International Journal of Contemporary Research and Review, Vol.

2 Issue 1[2011]21-30

Corresponding Author: Sheo Datta Maurya, Lecturer (Department of Pharmacy) IEC Group of
Institutions Greater Noida, INDIA
E-Mail- meetshiv23@gmail.com
Cell No-919999236301
Received: 16 Dec 2010; Accepted: 03 Jan 2011; Online: 13 Jan 2011

Research
Preparation and Evaluation of Floating Tablet of Famotidine Through Solid
Dispersion

Maurya SD1*,Tilak VK1, Dhakar RC1,Verma KK1,Soni U1, Gupta AK2,Sanwarmal3

1Department of Pharmacy, IEC Group of Institutions, Knowledge Park-I, Greater Noida, INDIA
2Amanath Pharmaceutical, Puducheri, Pandicheri, 605502, INDIA
3HIMT, College of Pharmacy, Knowledge Park-I, Greater Noida, INDIA- 201308

Abstract
The purpose of this investigation was to prepare a gastro retentive drug delivery system of fa-
motidine solid dispersion. Solid dispersion was prepared by melting method with PEG 4000 at
different concentration ratio, than it was dispend in floating tablet. Floating tablets of famotidine
were prepared employing two different grades of HPMC K4M and HPMC K15M; these grades of
HPMC were evaluated for their gel forming properties. The other polymer carbopol was added
for controlled release of drug from the formulation. Sodium bicarbonate was incorporated as a
gas-generating agent. The floating tablets were evaluated for uniformity of content, hardness, fria-
bility, in vitro buoyancy and dissolution studies. The prepared tablets exhibited satisfactory physi-
co-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet
swelled radially and axially during in vitro buoyancy studies.

Keywords: Famotidine, floating tablets, solid dispersion, in vitro buoyancy.

Introduction

Famotidine is a histamine H2-
receptor antagonist. It is widely
prescribed in gastric ulcers, duo-
denal ulcers, Zollinger-Ellison
syndrome and gastro esophageal
reflux disease. The low bioavaila-
bility (40-45%) and short biologi-
cal half life (2.5-4.0 hours) of fa-
motidine following oral admin-
istration favors development of
Due to low solubility of drug in water, it is need to make the solid dispersion of
drug with PEG 4000. The gastroretentive drug delivery systems can be retained
in the stomach and assist in improving the oral sustained delivery of drugs that
have an absorption window in a particular region of the gastrointestinal tract.2
These systems help in continuously releasing the drug before it reaches the ab-
sorption window, thus ensuring optimal bioavailability. It has been reported
that the oral treatment of gastric disorders with an H2 receptor antagonist like
famotidine or ranitidine used in combination with antacids promotes local de-
livery of these drugs to the receptor of parietal cell wall. Local delivery also in-
creases the stomach wall receptor site bioavailability and increases efficacy of
21

