Original Article

Formulation and evaluation of sustained

release matrix tablet of rabeprazole using wet
granulation technique
Ruqaiyah Khan, Md Shamim Ashraf1, Muhammad Afzal, Imran Kazmi,
Mohammed Asadullah Jahangir2, Rajbala Singh, Ramesh Chandra3, Firoz Anwar

Department of
Pharmacology, Siddhartha
Institute of Pharmacy,
Dehradun, Uttarakhand,
1
Ibne Seena Pharmacy
College, Azmi Vidya
Nagri, Shahabad Dist.
Hardoi, UP, 2Department
of Pharmacology, Luqman
College of Pharmacy,
Gulbarga, Karnataka,
3
Department of
Pharmaceutics, Dehradun
Institute of Technology,
Dehradun, Uttarakhand,
India
Address for correspondence:
Dr.Muhammad Afzal,
Email:afzalgufran@gmail.
com
ABSTRACT
Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid
secretions. This drug claims to cause fastest acid separation(due to higher pKa), and more rapidly converts to
the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole
is dose dependent suppression of gastric acid secretion; without anticholinergic or H2blocking action. It
completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole
is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole
occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made
to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique
incorporating various polymers like HPMCE15, Carbopol934, and sodium carboxymethyl cellulose(CMC).
MaterialsandMethods:The Formulated tablets were evaluated for different physicochemical properties
like rheological properties, weight variation, thickness, hardness, % friability, invitro release studies and
drug content. Results: Studies revealed that all the physicochemical parameters comply with the official
standards. The invitro release studies exhibits the release up to 90%, over a prolonged period of time which
confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing
frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better
bioavailability, efficacy and potency, when compared with official standards.

Received : 231212
Review completed : 060513 KEY WORDS: Bioavailability, carcinogen, DENA, gatifloxacin, hepatocellular carcinoma, histology, HPMCE15,
Accepted : 230613 matrix, rabeprazole, sustained release

R etention of drug delivery systems in the stomach

prolongs overall gastrointestinal transit time improving
oral bioavailability of the drugs that are having site specific
absorption from the stomach or upper part of the small
intestine. Therefore different approaches have been proposed
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to retain the dosage form in the stomach including bioadhesive
systems, swelling, and expanding systems and delayed gastric
emptying devices to achieve gastric residence time for sustained
drug release.[1] The goal of any drug delivery system is to
provide a therapeutic amount of drug to the proper site in
the body to achieve promptly and then maintain the desired
drug concentration.[2] This deliberate control of drug release
is achieved in sustained release dosage form as it prolongs the
therapeutic effect by continuously releasing medication over an
extended time after administration of a single dose.[3]

DOI: The most employed method to modulate the sustained drug

10.4103/0975-7406.130961 release is to include it in a matrix system. Because of their
flexibility, hydrophilic polymer matrix systems are widely used

How to cite this article: Khan R, Ashraf M, Afzal M, Kazmi I, Jahangir MA, Singh R, Chandra R, Anwar F. Formulation and evaluation of sustained release
matrix tablet of rabeprazole using wet granulation technique. J Pharm Bioall Sci 2014;6:180-4.

