of 10 – 12 weeks old weighing 2.5 to 3 kg was
selected.
Method
A healthy rabbit12 weighing 2.5 to 3 kg was taken which
was already checked for absence of any diseases. The fore limbs
and hind limbs were tied into the iron rod of the mini operation
table; so that rabbit was in dorsal position (Fig.7.). The dose
of famotidine was adjusted based on the rabbit weight13 i.e the
optimized formulation F14 were cut to several pieces containing
about 1 mg of drug was placed in the buccal membrane with
the help of a clip. Dextrose solution was transfused
continuously throughout the period of study. Periodically 1
ml of blood sample was taken by syringe, which already
contained 1 ml of heparin solution to prevent blood
clotting. These blood samples were subjected for
centrifuging at 2,500 rpm for about 30 minutes. 1 ml of
supernatant was taken, and after suitable dilution, analyzed
at 272 nm using UV spectrophotometer.
RESULTS AND DISCUSSION
Table 2: Calibration Curve Data Of Famotidine
Concentration In
µg/Ml
Absorbance At 272 Nm
0
0
2
0.068
4
0.136
6
0.204
8
0.273
10
0.341
12
0.408
14
0.476
16
0.551
18
0.612
20
0.681
22
0.748
24
0.816
26
0.884
28
0.951
30
1.021
Figure 1: Calibration Curve Data of Famotidin
Table 3 : Physicochemical Evaluation of Buccal Films of Famotidine
Formulation Code
Surface pH  SD
PMA  SD
PML SD
Swelling Index  SD
F1
6.73±0.005
5.21±0.07
5.97±0.12
69.4±1.04
F2
6.79±0.005
7.32±0.04
5.14±0.72
99.67±0.69
F3
6.71±0.015
9.24±0.09
4.74±0.1
118.4±0.72
F4
6.64±0.050
10.32±0.11
4.14±0.2
124.15±0.99
F5
6.6±0.015
12.13±0.09
4.08±0.03
132.36±0.61
F6
6.52±0.03
14.21±0.06
3.88±0.02
138±0.85
F7
6.7±0.03
7.86±0.27
6.44±0.1
67.53±0.65
F8
6.8±0.015
6.18±0.13
7.13±0.08
69.7±0.72
F9
6.77±0.005
5.34±0.12
9.12±0.07
71.6±0.62
F10
6.8±0.001
4.12±0.13
10.06±0.06
78.6±1.07
F11
6.81±0.001
3.56±0.25
11.21±0.06
82.6±1.1
F12
6.71±0.001
13.02±0.23
4.84±0.08
86.9±0.9
F13
6.67±0.005
11.26±0.24
5.72±0.01
77.4±0.7
F14
6.63±0.005
9.89±0.22
6.13±0.02
72.53±0.6
F15
6.61±0.017
7.02±0.06
7.45±0.52
69.56±0.65

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Table 4: Physicochemical Evaluation of Buccal Films of Famotidine
Formulation Code
WTR  SD
Thickness
(mm)  SD
Weight of films in
mg  SD
Drug
Content
in mg
F1
10.58±0.35
0.24±0.01
180.93±1.55
19.7
F2
7.67±0.34
0.62±0.01
163.18±0.9
18.9
F3
7.17±0.34
0.47±0.01
171.53±0.81
18.1
F4
6.4±0.35
0.59±0.01
186.31±0.58
19.76
F5
5.98±0.08
0.85±0.02
191.37±0.85
18.76
F6
5.39±0.32
0.31±0.01
210.12±1.06
18.43
F7
10.87±0.35
0.22±0.02
181.17±1.79
19.7
F8
11.48±0.52
0.2±0.01
172.35±1.11
18.6
F9
11.58±0.43
0.23±0.01
172.31±1.11
19.1
F10
12.3±0.59
0.25±0.01
174.37±1.11
18.2
F11
12.44±0.48
0.31±0.01
174.94±1.66
19
F12
5.69±0.2
0.48±0.02
172.23±0.91
18.6
F13
5.91±0.38
0.43±0.01
170.37±0.65
18.9
F14
6.32±0.2
0.36±0.01
171.07±0.93
19.9
F15
6.94±0.31
0.32±0.01
182.43±0.5
19.3