gastro retentative formulation.1 drugs to reduce acid which would efficiently reduced gastric acid secretion.3,4
Page
Over the years, a variety of solu-
bilization techniques have been
studied and widely used, by
many estimates up to 40 per cent
of new chemical entities discov-
ered by the pharmaceutical in-
dustry today are poorly soluble
or lipophilic compounds. The
solubility issues complicating the
delivery of these new drugs also
affect the delivery of many exist-
ing drugs.5 The various tech-
niques are available for en-
hancement of solubility. Solid
dispersion is one of the most
promising approaches for solubil-
ity enhancement. The term solid
dispersion refers to a group of
solid products consisting of at
least two different components,
generally a hydrophilic matrix
and a hydrophobic drug.6 The
matrix can be either crystalline or
amorphous. There are many
types of solid dispersions which
includes Simple eutectic mix-
tures, Solid solutions, Glass solu-
tions, amorphous precipitation in
a crystalline carrier.7
Different methods are also been
used for preparation of solid dis-
persions such as Melting method,
Solvent method, Melting solvent
method (melt evaporation), Melt
extrusion method, Lyophilisation
Technique, Melt Agglomeration
Process, The Use Of Surfactant,
Electrospinning and Super Criti-
cal Fluid (SCF) Technology.8
Materials and Methods5-18
Famotidine was received as a gift
sample from Ranbaxy Laborato-
ries Pvt Ltd, Gurgoan. Methocel
K4M and methocel K15M were
received as gift samples from
Colorcon Asia Pvt. Ltd., Goa, In-
dia, PEG 4000, Magnesium Stea-
rate, Hydrochloric Acid, Sodium
Bicarbonate, Lactose, and puri-
fied talc were provided by the
Department of pharmacy, IEC
Group of Institutions, Greater
Noida. All other ingredients were
of analytical grade.
Methods Preparation of solid
dispersion8
In melting or fusion method of preparation, polymer PEG 4000 at 58 0C in china-
dish was heated to a temperature, just above melting point 56OC and then drug
was added in 5 different weight ratio (1:1, 1:2, 1:3, 1:4, and 1:9) mixing the drug
with PEG 4000. The mixture was then cooled with constant stirring in ice bath, to
disperse the drug through out the matrix homogenously. The solidified mass of
drug-polyethylene glycol polymer system was often found to require storage of
one or more days in vacuum desiccators for hardening and case of powdering.
The final mass is then crushed, pulverized and passed through sieved no. 40.
Phase Solubility6
This study was carried out by the taking 10ml of distilled water in different vial.
To that excess amount of drug and PEG were added at different concentration.
Then vials kept on constant temperature water bath shaker for 24 hours. Then
the resulting solution was filtered, appropriate dilutions were made and ab-
sorbance was measured at 266nm by using UV spectrophotometer.
Dissolution Studies 11-12
The dissolution rate of plain drug and solid dispersion was determined using
tablet dissolution rate test USP Type-II apparatus (paddle type); 900 ml of 0.1N
HCl was used as dissolution medium maintained at temperature 37±0.50C and
100 rpm. Prepared solid dispersion equivalent to 10 mg of Famotidine was
weighed and filled in a capsule of suitable size. One capsule was placed in the
flask of the assembly and the paddle was immersed into the dissolution fluid to
the specified depth, the fluid was stirred by rotating the paddle at 100 rpm. 5ml
of samples were withdrawn and filtered through 0.45 μm filter at different time
intervals. The receptor phase was immediately replenished with equal volume of
o.1N HCL. Sink condition was maintained throughout the experiment. Absorb-
ance was recorded at 266 nm using UV spectrophotometer.
Fourier Transform Infrared Spectroscopy
The pallets of KBr and drug were prepared and examined under Perkin Elmer IR
spectrophotometer. The drug sample peaks are similar to reference standard.
About 1 mg of powdered drug mixed with approximately 100 mg of KBr (spec-
troscopic grade) in a glass mortar. The mixture was compressed into transparent
drotes with special designed moisture free atmosphere and IR spectra were ob-
tained on IR spectrophotometer. The scanning was done between 4000-400 cm-1.
The spectra so obtained were compared with reported in official compendia.
Characteristics peaks attributable to functional groups present in the molecule of
drug assigned to establish the identity.
Differential Scanning Calorimetry
Measurements were carried out using Mettler Toledo star system, Japan
equipped with liquid nitrogen sub ambient accessory. Calibration was carried
out using indium and Zinc as reference materials. Samples (5gm famotidine)
were sealed in aluminum pans and lids. DSC thermo grams were recorded at
heating rate of 100C/min. from 40-2000C temperature by using nitrogen gas as
effluent gas (80.0ml/min).
X-ray Analysis
X-ray Diffraction analyzed by using (x-ray generator and Goniometry Rigaku
Japan). X-ray diffract meter and cuk α radiation (α- 0.15418) parallel beam optics
was used with 1 mm entrance slit. The diffraction pattern was measured with
voltage 30 KV and current 100 mA in area of 10<20<90 in continuous scan mode
of 30/min (scan speed). λ= 1.54A0 was used and steps 0.02 were used for diffrac-
tion.
Preparation of Solid Dispersion Granule
Solid dispersion, Lactose and HPMC K4M or HPMC K15M were manually
blended homogenously with a mortar. The mixture was wetted using ethanol
(95%), passed through a 12-mesh screen and dried in a hot air oven at 400C over
night. The 12/16 fraction granules were collected and blended with carbopol
934P and magnesium stearate. Through the homogenously mixing of carbopol,
the granule was prepared.
22
Page
Flow Properties of Granules
The flow properties of granules
(before compression) were char-
acterized in terms of angle of re-
pose, Carr index. For determina-
tion of angle of repose, the gran-
ules were poured through the
walls of a funnel, which was fixed
at a position such that its lower
tip was at a height of exactly
2.0cm above hard surface. The granules were poured till the time when upper
tip of the pile surface touched the lower tip of the funnel. The tan-1 of the (height
of the pile / radius of its base) gave the angle of repose. Granules were poured
gently through a glass funnel into a graduated cylinder cut exactly to 10 ml
mark. Excess granules were removed using a spatula and the weight of the cyl-
inder with pellets required for filling the cylinder volume was calculated. The
cylinder was then tapped from a height of 2.0cm until the time when there was
no more decrease in the volume. Bulk density (db) and tapped density (dt) were
calculated. Carr index (IC) were calculated according to the equations given
IC = (dt– db)/dt