180 Journal of Pharmacy and Bioallied Sciences July-September 2014 Vol 6 Issue 3

in oral controlled drug delivery to obtain a desirable drug release
profile, costeffectiveness, and broad regulatory acceptance.[4]
Matrix system are also favored because of their simplicity, patient
compliance than traditional drug delivery(TDS), which have
many drawbacks like repeated administration and fluctuation in
blood concentration level. In this type of drug delivery system,
the drug is homogeneously dispersed throughout the matrix
of crosslink of linear polymer chain.[5] It is assumed that from
this type of drug delivery system, drug molecule come out from
matrix by dissolution and then diffusion through the polymer
structure.[6] As the drug is released, the distance for diffusion
becomes greater and solid particles began to deplete. Most of
the highly watersoluble drugs, if not formulated properly, may
readily release the drug at a faster rate, and are likely to produce
toxic concentration.[6] Hydrophilic polymers have become
product of choice as an important ingredient for formulating
sustained release formulations of highly water soluble drugs.[7]
As the dissolution medium or biological fluid penetrates the
dosage form, the polymer swells and drug molecules begin to
move out of the system by diffusion at a rate determined by the
nature and composition of the polymer as well as formulation
technology.[8]
Sustained release matrix tablets prepared by wet granulation
technique using microcrystallineethyl cellulose polymer and
Bees wax showed good sustaining drug release concluding
that sustained release tablet could be successfully combined
with accurate control and prolongation of the drug release
patterns.[9,10]
Chemically Rabeprazole is designated as RS)-2([4(3methox
ypropoxy)3methylpyridin2yl] methylsulfinyl)1Hbenzo[d]
imidazole with molecular formula C18H21N3O3S. It is the
member of substituted benzimidazoles which inhibits the final
step in gastric secretion.
In vitro and animal studies have demonstrated that rabeprazole
is a more potent inhibitor of H+, K(+)ATPase and acid secretion
than omeprazole, and is a more rapid inhibitor of proton
pumps than omeprazole, lansoprazole, or pantoprazole. This
probably reflects rabeprazoles faster activation in the parietal
cell canaliculus.[11]
It inhibits the final transport of hydrogen ions(via exchange
with potassium ions) into the gastric lumen. Since the H+,
K+ATPase enzyme system is regarded as the acid(proton) pump
of the gastric mucosa, rabeprazole is known as a gastric acid
pump inhibitor. It does not have anticholinergic or histamine
H2receptor antagonist properties,[12] and is acidlabile. Once
Rabeprazole has left the stomach, absorption occurs within 1
hour of administration.[12] Elimination of rabeprazole occurs
very rapidly and almost entirely by metabolism to inactive or
less active metabolites. The differences in the metabolism
of these drugs may favorably or unfavorably affect their
pharmacodynamics(e.g.,acid suppression and plasma gastrin
profile), pharmacokinetics, and potential for drug interactions,
including those with the polymorphic cytochrome P450(CYP)
isoenzyme, CYP2C19.[13]
Journal of Pharmacy and Bioallied Sciences July-September 2014 Vol 6 Issue 3 181
Khan, etal.: Evaluation of sustained release rabeprazole tablet
It has short biological halflife(1-2h)that requires frequent
daily dosing and therapeutic use in acidrelated diseases that
necessitates its formulation into sustained release dosage
form.[14] This study is an attempt to formulate Rabeprazole as
sustained release matrix tablet for extending its release rate
for prolong period of time thus increasing the bioavailability.
Materials and Methods
Materials
Rabeprazole was received as a gift sample from Elder
Pharmaceuticals Pvt Ltd, Dehradun (India). The polymer
HPMC E15, Carbopol 934, Sodium CMC was procured
from Elder Pharmaceuticals Pvt Ltd, Dehradun(India). Talc,
Magnesium stearate was from S.D. Fine Chem. Ltd. Mumbai.
All the chemicals were of analytical grade.
Methods
Identification of pure drugs
Identification of Rabeprazole was examined by FTIR and
compared with the reference spectrum of drug.
Method used to estimate rabeprazole sodium
The drug Rabeprazole Sodium was dissolved in phosphate
buffer 7.2 to obtain 10 g/ml solutions. Further diluted with
the same buffer and scanned for maximum absorbance(max)
in a double beam UVVIS Spectrophotometer, between the UV
ranges from 200 to 400nm against phosphate buffer pH7.2
as blank; and max is found to be 287nm.
Prepration of calibration curve
Rabeprazole in water
Accurately 25mg of Rabeprazole was taken in a 100ml
volumetric flask. Sufficient amount of water was added to make
up the mark(stock solution). 10ml of the volume was made up
to the mark with water using the standard solution 1ml, 2ml,
4ml, 6ml, 8ml, 10ml that was withdrawn individually and
in each case the volume was made up to 10ml. The absorbance
of these solution were measured spectrophotometrically at



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Figure1: Standard curve of rabeprazole
 Khan, etal.: Evaluation of sustained release rabeprazole tablet

a suitable wavelength. The observed absorbance was plotted tablet are subjected to 100 freefalls of 6 inches in rotating drum
against concentration [Table1 and Figure1]. at 25rpm and then reweighed[Table3].

