Indo American Journal of Pharmaceutical Research, 2014

ISSN NO: 2231-6876

FORMULATION AND COMPARATIVE EVALUATION OF MUCOADHESIVE BUCCAL

TABLET OF LOSARTAN POTASSIUM
Sayed Furquan Ahmed*, Dr.Imran Khan, Faizanurrab Saudagar
Department of Pharmaceutics, Ali Allana College of Pharmacy, Akkalkuwa, Nandurbar [MS].
ARTICLE INFO
Article history
Received 05/12/2014
Available online
29/12/2014

Keywords
Losartan Potassium,
HPMC K15M,
Nacmc,
Sodium Alginate,
Xanthan Gum,
Guar Gum,
Mucous Membrane.

ABSTRACT
The objective of this study was to develop mucoadhesive buccal tablets of Losartan
Potassium using both Synthetic and Natural mucoadhesive polymers and evaluate results of
both polymers. Losartan Potassium is Angiotensin receptor blocker having short biological
half-life (2hr), high first-pass metabolism and poor oral bioavailability (33%), hence an ideal
candidate for buccal delivery system. The buccal tablets of 150 mg were prepared by using
synthetic (Carbopol 934p as primary and HPMC K15M and SCMC as secondary polymer)
and natural polymers (Sodium Alginate as primary and Guar Gum and Xanthan Gum as
secondary polymers) separately in various concentrations by direct compression method,
twelve batches were formulated. Estimation ofLosartan potassium was carried out
spectrophotometrically at 250 nm. FTIR spectroscopy method revealed that there was no
interaction between Losartan potassium and polymers. The tablets were evaluated for
hardness, thickness, weight variation, drug content, and surface pH, swelling index, In-vitro
drug release, mucoadhesive strength and In-vitro residence time. Among synthetic polymers
FB3 and FB6 batches showed better results and from natural polymers batches FB9 and FB12
showed better results. The Ex-Vivo diffusion study of best release batches FB3, FB6, FB9 and
FB12 were performed by using Goat buccal membrane on Franz diffusion Cell Apparatus.
Data of In-vitro release from tablets were fed into kinetic models (Zero order, first order,
Higuchi and Korsmeyer-Peppas models) to explain release profiles. The best formulations
batch FB3 showed Korsmeryer-Peppas order release.

Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
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Please cite this article in press as Sayed Furquan Ahmed et al. Formulation and Comparative Evaluation of Mucoadhesive
Buccal Tablet of Losartan Potassium. Indo American Journal of Pharm Research.2014:4(12).

5850

Corresponding author
Sayed Furquan Ahmed
Department of Pharmaceutics,
Ali Allana College of Pharmacy,
Akkalkuwa, Nandurbar [MS]

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Sayed Furquan Ahmed et al.

