Download formulation and evaluation of bilayer tablet of

Indo American Journal of Pharmaceutical Research, 2015
ISSN NO: 2231-6876
FORMULATION AND EVALUATION OF BILAYER TABLET OF FAMOTIDINE WITH
ANTACID LAYER
Kamal Kumar Bhatt*, shivani kala, Divya juyal
Himalayan Institute of Pharmacy & Research Rajawala, Dehradun (Uttarakhand).
ARTICLE INFO
Article history
Received 05/09/2015
Available online
30/09/2015
Keywords
Bilayer Tablet,
Famotidine,
Antacid,
HPMC K100M,
HPMC K4M.
ABSTRACT
In the present study bilayer tablet of famotidine with antacids (aluminium hydroxide and
magnesium hydroxide) layer are prepared. The inner sustained release layer of famotidine
consist controlee release polymer HPMC K4 M and HPMK100M at different concentration
.and the combination of citric acid ,tartaric acid and sodium bi carbonate used as a
effervescent for outer immediate release layer of antacid .The inner layer of famotidine shows
the sustained release effect up to 9 hrs. And the immediate release layer of antacids shows
rapid dispersion time between 8-12 seconds. The prepared tablets were evaluated for their
post compression parameters, physical characteristics and in-vitro release study. The drug
content of famotidine was found between the ranges of 98.25-99.30. The Cumulative percent
drug release of optimized formulation (FB5) after 10 hours were found to be 98.03 %. Fitting
the in-vitro drug release data in to krosmeyer-peppas model the n value found to be approx 1
that shows that all the six formulations followed the mechanism of diffusion. FB5
0
0
formulations were selected for stability studies stored at 30 C±2 C, 65 ± 5% RH and
subjected to stability studies up to 90 days. Drug content and cumulative percent drug release
after stored formulation for 45 days of optimized formulation FB5 were found to be 98.90.
The % similarity of cumulative percent drug release before and after was found to be 87%. It
showed that the formulations are physically and chemically stable.
Copy right © 2015 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Please cite this article in press as Kamal Kumar Bhatt et al. Formulation And Evaluation of Bilayer Tablet of Famotidine With
Antacid Layer. Indo American Journal of Pharmaceutical Research.2015:5(09).
2982
Corresponding author
Kamal Kumar Bhatt
Himalayan Institute of Pharmacy & Research Rajawala,
Dehradun (Uttarakhand).
kamal [email protected]
Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
INTRODUCTION
Famotidine is an oral drug that blocks the production of acid by acid producing cells present in the stomach. Famotidine
promote the healing of stomach and prevent ulcer when given at low dose for long period. For the quick relief to peptic ulcer pain and
to promoting the healing of peptic ulcer antacids are prescribed for the treatment of gastric ulcer. The oral treatment of gastric
disorders with an H2 receptor antagonist such as Famotidine with combination of antacids promotes local delivery of these drugs to
the receptor of parietal cell wall. Therefore, in this investigation attempt has been made to prepare S.R. tablet of Famotidine, so that
tablets are retained in the stomach for a longer period and local delivery of drug increases due to the contact of drug with its
absorption site at a constant rate for extend period of time and thus the bioavailability of the drug also increased . and also increases
the efficacy of drugs to reduce gastric acid secretion. Hence, this principle may improve systemic as well as local delivery of
Famotidine. H2 receptor antagonist used for the treatment of peptic ulcer or used in case of too much acid production in the stomach
by the approach of bi layer technique of Famotidine and antacid. the immediate layer of antacid neutralize the excessive acid present
in the stomach and then the sustained layer of Famotidine release and Famotidine bind with the H2 receptor located in the Basolateral
membrane of parietal cells and block the effect of histamine that control the excessive acid production in the stomach
BILAYER TECHNOLOGY
In last two decade the interest in layer technology of tablet increase because of the one or more active ingredient in a single
dose provides better treatment of disease and it provide control release of drug and improve the effect of therapy. Biayer tablet is the
new area for control release formulations. Bilayer tablet suitable for the sustained effect of tablet in which one layer is immediate
release and second is maintained dose. By the use of bilayer technology the drug re-administration or plasma fluctuation also be
minimized. Bilayer tablet is helpful design that reduce problem which are associated with the single layered tablet. Bilayer tablets
provide one of the important approaches where incompatible drugs, with different indication, and same drug with different release rate
can be added in a single unit. Bilayer tablet is suitable for sequential release of two drugs in combination, that individualized two
antipathetic substances or ingredient and also for sustained release tablet in which one layer is immediate release as starting dose and
next layer is maintenance dose. Many different types of compression are used to formulate bilayer tablets, like as simple single-sided
press to highly sophisticated equipment such as the courtoy-R292F [1]
Advantages of bilayer tablet
• Reduce cost of drug
• Minimizing dose dumping
• Suitable for large scale production
• Taste masking technique of bitter drugs or substance
• Separate physically or chemically incompatible ingredients [2,3]
Disadvantage of bilayer tablet
 Drug have bitter taste and objectionable odour or sensitive with oxygen require encapsulation or coating
 In case of children difficult to swallow and unconcision patient
 Drug have poor solubility, slow dissolution high absorption in GIT may be difficult to formulate.