Fabrication of tablets F=100(1w0/w)

Wet granulations Determination of weight variation

All the polymers and active ingredients were passed through
sieve no.80 separately. Accurately weighed amount of polymers
and excipients were thoroughly mixed in glass mortar pestle. The
granules were prepared by wet granulation technique and passed
them to sieve no.20 and dried in hot air oven at 45C. The
granules were then mixed properly with magnesium stearate,
talc and punched with the help of automatic punching machine
to a desired hardness, shape, and size[Table2].
Determination of hardness of tablet
Randomly sampled 5 tablets in each batch of formulation
were used for the determination of hardness with the help of
Monsanto type hardness[Table3].[15]
Determination of friability
Roche friabilator is used in which approx. 6 gm of dedusted
Table1: Data for standard curve of rabeprazole in distilled
water
Conc. (Microgm/ml) Absorbance
1 0.091
2 0.15
4 0.289
6 0.417
8 0.535
10 0.674
20 tablets were selected at random and weighed accurately;
the average weight of the tablet was calculated. Then the
deviation of individual weight from the drug weight was
calculated[Table3].[15]
Determination of thickness of tablets
The individual crown to crown thickness of ten tablets was
determined using slide calipers for each batch[Table3].[16]
Measurement of the density of formulation
The approach densities of the tablet were calculated from
the volumes and masses in triplicate. The volumes(v) of the
cylindrical tablets were calculated from their heights(h) and
radius(r) are both determined with micrometer gauze using
the mathematical equation for a cylinder[Table3].[17]
V = r2h
Determination of drug content in tablets
3 tablets from each batch were selected randomly and transferred
to a 100ml volumetric flask were, filled up with 0.1N HCL.
Kept it for 48 hours then took 1ml from each of volumetric flask
was transferred to the test tubes samples were then filtered,
suitable diluted and analyzed spectrophotometrically at a
suitable wavelength[Table3].[9,12]

Angle of repose
Table2: Formulation chart
Ingredients Batch code(mg) It was determined by using funnel method. The accurately
(quantity/tab) F1 F2 F3 F4 F5 F6
weighed spheres were taken in funnel, and were adjusted in such
a way that the tip of funnel just touches the apex of the heap
Rabeprazole 50 50 50 50 50 50
HPMC E15 50 100 50
of blends. The blends were allowed to flow through the funnel,
Carbopol 934 50 100 50 freely on the surface. The diameter of the powder concentration
Sodium CMC 50 50 was measured; angle of repose was calculated by using following
Lactose 150 100 100 100 equation [Table3].[15,16]
Talc 3 3 3 3 3 3
Mag. state 2 2 2 2 2 2
Tan = h/r

Table3: Evaluation of different parameters

Batch code Evaluating parameters
Hardness Thickness Weight variation(%) Angle of repose Bulk density Tapped density Carrs Drug content
kg/cm2 (cm) () gm/cm3 gm/cm3 index % %
F1 3 0.3 2.4 14.93 0.45 0.55 18.18 95.3
F2 3.5 0.35 3.1 22.26 0.63 0.79 20.25 98.9
F3 4 0.4 2.8 30.43 0.57 0.62 8.06 90.2
F4 3 0.3 2.7 28.21 0.48 0.57 15.78 91.2
F5 3 0.4 1.3 26.43 0.59 0.68 13.23 94.6
F6 4.0 0.35 2.6 25.21 0.49 0.53 7.54 97.2

182 Journal of Pharmacy and Bioallied Sciences July-September 2014 Vol 6 Issue 3
 Khan, etal.: Evaluation of sustained release rabeprazole tablet

Where in the weight of individual tablet from average value and the
h = height of pile variation was found within the limit [Table3].
= angle of repose
R = radius of base pile The thickness of the formulated tablets was within the range
25 = excellent flow of 0.3 to 0.4cm[Table3].
25-35 = good flow
30-40 = passable The drug content study was performed on 3 randomly selected
>40 = very poor flow samples from each batch. The result indicates that the content
of Rabeprazole of all batches was found within the range of
Bulk density 90% to 97%.