Table 5: Measurement of Buccoadhesive Strength of Buccal Films of Famotidine
Formulation code
Buccoadhesive strength in gm
F1
15.4
F2
15.5
F3
16.6
F4
20.5
F5
27.8
F6
32.5
F7
15.3
F8
17.4
F9
19.8
F10
24.8
F11
26.7
F12
34.2
F13
34.8
F14
35.6
F15
33.4

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Table 6: In-Vitro Drug Release Data for Buccal Film F1-F15
TIME IN Hrs
F1
F2
F3
F4
F5
F6
F7
F8
0
0
0
0
0
0
0
0
0
1
18
24
19
14
9.8
7.2
16
14
2
28.2
30.1
29.6
22.4
20
17.2
24.6
22.1
3
35.2
37.6
36.1
33.9
29.4
25.6
33.2
32.6
4
47.2
49.6
48.6
44
41.6
39.2
44
43
5
55.4
57.1
55.6
52.4
50.1
48.6
50.4
49
6
67.2
70.1
68.1
64.2
62.4
59
58.2
57.4
7
74.6
77.9
75.4
71.6
69
67.2
70
68
8
83.2
85.6
84
79.2
76.4
73.1
75.2
74
9
88.6
90.2
89.6
84
81.2
79.6
82
81.2
10
95.2
96
95.6
92
89
87.2
90
88.9
11
-
-
-
98.1
96.2
94.4
96.6
95.2
TIME IN Hrs
F9
F10
F11
F12
F13
F14
F15
0
0
0
0
0
0
0
0
1
11
9
7.2
3.12
4.62
6.62
5.21
2
20
18.4
15.2
10.2
11.1
15.6
13.2
3
30
29.2
24.9
16
18.1
23.6
20.1
4
42.2
40.4
35.9
28.2
29.6
30.6
29.9
5
47.2
46
44.9
40.1
41.4
43.2
42.9
6
55.2
54.8
52
46.2
47.9
50.2
48.9
7
65
63
61
54
56.2
61.4
58.9
8
73.2
71
69
67
68
70.2
69.2
9
80
79
78
76.6
77.4
79.2
78.1
10
87.1
86.2
85
83.2
84
86.4
85
11
94
93.2
91
89.4
90.6
92.2
91
12
94.4
96.2
98.2
97
Graph 3: In-Vitro Drug Release Data For Buccal Film F1-F15
Table No: 7 Ex-Vivo Permeation Studies of Best Formulation (F 14)
Graph 4: Ex-Vivo Permeation Studies
Time (h)
Cumulative % Drug Release
0
0
1
5.16
2
11.12
3
21.02
4
27.41
5
40.23
6
47.42
7
58.31
8
64.4
9
73.2
10
79.4
11
87.6
12
94.23

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Table 8: In-Vivo Drug Release Data For Best Formulation F 14 [HPMC (150 Mg) + CP (20 Mg) + PVP (30 Mg)]
Graph 5:
In-Vivo
Drug Release Data For Best Formulation F 14
Table 9: In-Vitro In-Vivo Correlation Data
Time in hours
Cumulative % drug release
in-vivo
Cumulative % drug release
in-vitro
1
4.23
6.62
3
20.89
23.6
6
44.37
50.2
9
66.45
79.2
12
90.4
98.2
Graph 6: In-Vitro In-Vivo Correlation Data
DISCUSSION
The Famotidine buccal mucoadhesive films
were prepared by the method of solvent casting technique
employing ‘O’ shape ring placed on a glass surface as
substrate by using different polymers such as Hydroxy
Propyl Methyl Cellulose - 15 cps (HPMC), Carbopol-P
934 (CP) and Poly vinyl pyrrolidone (PVP). Ethanol (70
% v/v) is used as the solvents. Propylene glycol serves as
the plasticizer as well as penetration enhancer.
Triethanolamine was used to neutralize the carbopol
polymeric solution.
In-vitro drug release studies
Distinguishable difference was observed in
the release of Famotidine in all formulations. The results
and data of in vitro studies are shown in the Table and the
individual graphs were shown. Formulations F1, F2, F3
containing HPMC alone and Combination of carbopol and
HPMC gave a reasonable Famotidine release up to 10 h.