 Insufficient hardness.
 The possibility of cross contamination between two layers [4,5]
MATERIAL & METHODS
MATERIAL USED:
Materials that are used in the formulation of bilayer tablet are purchased from various vendors or suppliers are listed below.
NAME
Famotidine
Aluminium hydroxide
Magnesium hydroxide
Citric acid
Magnesium stearate
Aerosil
Maize starch
Methocel k4m
Methocel k 100m
Calcium hydrogen phosphate
Mannitol
Microcrystalline cellulose ph101
Tartaric acid
Sodium bi carbonate
CATEGORY
Active
Antacid
Antacid
Effervescent
Lubricant
Glidant
Binder
Polymer
Polymer
Lubrication
Diluent
Filler
Effervescent
Effervescent
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VENDOR/SUPPLIER
Rakshit drug pvt.ltd.
Central drug house, Delhi
Central drug house, Delhi
Signet Chemical Corp. Pvt. Ltd
Nikita pharmaceutical
Evanik industries
Mulji motha & sons Pvt. Ltd.
Colorcon Pvt. Limited
Colorcon Pvt. Limited
Canton laboratories
M/S Roquette frères
DFE pharm India
Signet Chemical Corp. Pvt. Ltd
Central drug house, Delhi
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S.N.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
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Table 1 list of material used in formulation of double layer tablet.
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Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
PREPARATION OF BILAYER TABLET
Preparation of Granules of Immediate release Outer Layer (Antacid)
The ingredient listed in table.2 was weight accurately and passed through the sieve no 60. Aluminium hydroxide, magnesium
hydroxide, maize starch, citric acid and sodium bi carbonate were mixed homogeneously; aerosil and magnesium stearate was added
as a lubricant.
Preparation of Granules of Inner Layer
Wet granulation method: - Granules were prepared by using wet granulation technique. Microcrystalline cellulose, maize
starch, Hydroxypropyl methylcellulose and the active ingredients were mixed homogeneously. Water (quantity sufficient) was used as
a granulating agent. The granules were dried in fluid bed dryer. The dried granules were sieved through 40/60 meshes. Magnesium
stearate, colloidal anhydrous silica was added as a lubricant and the granules were compressed in to 65 station tablet punching
machine.
Compression of both layers to form bilayer tablet
The granules of inner layer were weight accurately and introduced in to the die size 12.8manually with the help of spatula.
The granules were allowed to punch and collected separately. Now the granules of outer layer were weight separately and allowed to
introduce in to die size 12.8, previously punched inner layer was also introduced in to the die cavity and allowed to punch
PREFORMULATION STUDIES:
Preformulation is the first step in the rational formulation of an active pharmaceutical ingredient (API). It is an investigation
of the physical-chemical properties of the drug substance, alone and in combination with excipients. Assessment of possible
incompatibilities between the drug and different excipients is an important part of preformulation.