Preparation of Floating Tablets of Famotidine

The homogenous blend of granule was then compressed in to tablets on a single punch tablet press.
Table 1. Composition of (for 20 tablets) famotidine tablets.
S.No Ingredients (gm) FL-1 FL-2 FL-3 FL-4 FL-5 FL-6
1. Solid Dispersion 1.6 1.6 1.6 1.6 1.6 1.6
2. HPMC K4M 2.023 4.063 - 2.023 - 4.063
3. HPMC K15 M 2.023 - 4.063 2.023 4.063 -
4. Carbopol 934 0.938 0.938 0.938 1.25 1.25 1.25
5. Lactose 0.938 0.938 0.938 0.938 0.938 0.938
6. Sodium Bicar- 0.025 0.025 0.025 0.025 0.025 0.025
bonate

Uniformity of Content: Tablet Hardness:

This test was applicable to tablets
that contain less than 10 mg or
less than 10% w/w of active in-
gredient. Content of active ingre-
dient in tablets and capsules, tak-
en at random, was determined.
Crushed tablets and powder
equivalent to weight of tablet dis-
solved in 0.1 N HCl. Drug content
was calculated by measuring ab-
sorbance at wavelength 266 mm.
Friability:
Friability is the measure of tablet
strength. Roche friabilator was
used for testing the friability us-
ing the following procedure.
Twenty tablets were weighed
accurately and placed in the tum-
bling apparatus that revolves at
25 rpm dropping the tablets
through a distance of six inches
with each revolution. After 4 min,
the tablets were weighed and the
percentage loss in tablet weight
The hardness of tablet of each formulation was measured by Monsanto Hard-
ness Tester. The hardness was measured in items of kg/cm2
Floating Time:
Floating time was the time, the tablet floats in dissolution medium including
floating lag time. The time during which the dosage form remains buoyant were
measured.
Floating Lag Time:
This test was performed in beaker containing 100 ml 0.1 N HCl as a testing me-
dium maintained at 370C. The time required for the tablet to rise to the surface
and float was determined as floating lag time.
In vitro Dissolution Studies18
The release rate of Famotidine from floating tablets was determined using USP
Dissolution Testing Apparatus II (Paddle type). The dissolution test was per-
formed using 900 ml of 0.1 N HCl, at 37±0.50C and 100 rpm. A sample (10 ml) of
the solution was withdrawn from the dissolution apparatus hourly for 8 hrs, and
the samples were replaced with fresh dissolution medium. The samples were
filtered through Whatman filter paper no. 41. Absorbance of these solutions was
measured at 266 nm. Cumulative percentage drug release was calculated.
Short term stability studies
To assess the drug and formulation stability, stability studies were done accord-
ing to ICH guidelines. The promising formulation was tested for Short term test-
ing for a period of 1st month at 25°C ± 2°C/ 60% RH ± 5% and Accelerated test-
ing for a period of 2nd month at 40°C ± 2°C/ 75% RH ± 5%10, for their drug con-
23

was determined. tent and other parameters.

Page
Result and Discussion
Floating tablets of Famotidine
were developed to increase the
gastric residence time of the drug,
so that they can be retained in
stomach for longer time and help
in controlled release of drug. The
tablets were made using gel form-
ing polymers HPMC K4M,
HPMC K15M and CMC along
with effervescent agent Sodium
bicarbonate to optimize the drug content, in vitro buoyancy, swelling index, in
vitro drug dissolution studies. All the formulations were prepared by direct
compression method. Talc and Lactose was employed for their glidant and lu-
bricating properties. The prepared tablets of all the formulations were evaluated
for precompression parameters like angle of repose, bulk density, tapped density
and compressibility index and physical characters like tablet hardness, friability,
weight variation, buoyancy lag time, total floating time, in vitro drug release. The
main aim was to control the release of drug up to 8 hrs. The drug solubility ob-
tained at different concentration of PEG 4000. This show the relation that as the
concentration of PEG was increasing, solubility of drug was increased .Shows
that there was no any interaction between the drug and polymer in liquid phase.