Formulations F4, F5 and F6 containing
Combination of carbopol and HPMC gave a reasonable
Famotidine release up to 11 h.
The formulations F1, F2, F3, F4, F5 and F6
has shown release 95.2%, 96%, 95.6 %, 98.1 %, 96.2 %
and 94.4 % respectively the drug release was Non fickian
release in case of formulations F1 and F2 and Super case
II transport type in of case of formulations F3, F4, F5 and
F6.
Formulations F7, F8, F9, F10 and F11
containing Combination of HPMC and PVP gave a
reasonable Famotidine release up to 11 h.
The formulations F7, F8, F9, F10, F11 and
F12 has shown release 96.6 % , 95.2 % ,94 %, 93.2 %,
and 91 % respectively The in-vitro drug release was Non
fickian release in case of formulations F7 and Super case
II transport type in of case of formulations F8, F9, F10
and F11.
Time in hours
Amount of drug release (mg)
Cumulative percentage drug release
1
0.84
4.23
3
4.178
20.89
6
8.956
44.37
9
13.29
66.45
12
18.08
90.4

P a g e | 59
PHARMANEST - An International Journal of Advances in Pharmaceutical Sciences
Volume 6|Issue 4| July - August 2015
Available online: http://www.pharmanest.net
Formulations F12, F13, F14 and F15
containing Combination of HPMC, CP and PVP gave a
reasonable Famotidine release up to 12 h.
Formulations F12, F13, F14 and F15 has
shown release 94.4% , 96.2% ,98.2% and 97%
respectively The in-vitro drug release was Non fickian
release in case of formulations F14 and Super case II
transport type in of case of formulations F12, F13 and
F15.
At pH 6.8, carbopol is present in ionized state
and as a result the polymeric network gets loosened
comparatively, attributing for the higher drug release. The
addition of PVP decreases the Famotidine release may
be due to enhancement in swelling of the polymer, which
in turn increases the barrier effect and decreases the drug
release, there by controlling the drug release
approximately 12 h.
The incorporation of carbopol and PVP into
HPMC films, the drug release was found to maximum at
the end of 12th h.
Ex-vivo permeation studies
The oral mucosa represents a barrier to drug
permeation and it is intermediate between skin epidermis
and the gut in its permeability characteristics. The
effectiveness of the buccal barrier and whether buccal
absorption could provide means for Famotidine
administration can be determined by Ex-vivo permeation
studies. Permeation studies were carried out on
formulation F 14. The cumulative amount of drug
permeated was 94.23 % maximum in 12 h.
In-vivo studies
In-vivo buccal diffusion studies were
conducted for the Famotidine buccal film F 14 in rabbits
showed zero order release pattern. The in-vivo studies of
buccal films of Famotidine in rabbits did not show any
inflammation or any other sensitization reactions at the
administration site.
SUMMARY AND CONCLUSION
The Famotidine buccal films were prepared by
solvent casting technique using ethanol (70%v/v) as a
solvent, employing o shape ring placed on a glass surface
as substrate and by using different polymers like Hydroxy
Propyl Methyl Cellulose-15cps (HPMC), Carbopol (CP)
and Poly Vinyl Pyrrolidine (PVP).The polymeric solutions
are levigated with 30%w/w propylene glycol which served
the purpose of plasticizer as well as penetration
enhancer. The prepared famotidine buccal films were
characterized based upon their physico-chemical
characteristics like surface PH, PMA, PML, swelling
percentage, WVT, thickness, weight, folding endurance
and drug content. the ex-vivo bucco adhesive strength,
Ex-vivo permeation studies, in-vitro release studies and
in-vivo release studies in rabbits were performed.
The satisfactory results were obtained in
all prepared formulations and based on the results F14
(150mg) +CP (20mg) +PVP (30mg) was the best one
when compared to other. Good correlation was observed
between in-vitro and in-vivo profile, revealed the ability of
the formulation to reproduce the in-vitro release pattern
through the biological membrane. Hence famotidine oral
mucoadhesive buccal films could be promising one as
they,increase bioavailability, minimize the dose,reduces
the side effects and improve patient compliance and also
famotidine might be a right and suitable candidate for oral
controlled drug delivery via mucoadhesive buccal films.