Identification test:
The drug sample was authenticated using FT-IR and Melting Point test apparatus. Organoleptic characteristics of the drug
was observed and recorded by using descriptive terminology.
a. Physical Appearance:
b. Solubility
c. Melting Point test
d. FT- IR Characterization
e. Determination of analytical wavelength
f. Drug- excipient Compatibility study
Physical appearance
Physical appearance of drug was examined by organoleptic properties, colour, odour, taste, state. [6,7]
Solubility
Small amount of the drug was mixed with solvent in screw capped glass tube. The solution was examined physically for the absence
or presence of drug particles. [6]
Melting Point test
Melting point of Famotidine was determined by using digital auto melting point apparatus. A capillary fused at one end was
taken and a small quantity of famotidine was pushed in through the free end of capillary. The capillary was then placed in the well
provided space in digital melting point apparatus. The temperature at which the drug started to melt was noted. [6-8]
Determination of analytical wavelength:
Determination of λ max and Preparation of Standard Curve
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Standard solution:
The stock solution was diluted subsequently with 0.1N HCl to get a series of dilutions containing 2, 4, 6, 8 and 10 mg/ml.
One single dilution was selected and scanned in the wavelength range 200- 400 nm to get the UV spectrum and record the
characteristic peak, λmax. All other dilutions were then analyzed at that particular λmax to determine their absorbance for the
preparation of calibration curve of famotidine in 0.1 N HCl. Linearity, accuracy and precision were determined [9]
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Stock solution:
100 mg of famotidine was dissolved in sufficient amount of 0.1N HCl in a 100 ml volumetric flask and the solution was
made up to the mark with 0.1N HCl.
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FT- IR Characterization
The IR spectrum of drug was recorded using Fourier Transform Infra-Red Spectrophotometer (FT-IR) instrument. Nearly 1
mg of sample was thoroughly mixed with 100 mg of finely powdered KBr. The diffuse reflectance spectrum was recorded which is
similar to the transmittance spectra. [9,10].
Drug- excipient Compatibility study
The study of drug–excipients compatibility represents an important phase in the preformulation stage for the development of
all dosage forms. In fact, potential physical and chemical interactions between drugs and excipients can affect the chemical nature,
stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The ratio of drug to excipients used in
the study is often left to the discretion of the formulator, although some authors recommend the ratio encountered in the final
formulation. Often a 1:1 ratio is used to maximize the likelihood of interaction taking place and thus help in easier detection of
incompatibilities (El- Shattawy, 1984). Hence 1:1 ratio was selected in this study. The study was conducted in order to ensure that the
list of excipients used in the formulation does not cause any potential stability or compatibility problem. [10].
FORMULA FOR THE FORMULATION OF INNER LAYER TABLET
Table 2 List of ingredient required for formulation of famotidine S.R. tablet.
S.N.
1
2
3
4
5
6
7
8
INGRIDIENT
Famotidine
Microcrystalline cellulose
Starch
Methocel k4m
Methocel k 100m
Calcium hydrogen phosphate
Magnesium stearate
Aerosol
TOTAL
F1
40
120
20
10
5
3
2
200
FORMULATION
F2 F3 F4 F5
40
40
40
40
110 100 120 110
20
20
20
20
20
30
10
20
5
5
5
5
3
3
3
3
2
2
2
2
200 200 200 200
F6
40
100
20
30
5
3
2
200
FORMULA FOR THE FORMULATION OF OUTER LAYER TABLET
Table 3 List of ingredient required for formulation of antacid tablet.
S.N.
1
2
3
4
5
6
7
INGRIDIENT
Aluminium hydroxide
Magnesium hydroxide
Magnesium stearate
Tartaric acid
Citric acid
Maize starch
Aerosil
Sodium bi carbonate
TOTAL
QUANTITY (mg)
357
340
16.600
7.5
7.5
63.520
27.88
10
830
Angle of repose
The angle of repose of the powdered blend was determined by the funnel method. The accurately weight granules were taken
in a funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touched the apex of the heap of the
granules. The granules were allowed to flow through the funnel freely onto the surface. The diameter of the powder cone was
measured using the following equitation.