Table 2. Dissolution rate of different formulations of solid dispersion

S.No. Time/min FS-1 FS-2 FS-3 FS-4 FS-5 FS-6

1. 0 0 0 0 0 0 0

2. 10 71.28 74.21 81.78 84.68 47.38 49.38

3. 20 84.08 86.8 89.46 91.68 62.42 66.42

4. 30 89.03 91.28 94.09 96.7 76.49 86.49

Preformulation Studies
The IR spectrum of the complete
formulation represents absorp-
tion peaks at 3411.84, 3500.78,
1658.7, 1637.0, 1110.92 cm-1. The
peaks that are shown above, all
indicate that the presence of a
particular group of characteristics
absorption peak in IR spectrum.
Which indicate the presence of
particular group in formulation?
So there was no any interaction between drug and polymer. Differential scan-
ning calorimetric (DSC) measurements were carried out using Metter Toledo
star system, the pure drug shows the peak at1680C, PEG shows at 620C, the solid
dispersion shows that there is no interaction between the drug and polymer in
solid state because both peaks are similar with references. The crystalinity of
drug (Famotidine), PEG 4000, and formulation was analyzed by using (X-ray
generator and Goniometry Rigaku) XRD technique was carried out using X-ray
diffractometer. The drug, different formulation of solid dispersion shows the
same peak of intensity in analysis of X-ray, at 2θ intensity was 11.86, 19.28,
23.10, 26.46 ,which shows that there is no change of crystalinity of the drug.

Figure .1: IR Spectra of plane drug

24
Page
Figure .2: IR Spectra of drug with polymer

Figure .3: X ray spectra of plane drug

Figur:4: X rays spectra of polymer

25
Page
 Figure .5: X rays spectra of solid dispersion
Precompression parameters of Angle of repose range from 32.45±.10 to 35.67±.20, Carr’s index range from 7.58
solid dispersion to 23.57 (Table no 3).
The formulations showed good
flow property and Carr’s index.

Table 3. Different evaluation parameter of solid dispersion granule.

S. No. Formulation Code Angle of re- Flow Rate Bulk Densi- Tapped Carr’s
pose ty Density Index
1. FS-1 33.69±.20 1.21±.01 0.68±.04 0.83±.06 21.86
2. FS-2 34.77±.30 1.17±.02 0.83±.03 0.93±.04 12.05

3. FS-3 35.67±.20 0.94±.02 0.76±.02 0.89±.06 16.70

4. FS-4 34.80±.30 0.97±.08 0.72±.01 0.91±.O5 24.72

5. FS-5 32.45±.10 1.17±.02 0.87±.02 0.93±.03 7.58

6. FS-6 35.10±.20 0.94±.02 0.68±.02 0.98±.O5 23.57

1.4

1.2

1
Solubility

0.8

0.6

0.4

0.2

0
0 2 4 6 8 10 12
% PEG concentration

Figure .6: Phase solubility study of drug

26
Page
 Figure. 7: % Drug release from different solid dispersions.
Post compression parameters of
solid dispersion tablets of Fa-
motidine
The shape of tablets of all formu-
lations remained off white,
smooth, flat faced circular with
no visible cracks. The thickness
and diameter of tablets was
measured by vernier calipers and
was ranged between 3.42 ± 0.043 mm to 3.72 ± 0.019 mm and 9.5 to 9.6 mm re-
spectively. The hardness of the tablets was measured by Monsanto tester (Ther-
mo Lab, Mumbai, India) and was in between 4.6 to 5.6 kg/cm2. The friability
was measured by friabilator (Roche friabilator) and was found to be 0.5 ± 0.03 to
0.08 ± 0.059%, which is an indication of satisfactory mechanical resistance of the
tablets. The drug content estimations showed values in the range of 97.27±.316 to
98.73±.255% which reflects good uniformity in drug content among different
formulations. All the tablets passed weight variation test as the % weight varia-
tion was within Pharmacopoeial limits. The results are shown in Table no 4.