ACKNOWLEDGEMENT
The authors are thankful to Principle
Prof.D.Srinivasa rao, K.C.Reddy Institute of
Pharmaceutical Sciences, Jangamguntlapalem, for
providing the necessary facilities and help.
CONFLICT OF INTEREST
Authors declare no Conflict of Interest
REFERENCES
[1] Oliver A. Scholz, Andy Wolff, Axel Schumacher, Libero.
Giannola et al, Drug delivery from the oral cavity: focus on
a novel mechatronic delivery device. Drug Discovery
Today. March 2008; 13: 5/6.
[2] Yajaman Sudhakar, Ketousetuo Kuotsu,
A.K.Bandyopadhyay, Buccal bioadhesive drug delivery —
A promising option for orally less efficient drugs. Journal of
Controlled Release. 2006; 114: 15–40.
[3] Virag Szente, Karoly Suvegh , Tamas Marek , Prediction
of the stability of polymeric matrix tablets containing
Famotidine from the positron annihilation lifetime
distributions of their physical mixtures. Journal of
Pharmaceutical and Biomedical Analysis 2009; 49: 711–
714.
[4] Mona Semalty, A. Semalty and G. Kumar, Formulation
and characterization of mucoadhesive buccal films of
glipizide, Indian.J.Pharm.Sci 2008; 70(1):43-48.
[5] B.K. Satishbabu and B.P. Srinivasan, Preparation and
evaluation of buccoadhesive films of atenolol. Indian. J.
Pharm. Sci 2008; 70(2):175-179.
[6] M. Alagusundaram, B. Chengaiah, S. Ramkanth, S.
Angala Parameswari, C. Madhu Sudhana chetty and D.
Dhachinamoorthi, Formulation and evaluation of
mucoadhesive buccal films of Ranitidine. International
journal of pharmtech research. July-sept 2009; 1 (3):557-
563.
[7] Semalty, A, Bhojwani, M, Bhatt, G.K, Gupta, G.D,
Shrivastav, A.K, Design and evaluation of mucoadhesive
buccal films of Diltiazem hydrochloride. Indian.J. Pharm.
Sci. 2005, 67: 548- 52.
[8] T.E. Gopala Krishna Murthy and V. Sai Kishore, Effect of
casting solvent and polymer on permeability of Propranolol
hydrochloride through membrane controlled transdermal
drug delivery system. Int J Pharma Excip. 2006; July-
September, 68-71.
[9] Patel Hitesh R, Patel G N, Patel R B, Development of dual
layers drug delivery for motion sickness. International
journal of pharm tech research. 2009; 1 (2): 173-178.
[10] Sahini J, Raj S, Ahmad F, Khar R.K, Design and invitro
characterization of buccoadhesive drug delivery system of
insulin. Indian.J. Pharm. Sci. 2008; 70 (1): 61-65.
[11] Vishnu M. Patel, Bhupendra G. Prajapati, Madhabhai M.
Patel, Formulation, evaluation and comparison of
bilayered and multilayered mucoadhesive buccal devices
of Propranolol hydrochloride. AAPS PharmSciTech. 2007;
8(1):E1-E8.
[12] Subash Pillai, Saraswathi.R, Dilip.C, Design and
evaluation of buccal films of isoxsuprine hydrochloride.
Rjpbcs. 2010; 1(2)158-164.
[13] Ghosh MN. Some common evaluation techniques,
Fundamentals of Experimental Pharmacology, Third edn.,
Hilton and company, kotkotta:2005, p.177.
[14] Doijad R.C, Manvi F.V, Malleswara Rao V.S.N, Patel
V.S.N, Buccoadhesive drug delivery system of isosobide
dinitrate:formulation and evaluation. Indian.J. Pharm. Sci.
2006; 68(6):744-748.
HOW TO CITE THIS ARTICLE
S.Ramu*, Sk.Jahir Abbas, D.Srinivasa Rao, Ramakrishna.G. (2015 September 1).
Design and Characterization of Oral Mucoadhesive Buccal Films of
Famotidine.PHARMANEST,6(4) xxxx-xxxx. http://www.pharmanest.net