Ø = tan-1 (h/r)
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Flow Properties –
For the determination of frictional force, bulk density, tapped density, Measures of Powder Compressibility (cars index or
Hauser’s Ratio) or measurement of flow ability the Preformulation Parameters are needed before formulation.
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PRE-COMPRESSION PROPERTIESMost of the formulation include one or more combination of chemicals that are effect the preformulation parameters of main
active ingredient that are needed for compression. That’s why the precompression parameters evaluation is needed before final
compression according to the standard procedure.
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Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
Table 4 shown the value of Ø equal their flow property.
Angle of repose(Ѳ)
<25
25-30
30-40
>40
Where, h and r are the height and radius of the powder pile respectively.
Flow
Excellent
Good
Passable
Very poor
Bulk density
Both loose bulk density (LBD) and tapped density were determined, A quantity of the powder from each formula, previously
lightly shaken to break any agglomerates formed, was introduced into a 10 ml measuring cylinder, After the initial volume was
absorbed, the cylinder was allowed to fall under its one weight onto a hard surface. From the height of the 2.5 cm. LBD and TBD
were calculated using the following formulas.
LBD = weight of powder / volume of the packing.
TBD = weight of powder / tapped volume of the packing.
Compressibility index
The compressibility of the powdered blend was determined by Carr’s compressibility index.
Carr’s index (%) = (TBD - LBD) / TBD × 100
Table 5 Carr’s index Value (as per USP).
Carr’s index
5 – 15
12 – 16
18 – 21
2 – 35
33 – 38
>40
Properties
Excellent
Good
Fair to Passable
Poor
Very Poor
Very Very Poor
Hausner’s Ratio
The hausner’s ratio of the powder blend was determined by following formula.
HR = TBD / LBD
POST COMPRESSION PROPERTIESFor ensuring the tablet strength or uniformity in weight, uniformity in thickness of the tablet or various parameters such as
drug dissolution rate and amount of drug present in a single tablet (drug content) or dispersion time of tablet ,swelling property the
post compression parameters evaluation are require and their procedure and equipment used in evaluation are given below.
Hardness
2
The strength of tablet is expressed as tensile strength (Kg/cm ). The tablet crushing load, which is the force required to break
a tablet into pieces by compression. It was measured using a tablet hardness tester (Monsanto hardness tester).
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Where, w0 is the weight of the tablets before the test and w is the weight of the tablets after the test.
2986
Friability
The friability of the tablets was determined using Roche friabilater. This device subjects the tablets to the combined effect of
absorption and shocks in a plastic chamber revolving at a height at 6 inches in each revolution. Pre-weighted sample of taste was
placed in the friabilater and were subjected to 100 revolutions. Tablets were degusted using a soft muslin cloth and reweighted. The
friability (F) is gives by the formula.
F = (1-w0/w) × 100
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Kamal Kumar Bhatt et al.
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Weight Variation Test
Randomly selected 20 tablets were weighed individually and together in a single pan balance. The average weight was noted
and standard deviation was calculated. IP limit for weight variation in case of tablets weighting up to 120 mg is ± 10%, 120 mg to 300
mg is ± 7.5% and more than 300 mg is ± 5%.
PD= (W ) – (W
avg
) / (W
initial
avg
) x 100
Where PD= Percentage deviation,
W = Average weight of tablet,
avg
W
initial
= Individual weight of tablet.
Table 6 shown the average weight of tablet and acceptable range.
Average Weight Of A Tablet
80 mg or less
More than 80 mg and less than 250 mg
250 mg or more
Percentage Deviation
10
7.5
5
Swelling Index
The swelling of tablet involves the absorption of a liquid resulting in an increase in weight and volume. Liquid uptake by the
polymers results to saturation of capillary spaces within the polymer chain or hydration of macromolecule. To determine the extent of
matrix swelling, three tablets from each batch were weighed and placed in a Petri-dish containing 25 ml of 0.1N hydrochloric acid.
After each 2 hrs interval the tablets were removed from media, excess of media was wiped off by using filter paper and weighed again
up to 12 hrs. The swelling index was calculated using following formula. [11,12].