ISSN NO: 2231-6876

INTRODUCTION
Mucoadhesive drug delivery systems offer benefits over conventional delivery methods in terms of extended residence time
of the drug at the site of application, a relatively large permeability of the mucus membranes that allow rapid uptake of a drug into the
systemic circulation, and enhanced bioavailability of therapeutic agents resulting from the avoidance of some of the bodys natural
defense mechanisms. Mucoadhesion, defined as the ability to adhere to the mucus gel layer, is a key element in the design of these
drug delivery systems. Buccal mucosa is an attractive route for systemic delivery of drugs since it is relatively permeable, with rich
blood supply. The problems such as high first-pass metabolism and drug degradation in the harsh gastrointestinal environment can be
circumvented by administering the drug via the buccal route and, buccal drug absorption can be promptly terminated in case of
toxicity by removing the dosage form from the buccal cavity. [1]
Losartan potassium is an angiotensin II receptor (type AT1) antagonist. The Losartan is an orally active agent that undergoes
substantial first-pass metabolism by cytochrome P450 enzymes. The Losartan is freely soluble in water and readily absorbed from the
gastrointestinal tract following oral administration. It undergoes first pass metabolism to form a carboxylic acid metabolite E-3174
(EXP-3174). The terminal elimination half-life of Losartan is about 2 hours. Hence, it is a suitable candidate for administration via the
buccal route. The bioavailability of Losartan is about 33%. [2, 3]
Drugs which are highly water soluble are considered difficult to deliver in the form of sustained or controlled release
formulation due to their susceptibility to dose dumping. Hence, an attempt is made to formulate a buccal tablet, to regulate the release
process of Losartan potassium using mocoadhesive polymers, with extended clinical effect, reduced dosing frequency and avoid dose
dumping.
MATERIALS AND METHOD
Materials
Losartan Potassium (Ipca Pharmaceuticals, Mumbai), Carbopol 934P, HPMC K15M, Sodium carboxy methyl cellulose, Sodium
Alginate, Xanthan Gum, Guar Gum S.D Fine Laboratory Mumbai.
METHODOLOGY
Matrix type buccal tablets of Losartan Potassium were formulated by direct compression method. The buccal tablets were
prepared by using both synthetic polymers and natural polymers separately in different proportion. The composition of different
formulations is shown in Table no 1 and Table no 2. The weighed drug, polymers and excipients were mixed homogeneously in a
glass mortar for 15 min. The mixture of 150 mg was then compressed using a 7 mm, flat punch in double-stroke using 9-station rotary
machine. (Karnavati Winepress II DL) [4-6]
Evaluation of mucoadhesive buccal tablets
Compatibility studies
The drug-excipient compatibility studies were carried out using Fourier Transform Infrared spectrophotometer (FTIR). IR
spectra of pure drug and mixture of drug excipients were recorded
Hardness[7]
The hardness of the tablets was determined using Monsanto Hardness tester. It is expressed in Kg/cm 2
Thickness[8]
The thickness of three randomly selected tablets from each formulation was determined in mm using a Vernier Caliper. The
mean and standard deviation values were calculated.
Weight Variation Test[9]
The weight variation test was performed as per procedure of IP. The weight (mg) of each of 10 individual tablets, selected
randomly from each formulation was determined by dusting each tablet off and placing it in an electronic balance. The individual
weight was compared with average weight for determination of percent deviation.

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Surface pH study[11]
An acidic or alkaline pH may cause irritation to the buccal mucosa. Three tablets from each batch were selected and allowed
to swell separately by keeping it in contact with distilled water (pH 6.5 0.05) for 2 hrs at room temperature. The pH was measured
by bringing the electrode in contact with the surface of the tablet and allowing it to equilibrate for 1 min.

5851

Content uniformity[10]
Ten tablets from each formulation were taken, crushed and mixed. From the mixture 20 mg of Losartan potassium equivalent
of mixture was extracted thoroughly with 100 mL of pH 6.8 phosphate buffer. The amount of drug present in each extract was
determined using UV spectrophotometer.