Apparent bulk density was measured by pouring the preweighed The formulated granules of different formulations were
blend into a graduated cylinder. The bulk volume of the blend evaluated for their rheological properties like angle of repose,
was determined, and then the bulk density was calculated by bulk density, tapped density, and Carrs index [Table3]. The
using the formula[Table3].[18] result of angle of repose indicates the good flow properties of all
the formulated granules. The bulk density, tapped density, and
Pb=M/VT Carrs index values also suggested that the prepared granules
have good property regarding flow ability.
Tapped density
In vitro releases of rabeprazole from different batches were
The measuring cylinder containing a known mass of blend was studied using USPII paddle type dissolution apparatus in acidic
tapped for a fixed time and the min. Volume(Wt) occupied pH for 2 hrs and in phosphate buffer for 10 hrs.
in the cylinder was measured; the tapped density(pt) was
calculated by using the following formula[Table3].[18] The different concentrations of different polymers showed
different release patterns. From the release data of different
Pt=M/vt formulations [Tables4 and 5, it was observed that the release
rate of most of the formulation were more than 80% to 90%
Consolidation index % in 10hours study period [Figures2 and 3]. The higher
concentration of Carbapol 934 showed better sustained
It is one method for determining flow properties and also
called as carrs index of compressibility. It is indirectly related
Table4: Zero order and higuchi release for the following
to the relative flow rate, cohesiveness, and particle size. It is
formulations
simple, fast, and popular method of predicting powder flow
characteristic[Table3].[18] Time T % Cumulative amount of drug release
Formulation code
Tapped density - Bulk density
% consolidation index = 100 F1 F2 F3 F4 F5 F6
Tappedd density
1 1 20.66 17.60 19.50 13.19 20.95 15.80
Results and Discussion 2 1.414 35.80 21.32 31.92 20.21 32.93 31.15
3 1.732 45.11 37.90 39.55 27.10 43.40 44.40
4 2 51.23 46.20 47.42 36.37 56.35 47.50
The possible interactions between Rabeprazole sodium and 5 2.236 65.5 52.40 55.45 43.50 67.66 62
distinct polymers were investigated via FTIR studies. Results 6 2.449 70.4 63.30 62.35 54.60 73.835 65.55
proved that the drug was found to be compatible with excipients 7 2.645 80.51 69.80 69.87 61.40 82.321 74.5
as wave numbers are almost similar for pure drug as well as drug 8 2.828 85.36 80.30 74.35 69.65 83.651 80.80
excipients mixture. 9 3 89.40 88.15 81.65 77.40 88.162 85.40
10 3.162 93.62 92.35 88.38 84.60 91.425 87.85

All the formulated matrix tablets of Rabeprazole were mainly

prepared by using different polymers like HPMCE15,
Table5: First order drug release for following formulations
Carbopol934, sodium CMC either alone or in combination. The
matrix tablet mainly fabricated using wet granulation method. Time % ARA
As such all the formulated matrix tablets were of good quality F1 F2 F3 F4 F5 F6
respect to size, hardness, and drug content. 1 1.89 1.91 1.90 1.93 1.89 1.92
2 1.80 1.89 1.83 1.90 1.82 1.83
3 1.73 1.79 1.78 1.86 1.75 1.74
The hardness measured by Monsanto type hardness tester was
4 1.68 1.73 1.72 1.80 1.63 1.72
found within the range of 3 to 4.5g/cm2 and it was ideally suited 5 1.54 1.67 1.64 1.77 1.50 1.57
with requirement of matrix formulation[Table3]. 6 1.47 1.56 1.57 1.65 1.41 1.53
7 1.46 1.48 1.47 1.58 1.24 1.40
The weight variation study was performed on 20 individuals on 8 1.16 1.29 1.40 1.48 1.21 1.28
randomly selected samples from each batch; the weight uniformity 9 1.02 1.07 1.26 1.35 1.07 1.16
10 0.80 0.88 1.06 1.18 0.93 1.08
results of prepared matrix tablets indicate no significant difference
Journal of Pharmacy and Bioallied Sciences July-September 2014 Vol 6 Issue 3 183
 Khan, etal.: Evaluation of sustained release rabeprazole tablet

 Acknowledgement

The authors are humbly thankful to Mr. Durga Verma(Chairman) and

Mr. R. R. Aggarwal(Director) of Siddhartha Institute of Pharmacy,
 Dehradun, and D. S. Chauhan (Vicechancellor, Uttarakhand Technical
 University, Dehradun) for providing lab and library facilities.
&5)
&5


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