Swelling index= Final weight – initial weight/ Final weight x 100
Drug content
Ten randomly selected tablets were weight and average weight was calculated, then tablet were crushed then 10mg weight
and dissolve in 10ml of 0.1NHCL with the help of magnetic stirrer. This was the stock solution from which 1ml sample was
withdrawn and diluted to 10ml methanol. The content of each formulation was determined spectrophotometrically at 265 nm. [9]
In-vitro Dispersion Time
The USP device to test Dispersion uses 6 glass tubes that are 3 inches long open at top held against a 10 mesh screen at the
bottom end of the basket rack assembly. The tablets remain 2.5 cm below the surface of the liquid on their upward movement and
descend not closure than 2.5 cm from bottom of beaker. Tablet was placed in each of six tubes of the basket and apparatus was
operated at 28 to 32 cycles per minute. The temperature was maintained at 37 0 C ±20 C .The disintegration time was noted.
In- vitro Dissolution Study
The drug release studies were carried out using USP dissolution test apparatus at 100 rpm, 37 0 C ±0.50 C in 0.1 N HCL for 810 hrs. At different time interval 5 ml of sample were withdrawn and replaced with 5 ml of drug free dissolution medium. The sample
withdrawn were analyzed by UV spectrophotometer. Sample was analyses at 265 nm using UV-VIS spectrophotometry. [9]
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ZERO ORDER MODELS:
Drug dissolution from dosage form that do not disaggregate and release the drug slowly can be represented by the equation:
Q0 –Qt =K0t
Rearrangement of the equation yields:
Qt=Q0+K0t
Where
Qt is the amount of drug dissolved in time t
Q0 is the initial amount of drug in the solution
K0 is the zero order release constant expressed in units of concentration/time.
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KINETIC RELEASE (MATHEMATICAL MODELLING)
The data obtained from in-vitro release studies was treated by various conventional mathematical models (zero-order, firstorder, higuchi and korsmeyer-peppas) to determine the release mechanism from the designed double layer formulation. Selection of a
suitable release model was based on the values of R (correlation coefficient), k (release constant) and n (diffusion exponent) obtained
from the curve fitting of release data.
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Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
FIRST ORDER MODEL:
This model has been used to describe absorption and elimination of some drugs, although it is difficult to conceptualize this
mechanism on a theoretical basis. This release of the drug which followed first order kinetics can be expressed by the equation:
LogC=logC0-Kt/2.303
Where, C0 is the initial concentration of drug.
K is the first order rate constant, and t is the time.
The data obtained are plotted as log cumulative percentage of drug remaining vs. time which would be straight line with a slope of –
K/2.303.
KORSMEYER-PEPPAS MODEL
Korsmeyer derived a simple relationship which described drug release from a polymeric system equation to find out the
mechanism of drug release, first 60% drug release data were fitted in korsmeyer-peppas model.
Mt/M∞ =Ktn
Where, Mt/M ∞ is a fraction of drug released at time t,
K is the release rate constant and n is the release exponent.
Then n value is used to characterize the release mechanism of drug.
Table 7 Diffusion exponent and mechanism of diffusional Release from Swellable controlled-release System[13].
Slab
0.5
>0.5-<1.0
1.0
>1.0
>>1.0
Cylinder
0.45
>0.45-<0.89
0.89
>0.89
>1.0
Sphere
0.43
>0.43-<0.85
0.85
>0.85
>1.0
Drug release Mechanism
Fickian diffusion
Non Fickian
Zero-order release
Case II transport
Super Case II transport
STABILITY STUDIES
The stability studies were conducted for satisfactory formulation for 3 month. The satisfactory formulation sealed in
aluminium packaging and stored at 30±2°C with 65±5% RH for 3months.Samples were analyzed for physical parameters and drug
content.
RESULTS
RESULT OF PREFORMULATION STUDIES
Result of Physical appearance
Table 8 Physical appearance of famotidine.