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Swelling Index[12]
Three buccal tablets were weighed individually (W1) and placed separately in 2% agar gel plates with the core facing the gel
surface and incubated at 37 1C. After every 2 h time interval until 8 h, the tablet was removed from the petri dish and excess
surface water was removed careful with blotting paper. The swollen tablet was then reweighed (W2) and the swelling index (SI) were
calculated using the formula given in equation.
Swelling Index = [(W2-W1) W1] 100
Where, W1 = initial weight of the tablet.
W2 = final weight of the tablet.
Mucoadhesion strength[13]
The apparatus used for testing bio adhesion was assembled in the laboratory Mucoadhesion strength of the tablet was
measured on a modified physical balance. A double beam physical balance was taken, the left pan was removed. To left arm of
balance a thick thread. To the bottom side of thread a glass stopper with uniform surface was tied. A clean 100 ml glass beaker was
placed below hanging in inverted position. Keep the surface of mucosa moist by phosphate buffer pH 6.8
In-Vitro Residence Time[14]
The ex vivo residence time was determined using a locally modified USP disintegration (Electrolab ED-2L) apparatus was
hydrated using phosphate buffer (pH 6.8) and the hydrated surface was brought in contact with the mucosal membrane. The glass slide
allowed moving up and down, so that the tablet was completely immersed in the buffer solution at the lowest point and was out at the
highest point. The time taken for complete displacement of the tablet from the mucosal surface was noted.
In vitro Dissolution Study [15]
The dissolution rates of the buccal tablets were studied using the USP type 2 apparatus at 370.5 C and 50 rpm. The buccal
tablet of Losartan Potassium was added to 900 ml of phosphate buffer (pH 6.8). The samples were withdrawn at the specific time
intervals and replaced with the fresh dissolution medium. The amount of Losartan Potassium released was determined
spectrophotometrically at 250 nm.
Ex-Vivo Diffusion Studies [16]
The in-vitro buccal drug permeation study of API through the gout buccal mucosa was performed using Franz diffusion cell
at 37 0.2 0C. Fresh buccal mucosa was mounted between the donor and receptor compartments. The buccal tablet was placed with
the core facing the mucosa and both compartments were clamped together. The donor compartment was filled with 1 ml of phosphate
buffer pH 6.8. The receptor compartment was filled with isotonic phosphate buffer pH 7.4 and the hydro dynamics in the receptor
compartment was maintained by stirring with a magnetic bead at 50 rpm. 1 ml samples were withdrawn at predetermined time
intervals and after appropriate dilution with isotonic phosphate buffer pH 7.4, analyzed at 250 nm using UV spectrophotometer.
Release kinetic studies[17]
To find out the mechanism of drug release from hydrophilic matrices, the in vitro release data was treated with different
kinetic models, namely zero order, first order, Higuchi and Korsemeyer-Peppas.

Losartan Potassium
Carbopol 934P
HPMC K15M
NaCMC
Chitosan
Mannitol
Lactose
Magnesium stearate
Talc
Total weight

Formulation Code
FB1 FB2 FB3
25
25
25
50
50
50
35
30
25
20
20
20
10
10
10
7
12
17
2
2
2
1
1
1
150 150 150

FB4
25
50
35
20
10
7
2
1
150

FB5
25
50
30
20
10
12
2
1
150

FB6
25
50
25
20
10
17
2
1
150

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Ingredients

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Table No. 1: Composition of mucoadhesive buccal tablet using synthetic polymers.

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Table No.2: Composition of mucoadhesive buccal tablet using synthetic polymers.

Ingredients
Losartan Potassium
Sodium Alginate
Guar gum
Xanthan gum
Chitosan
Mannitol
Lactose
Magnesium stearate
Talc
Total weight

Formulation Code
FB7 FB8 FB9
25
25
25
50
50
50
35
30
25
20
20
20
10
10
10
7
12
17
2
2
2
1
1
1
150 150 150

FB10
25
50
35
20
10
7
2
1
150

FB11
25
50
30
20
10
12
2
1
150

FB12
25
50
25
20
10
17
2
1
150

RESULT AND CONCLUSION

Compatibility studies
The incompatibility between the drug and excipients were studied by FTIR spectroscopy. The spectral data of pure drug and
various drug-excipient mixtures shows that there was no chemical incompatibility between drug and excipients used in the
formulation.
Table No.3: Physico-chemical evaluation of Losartan Potassium buccal tablets.
Batch Code

Hardness (kg/cm2)
5.10
4.63
4.03
4.93
4.43
3.90
4.07
3.80
3.57
3.93
3.67
3.37

Weight variation (%) Mean

SD
150.2 1.86
150.5 1.66
150.3 1.80
150.6 2.26
150.0 2.00
149.6 1.74
150.3 1.80
150.7 1.53
150.2 1.86
150.8 2.12
149.9 2.07
150.9 2.72

Drug Content (%)

92.31
90.67
97.47
91.49
94.07
96.18
95.12
94.77
96.30
93.25
94.42
95.24

Batch Code
FB1
FB2
FB3
FB4
FB5
FB6
FB7
FB8
FB9
FB10
FB11
FB12

Surface pH Mean SD
6.43 0.11
6.34 0.20
6.48 0.04
6.57 0.13
6.74 0.05
6.49 0.12
6.61 0.16
6.52 0.17
6.48 0.07
6.70 0.10
6.55 0.15
6.61 0.17

