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

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
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
absorption from the stomach or upper part of the small drug release.[1] The goal of any drug delivery system is to
intestine. Therefore different approaches have been proposed provide a therapeutic amount of drug to the proper site in
the body to achieve promptly and then maintain the desired
Access this article online drug concentration.[2] This deliberate control of drug release
Quick Response Code: is achieved in sustained release dosage form as it prolongs the
Website:
therapeutic effect by continuously releasing medication over an
www.jpbsonline.org 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
Khan, etal.: Evaluation of sustained release rabeprazole tablet

in oral controlled drug delivery to obtain a desirable drug release It has short biological halflife(1-2h)that requires frequent
profile, costeffectiveness, and broad regulatory acceptance.[4] daily dosing and therapeutic use in acidrelated diseases that
Matrix system are also favored because of their simplicity, patient necessitates its formulation into sustained release dosage
compliance than traditional drug delivery(TDS), which have form.[14] This study is an attempt to formulate Rabeprazole as
many drawbacks like repeated administration and fluctuation in sustained release matrix tablet for extending its release rate
blood concentration level. In this type of drug delivery system, for prolong period of time thus increasing the bioavailability.
the drug is homogeneously dispersed throughout the matrix
of crosslink of linear polymer chain.[5] It is assumed that from Materials and Methods
this type of drug delivery system, drug molecule come out from
matrix by dissolution and then diffusion through the polymer Materials
structure.[6] As the drug is released, the distance for diffusion
becomes greater and solid particles began to deplete. Most of Rabeprazole was received as a gift sample from Elder
the highly watersoluble drugs, if not formulated properly, may Pharmaceuticals Pvt Ltd, Dehradun (India). The polymer
readily release the drug at a faster rate, and are likely to produce HPMC E15, Carbopol 934, Sodium CMC was procured
toxic concentration.[6] Hydrophilic polymers have become from Elder Pharmaceuticals Pvt Ltd, Dehradun(India). Talc,
product of choice as an important ingredient for formulating Magnesium stearate was from S.D. Fine Chem. Ltd. Mumbai.
sustained release formulations of highly water soluble drugs.[7] All the chemicals were of analytical grade.
As the dissolution medium or biological fluid penetrates the
dosage form, the polymer swells and drug molecules begin to Methods
move out of the system by diffusion at a rate determined by the
nature and composition of the polymer as well as formulation Identification of pure drugs
technology.[8]
Identification of Rabeprazole was examined by FTIR and
Sustained release matrix tablets prepared by wet granulation compared with the reference spectrum of drug.
technique using microcrystallineethyl cellulose polymer and
Bees wax showed good sustaining drug release concluding Method used to estimate rabeprazole sodium
that sustained release tablet could be successfully combined
with accurate control and prolongation of the drug release The drug Rabeprazole Sodium was dissolved in phosphate
patterns.[9,10] buffer 7.2 to obtain 10 g/ml solutions. Further diluted with
the same buffer and scanned for maximum absorbance(max)
Chemically Rabeprazole is designated as RS)-2([4(3methox in a double beam UVVIS Spectrophotometer, between the UV
ypropoxy)3methylpyridin2yl] methylsulfinyl)1Hbenzo[d] ranges from 200 to 400nm against phosphate buffer pH7.2
imidazole with molecular formula C18H21N3O3S. It is the as blank; and max is found to be 287nm.
member of substituted benzimidazoles which inhibits the final
step in gastric secretion. Prepration of calibration curve

In vitro and animal studies have demonstrated that rabeprazole Rabeprazole in water
is a more potent inhibitor of H+, K(+)ATPase and acid secretion
than omeprazole, and is a more rapid inhibitor of proton Accurately 25mg of Rabeprazole was taken in a 100ml
pumps than omeprazole, lansoprazole, or pantoprazole. This volumetric flask. Sufficient amount of water was added to make
probably reflects rabeprazoles faster activation in the parietal up the mark(stock solution). 10ml of the volume was made up
cell canaliculus.[11] to the mark with water using the standard solution 1ml, 2ml,
4ml, 6ml, 8ml, 10ml that was withdrawn individually and
It inhibits the final transport of hydrogen ions(via exchange in each case the volume was made up to 10ml. The absorbance
with potassium ions) into the gastric lumen. Since the H+, of these solution were measured spectrophotometrically at
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 


$EVRUEDQFH


hour of administration.[12] Elimination of rabeprazole occurs \ [
 5 
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) &RQFHQWUDWLRQ

isoenzyme, CYP2C19.[13] Figure1: Standard curve of rabeprazole

Journal of Pharmacy and Bioallied Sciences July-September 2014 Vol 6 Issue 3 181
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 20 tablets were selected at random and weighed accurately;
sieve no.80 separately. Accurately weighed amount of polymers the average weight of the tablet was calculated. Then the
and excipients were thoroughly mixed in glass mortar pestle. The deviation of individual weight from the drug weight was
granules were prepared by wet granulation technique and passed calculated[Table3].[15]
them to sieve no.20 and dried in hot air oven at 45C. The
granules were then mixed properly with magnesium stearate, Determination of thickness of tablets
talc and punched with the help of automatic punching machine
to a desired hardness, shape, and size[Table2]. The individual crown to crown thickness of ten tablets was
determined using slide calipers for each batch[Table3].[16]
Determination of hardness of tablet
Measurement of the density of formulation
Randomly sampled 5 tablets in each batch of formulation
were used for the determination of hardness with the help of The approach densities of the tablet were calculated from
Monsanto type hardness[Table3].[15] the volumes and masses in triplicate. The volumes(v) of the
cylindrical tablets were calculated from their heights(h) and
Determination of friability radius(r) are both determined with micrometer gauze using
the mathematical equation for a cylinder[Table3].[17]
Roche friabilator is used in which approx. 6 gm of dedusted
V = r2h
Table1: Data for standard curve of rabeprazole in distilled Determination of drug content in tablets
water
Conc. (Microgm/ml) Absorbance 3 tablets from each batch were selected randomly and transferred
1 0.091 to a 100ml volumetric flask were, filled up with 0.1N HCL.
2 0.15 Kept it for 48 hours then took 1ml from each of volumetric flask
4 0.289
6 0.417
was transferred to the test tubes samples were then filtered,
8 0.535 suitable diluted and analyzed spectrophotometrically at a
10 0.674 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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