Description
Colour
Odour
Taste
State
1
2
3
4
5
A white to pale yellowish white crystalline powder
White powder
Odourless
Bitter
Fine powder
RESULT OF SOLUBILITY STUDIES
SOLVENT
Distilled water
0.1N HCL
Methanol
Mineral acid
Glacial acetic acid &Diamethyl Formamide
Ethanol
OBSERVED SOLUBILITY
Very slightly soluble
Slightly soluble
Slightly soluble
Slightly soluble
Freely soluble
Insoluble
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S.N.
1
2
3
4
5
6
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Table 9 solubility study of Famotidine.
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Kamal Kumar Bhatt et al.
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RESULT OF MELTING POINT DETERMINATION
Table 10 Melting point determination of famotidine.
SAMPLE NO.
1
2
3
MELTING POINT (0C)
161-162
161-162
161-162
AVERAGE MELTING POINT(0C)
161.5
DETERMINATION OF ANALYTICAL WAVELENGTH
Determination of absorption maximum (λ ) in 0.1NHCL:
max
For determination of absorption, stock solution of 10ug/ml was prepared. The solution was scanned in the range of 200-400
nm in UV/visible spectroscopy. The λmax was found to be at 265nm.
Figure 1 Standard curve of famotidine.
RESULT OF IDENTIFICATION OF DRUG (FAMOTIDINE) THROUGH FTIR
Figure 2: FTIR scanning of famotidine.
1
2
3
4
WAVE
NUMBER(cm-1)
1800-1600
1600-1400
1200-1000
1000-800
PEAK
(REFERENCE)
1639
1601,1533
1146,1321
904
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PEAK
(SAMPLE)
1638.23
1601.59,1534.1
1146,1321
903.487
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S.NO
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Table 11 FTIR Spectra Range of Standard and Sample of Famotidine.
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Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
The drug sample as identified with FTIR spectroscopy and studies against standard famotidine. The peak of the sample was
identical as compare to standard and there was no major difference observed in absorbance peaks which shows the sample is pure and
free from impurities.
RESULT OF COMPATIBILITY STUDIES:
Figure 3 FT-IR spectrum of famotidine with polymers.
Table 12 FTIR spectrum of famotidine with polymer (HPMC K4M+HPMCK100M).
S.NO
1
2
3
4
WAVE NUMBER(cm-1)
1800-1600
1600-1400
1200-1000
1000-800
PEAK(REFERENCE)
1639
1601,1533
1146,1321
904
PEAK
(FAMOTIDINE+HPMCK4M+K100M)
1638.23
1601.59,1534.1
1146,1321
903.487
Figure 4 FT-IR spectrum of famotidine with mixture of excipient.
WAVE NUMBER (cm-1)
1
2
3
4
1800-1600
1600-1400
1200-1000
1000-800
PEAK
(REFERENCE)
1639
1601,1533
1146,1321
904
PEAK
(FAMOTIDINE+MIXTURE OF EXCIPIENTS)
1634
1601.59,1534.1
1146,1321
901.97
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S.N.
2990
Table 13 FTIR spectrum of famotidine with mixture of Excipients.
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RESULT OF EVALUATION OF PRECOMPRESSION STUDIES
FLOW PROPRTIES:
Table 14 flow properties of granules of inner layer.
S.N.
1
2
3
4
5
6
Formulation
Code
F1
F2
F3
F4
F5
F6
Bulk Density
Tapped Density
0.60
0.58
0.60
0.57
0.56
0.61
0.72
0.71
0.72
0.68
0.66
0.71
Carr’s
Index
16.66
18.42
16.66
16.17
15.15
14.08
Hausner’s
Ratio
1.20
1.22
1.20
1.19
1.17
1.16
Angle
Of Repose
23.60
22.90
23.58
24.20
22.50
24
Table 15 Flow properties of granules of outer layer.
S.N.
7
Formulation
Code
F7
Bulk Density
Tapped Density
0.75
0.82
Carr’s
Index
8.53
Hauser’s
Ratio
1.09
Angle
Of Repose
28.20
RESULT OF EVALUATION OF POST COMPRESSION PARAMETER
There are 6 formulation of double layer tablet which are prepared and they are evaluated for precompression and post
compression studies.
Table 16 Post compression parameters of inner core tablet.
S.N.