Swelling Index
(%)
103.12
98.67
96.67
101.33
98.67
94.67
102.00
98.00
95.33
98.67
96.00
93.33

Mucoadhesive
strength (gms)
18.34
17.09
16.87
16.45
16.36
15.76
15.12
15.03
14.76
13.47
13.19
12.89

Mucoadhesive
Time (Time)
6.15
5.41
5.15
6.09
5.34
5.09
5.56
5.36
5.18
6.03
5.32
5.02

5853

Table No.4: Physiochemical evaluation of Losartan Potassium buccal tablets.

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FB1
FB2
FB3
FB4
FB5
FB6
FB7
FB8
FB9
FB10
FB11
FB12

Thickness (mm) Mean

SD
3.33 0.02
3.30 0.01
3.31 0.03
3.32 0.03
3.34 0.02
3.33 0.04
2.47 0.01
2.45 0.03
2.46 0.04
2.45 0.02
2.43 0.03
2.42 0.05

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Table No.5: In-Vitro drug release profile.

Batch Code
FB1
FB2
FB3
FB4
FB5
FB6
FB7
FB8
FB9
FB10
FB11
FB12

Time In Hour
1
2
19.16 32.24
21.27 41.11
17.89 30.98
20.85 30.98
17.47 32.24
20.43 36.46
14.94 20.85
12.83 25.49
15.36 25.91
11.99 22.11
14.52 22.54
17.05 28.45

3
44.91
52.92
49.97
45.75
43.64
56.30
31.40
34.78
37.31
31.40
34.78
40.68

4
54.19
60.52
74.87
56.30
58.41
72.34
46.17
34.78
52.92
47.02
49.13
53.77

5
61.79
75.29
84.15
64.74
63.90
81.62
60.10
64.32
66.85
59.68
62.21
67.70

6
74.87
82.47
93.02
74.45
78.67
90.49
71.07
75.29
81.20
69.81
76.56
83.31

Table No. 6: Ex-Vivodiffusion study of FB3 FB6 FB9 FB12 Batches.

Batch Code
FB3
FB6
FB9
FB12

Time In Hour
1
2
13.40 25.40
13.70 24.23
11.99 22.54
12.83 24.63

3
35.51
34.36
30.56
29.72

4
48.71
44.91
38.58
43.22

5
58.79
56.73
49.95
51.24

6
64.63
62.64
58.84
60.08

Table No.7: In-vitro drug release data analysis.

First order
R
Slope

Matrix
R

Slope

0 .0937

0.1205

0.8510

1.6956

0.7688

-0.0078

Korsmayer-papas
R
Slope
0.9745 2.8765
n
k
0.1042 2.8765

Figure No 1 Drug release profile of synthetic polymers batches.

Hixson-crowell
R
Slope
0.1122

-0.0026

5854

FB3

Zero order
R
Slope

Page

Batch

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Sayed Furquan Ahmed et al.

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Figure No 2 Drug release profile of natural polymers batches.

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FigureNo3 Ex-vivo Diffusion Studies.

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Figure: 4 Kinetic Release Profile of Formulation Batch FB3

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CONCLUSION
The mucoadhesive buccal tablets of Losartan Potassium in effective treatment of hypertension were formulated using
synesthetic and natural polymers. The formulated buccal tablets were satisfactory in terms of physical parameters like hardness,
thickness, weight variation, drug content, swelling index, surface pH, etc.
From above study it has been concluded that mucoadhesive buccal tablet of Losartan Potassium were formulated using
synthetic polymers like HPMC K15M, NaCMC shows better in-vitro drug release as well as ex-vivo diffusion study as compare to
natural polymerslike Guar gum, xanthan gum.
The formulation batches containing HMPC K15M and NaCMC as secondary polymer with Carbopol 934P primary polymer
shows better mucoadhesive strength and ex-vivo residence time as compare to natural polymers using Guar gum and Xanthan gum
with primary polymer Sodium alginate at the same concentration.

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