Table 4. Different evaluation parameter of floating tablet.

S.No Formulation code Hardness Friability %Drug content

1. FL-1 4.6±0.74 0.04±.002 98.03±1.22

2. FL-2 5.5±0.82 0.03±.003 98.41±1.32

3. FL-3 5.6±0.46 0.05±.029 98.68±.962

4. FL-4 4.8±0.31 0.08±.059 98.69±1.68

5. FL-5 4.7±0.41 0.06±.052 98.73±.255

6. FL-6 4.6±0.28 0.03±.016 97.27±.316

In – Vitro release study
Comparative release study of dif-
ferent formulations shows that
FL-6 shows prolong release of
drug for a period more than the
other formulation FL-2, FL-3, FL-
4, FL-5, FL-6. After FL-6, FL-2
shows the better release then the other formulation. So the study indicates that
formulations containing HPMC K4M shows better release than the formulations
containing HPMC K15M. So the release of formulation are as follows FL-6 > FL-
2> FL-5> FL-4> FL-3 > FL-1. So the FL-6 was the best Formulation. When carbo-
pol was added in formulation it decrease the release of the drug from formula-
tion because as it increase the viscosity of the formulation.
27
Page
 Figure. 9: % Drug release of from different formulation of floating tablet

In vitro buoyancy studies
All the tablets were prepared by
direct compression. Sodium bi-
carbonate was added as gas gen-
erating agent. On contact with
dissolution medium (0.1N HCl),
carbon dioxide gas was generat-
ed. It was observed that the gas
generated is trapped and protect-
ed within gel, formed by hydra-
tion of polymer (HPMC), thus
decreasing the density of the tab-
let below 1 and tablet becomes
buoyant. All the batches of tablets
were found to exhibit short float-
ing lag time due to presence of sodium bicarbonate (Table 5). The tablets with
low viscosity grade HPMC K4M exhibited short floating lag time as compared
with formulations containing both HPM K4M and CMC. Reduction in HPMC
level in formulations prolonged the floating lag time. With reference to buoyan-
cy studies results it can be concluded that the batches containing HPMC K4M
polymers showed good floating lag time (FLT) and Total floating time (TFT).
Short term stability studies
The formulation (FL - 6) was selected for stability studies on the basis of in vitro
buoyancy and in vitro drug dissolution studies. The tablets were investigated at
25°C ± 2°C/ 60% RH ± 5% for 1st month and at 40°C ± 2°C/ 75% RH ± 5% for
2nd month. From the data, the formulation found to be stable under the condi-
tioned mentioned before since there was no significant change in the percentage
amount of drug content. Thus, it was found that the floating tablet of famotidine
remains stable under these storage conditions for at least 2 months.

Table 5. Floating lag time and total floating time of different formulations.
S.No Formulation code Floating lag time Total floating time

1. FL-1 0.04±.002 25.3±1.69

2. FL-2 0.03±.003 29.5±2.86
3. FL-3 0.05±.029 23.8±1.27
4. FL-4 0.08±.059 24.2±1.93
5. FL-5 0.06±.052 23.2±1.62
6. FL-6 0.03±.016 31.3±1.94
28
Page
 Figure.8: Floating behavior of tablet at different time

Table 6: Stability study of formulation FL-6.

Parameters 1st month 2nd month

25°C ± 2°C/ 60% RH ± 5% 40°C ± 2°C/ 75% RH ± 5%
Physical appearance Off white, flat faced Off white, flat faced
Weight variation (mg) 299.83±0.764 299.48± 299.48±0.921
Hardness (kg/cm2) 4.6±0.28 4.6±0.12
Friability 0.03±.016 0.029±.019
Drug content (%) 97.27±.316 96.97±.36
Total floating time (hrs) 31.3±1.94 30.45±5.84
In-vitro release (%) 90.20±0.468 89.85±0.321
Buoyancy on disturbing float float
29
Page
Acknowledgement
The author is highly obliged to
Ranbaxy Pvt. Ltd. For providing
gift sample of Famotidine, and
Department of Pharmacy, IEC
Group of Institutions, Greater
Noida for providing best lab facil-
ities necessary for completition of
research project.
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