1
2
3
4
5
6
Formulation
Code
F1
F2
F3
F4
F5
F6
Uniformity of Weight (mg)
201
200
202
204
201
199
Thickness
(mm)
3.41
3.42
3.37
3.40
3.35
3.42
Hardness
(kg/cm2)
5.40
5.42
5.40
5.38
5.33
5.42
%Friability
0.59
0.50
0.56
0.54
0.49
0.62
Table 17 post compression parameter of bilayer (both inner or outer layer or complete) tablet.
S.N.
1
2
3
4
5
6
Formulation
Code
FB1
FB2
FB3
FB4
FB5
FB6
Uniformity of Weight (mg)
1031
1029
1031
1028
1031
1032
Hardness
(kg/cm2)
3.46
3.45
3.42
3.50
3.52
3.55
%Friability
0.61
0.62
0.63
0.60
0.59
0.61
Thickness
(mm)
12.6
12.6
12.6
12.6
12.5
12.5
SWELLING INDEX OF INNER LAYER
1
2
3
4
5
6
7
8
9
F1
10.6
17.2
26
34.8
40.2
48.5
56
61.2
-
F2
16.8
25.7
34.6
42.6
49.8
53.2
59.6
65.7
69.3
F3
19.3
32.7
41.7
42.8
53.9
62.8
70.8
77
83
Formulation code
F4
F5
F6
12.7 18.7 23.2
18.6 28
35.6
30.8 38.1 44.5
39.2 45.9 48.9
44
49.7 56.5
51.6 54.5 63.8
58
61
71
63.8 65
80.5
70.2 86.2
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Time in hrs
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Tablet 18 swelling index of inner core of tablet.
Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
Figure 5 swelling index of inner layer.
DISPERSION TIME
Table 19 dispersion time of outer layer.
S.N.
1
2
3
4
5
6
Formulation Code
FB1
FB2
FB3
FB4
FB5
FB6
Dispersion Time(Sec.)
Outer layer
10
9
11
10
8
12
Figure 6 dispersion time of inner layer.
RESULT OF DRUG CONTENT
Formulation code
FB1
FB2
FB3
FB4
FB5
FB6
Drug content Inner layer
98.65
98.55
99.30
98.76
99.25
98.99
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S.N.
1
2
3
4
5
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Table 20 drug content of inner layer.
Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
RESULT OF IN –VITRO DISSOLUTION STUDIES
Table 21 In –Vitro Dissolution Studies of Famotidine.
Time in
hours
1
2
3
4
5
6
7
8
9
10
F1
16.09
28.72
43.78
56.23
69.04
80.24
88.71
95.22
97.17
_
F2
11.88
25.50
41.96
53.55
64.10
75.03
82.33
90.27
95.97
97.30
% Release
F3
F4
10.15 15.30
23.21 26.09
36.62 38.71
48.99 54.20
61.49 68.00
73.21 79.59
79.98 90.79
89.36 94.17
94.57 96.26
96.91
_
F5
10.69
23.47
36.75
49.64
60.19
73.34
85.45
91.83
95.61
98.08
F6
9.75
22.95
36.88
47.04
62.53
69.83
83.89
88.71
92.61
96.52
Figure 7 Cumulative % drug release of inner layer (famotidine).
RESULTS OF STABILITY STUDIES
The optimized formulation (batch F5) stored at 40 ± 2°C/75 ± 5% was found stable. After storage at 40 ± 2°C/75 ± 5%,
cumulative percentage drug release, and % drug content were nearly similar to the initial results. So, it was clear that the drug and the
formulation were thermally stable as well as not affected by the high humidity at 40 ± 2°C/75 ± 5%. The similarity factor of the batch
after the stability study was found to be 87%when compared with the initial drug release profile. The comparative dissolution profile
of batch FB5 after stability study is shown table 1.17.
Table 22 stability studies of formulation FB5.
Duration of
period
Three month
Friability
Drug
content
98.90
0.60
Dispersion
time(sec.)
11
Thickness
12
Table 23 Dissolution profile of formulation FB5 after three months.
1
10.52
2
22.48
3
34.40
4
50
5
58.16
6
71.16
7
82.91
8
92.1
9
97.16
10
-
2993
Time in hours
FB5% Release
Page
Formulation
code
FB5
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Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
Figure 8 compression of cumulative % release profile of formulation FB5 after or before 3 month.
DISCUSSION
The Bilayer Tablet was formulated by using Famotidine as Inner Layer and Antacid combination (Aluminium Hydroxide &
Magnesium hydroxide) as outer layer. There are 6 formulation are formulated and evaluated.
Preformulation studies
 Solubility-famotidine was Slightly soluble in 0.1N HCL and Methanaol and freely soluble in glacial acetic acid and insoluble in
ethanol
 Melting point-the melting point range of famotidine between 161-162.
 Identification of drug through FTIR-The drug sample as identified with FTIR spectroscopy and studies against standard
famotidine. The peak of the sample was identical as compare to standard and there was no major difference observed in
absorbance peaks which shows the sample is pure and free from impurities.
 Compatability studies-The drug polymer compatibility studies are preformed with the help of FTIR spectrometry and there was
no major difference was show. Thus the polymers were compatible with drug.
Friability studiesThe % friability of bilayer tablet was found between 0.49-0.62.
Dispersion studiesThe dispersion time of outer layer of antacid was performed in 0.1N HCL.The time range between 8-12 sec. (0.8-0.12 min.)
that indicates the rapid dispersion time of outer layer.
Drug contentThe drug content of famotidine was found to be in range between 98.25 - 99.30 %.
In vitro drug release studiesIn the drug release studies of famotidine it was observed that increasing the amount of polymer decrease the drug release and
observed stability in drug release.
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Model Fitting of drug Release-the drug release profile of bilayer tablet of famotidine (inner layer) in 0.1 N HCL
 R2 value of zero order for inner layer found to be 0.974. to 0.999.
 R2 value of first order for inner layer found to be 0.951 to 0.979.
 R2 value of Higuchi release for inner layer found to be 0.901 to 0.933.
 n value of Korsmeyer Peppas for inner layer found to be 0.993 to 1.175.
 The n value of korsmeyer-peppas near about 1 and that’s indicates the drug release mechanism of the diffusion through swellable
matrix follows case II trsnsfer or super Case II transfer.
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Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
Stability studies –
The best formulation FB5 was taken for stability studies to see the effect of temperature and humidity in the formulation for 3
month. The stability result are satisfactory the % drug content were nearly similar to the initial results and The% similarity factor of
the batch FB5 after the stability study was found to be 87%when compared with the initial drug release profile. And there are no
difference is seen in drug physical appearance colour, size or shape.
So, it was clear that the drug and the formulation were thermally stable as well as not effected by the high humidity at 40 ±
2°C/75 ± 5%.
In the double layer tablet the outer layer is composed by antacid and inner layer contain famotidine the outer layer
formulation contain effervescent combination of sodium bi carbonate, citric acid and tartaric acid that release the outer layer as a faster
rate and inner layer contain sustained release polymer .so it was necessary that the dispersion time of outer layer are rapid and then the
inner layer show sustained release effect.
CONCLUSION
In the present study the bi layer tablet of Famotidine with antacid were designed, prepared and evaluated. The aim of the
study was to reduce and control of excessive acid production by the acid producing cells present in the stomach. Excessive acid in the
stomach cause various disease such as erosive esophagitis, gastric ulcer, zollinger-Ellison-syndrome, duodenal ulcer .Famotidine is a
H2 receptor antagonist used for the treatment of peptic ulcer or used in case of too much acid production in the stomach. By the
approach of bi layer tablet of Famotidine and antacid that control the excessive acid production in the stomach Famotidine bind with
the H2 receptor located in the basolateral membrane of parietal cells and block the effect of histamine .and the immediate layer of
antacid neutralize the excessive acid present in the stomach or give immediate relief from acidity.
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ACKNOWLEDGEMENT
Author is thankful to Sharon Bio Medicine Ltd. Dehradun for providing all the facilities related for this research Project.
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Vol 5, Issue 09, 2015.
Kamal Kumar Bhatt et al.
ISSN NO: 2231-6876
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