Soumya Missula et al. Int. Res. J. Pharm.

2013, 4 (8)

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY

ISSN 2230 8407

www.irjponline.com
Research Article

FORMULATION AND IN VITRO EVALUATION OF OMEPRAZOLE FAST DISSOLVING TABLETS

Soumya Missula1*, Yarlagadda Ankamma Chowdary1, Gayathri Pedamallu1, Kondempudi Sai Krishna Mohan1,
Mellacheruvu Mohana krishna2
1
Department of Pharmaceutics, NRI College of Pharmacy, Pothavarappadu, Agiripalli Mandal, Vijayawada (A.P), India
2
St. Pauls College of Pharmacy, Hayath Nagar, Hyderabad, Ranga Reddy District, India
*Corresponding Author Email: [email protected]
Article Received on: 20/06/13 Revised on: 03/07/13 Approved for publication: 11/08/13
DOI: 10.7897/2230-8407.04833
IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com
All rights reserved.
ABSTRACT
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), Gastroesophageal reflux disease (GERD),
laryngopharyngeal reflux disease (LPR) and Zollinger-Ellison syndrome. The present study deals with the formulation of omeprazole fast dissolving tablets
utilising cross linked alginic acid and calcium silicate as super disintegrates and a total of 8 formulation batches were prepared. All the pre compression and
post compression parameters are studied and the results comply with in the limits. In vitro dissolution studies explained that the optimised F7 formulation with
super disintegrants Cross linked alginic acid at low ratio and Calcium silicate at high ratio showed a cumulative release of 99.6 % of drug at the end of 12
minutes and also exhibited first order kinetics with Higuchi mechanism of drug release.
Keywords: Omeprazole, Fast dissolving tablets, calcium silicate, cross linked alginic acid.

INTRODUCTION
The Centre for Drug Evaluation and Research (CDER), US
FDA1 defined fast dissolving tablets (FDT) as A solid
dosage form containing medicinal substances, which
disintegrate or dissolve rapidly, usually within a matter of
seconds, when placed upon the tongue.2 FDTs disintegrate
and / or dissolve instantaneously in the saliva without the use
of water. However some patients, particularly paediatrics and
geriatric patients have trouble in swallowing or chewing solid
dosage forms (conventional dosage forms). To avert the
impediments accompanying with dosage forms like the dry
syrups and effervescent tablets which require water for their
action whereas the chewable tablets have the problem of
bitter tasting or unpleasant taste of the drug and injections are
not preferred due to their intrusiveness. So, the development
of an appropriate dosage form is most desirable. The concept
of mouth dissolving drug delivery system emerged from the
desire to provide patient with more conventional means of
taking their medication. The elementary methodology in
development of FDT is the use of super disintegrants like
croscarmellose, sodium starch glycolate, cross linked alginic
acid etc, provide instantaneous disintegration of tablet after
putting on tongue, there by release the drug in saliva3,4.
Omeprazole is a proton pump inhibitor used in the treatment
of dyspepsia, peptic ulcer disease (PUD), Gastroesophageal
reflux disease (GERD), laryngopharyngeal reflux disease
(LPR) and Zollinger-Ellison syndrome. It is a selective and
irreversible proton pump inhibitor which suppresses the
gastric acid secretion by specific inhibition of hydrogenpotassium adenosine triphosphatase (H+-K+-ATPase) enzyme
system found at the secretary surface of the parietal cells. The
systemic bioavailability is 60 % for repeated doses and the
absorption is completed within 3-6 h5,6. The purpose of the
contemporary study is to formulate Omeprazole fast
dissolving tablets using super disintegrants cross linked
alginic acid and calcium silicate and study there in vitro
performance.

MATERIALS AND METHODS

Omeprazole is a gift sample obtained from In ventis Pharma
Pvt Ltd, Hyderabad, India Super disintegrates Cross linked
alginic acid and calcium silicate were acquired from Rhom
Pharma. Micro crystalline Cellulose, sodium saccharin,
magnesium stearate were obtained from Signet chemicals.
Aerosil was obtained from Aurobindo Pharma limited. All
the reagents used are of analytical grade.
Construction of Standard Calibration Curve for
Omeprazole
An accurately weighed 100 mg of omeprazole drug was
dissolved in 100 ml of 0.05 N HCl7 and used as primary stock
solution. From the primary stock, concentrations of 2, 4, 6, 8,
10 g / ml were prepared and the absorbance was measured
at 302 nm using UV-Visible spectrophotometer. A plot was
drawn taking concentration on x-axis and absorbance on yaxis and regression was determined as in Figure1.
Physical Evaluation of Powder blend
The powder blend was studied for angle of repose, bulk and
tapped densities, compressibility index and Hausners ratio8,9.
Determination of Angle of Repose
The flow property was determined by the angle of repose
which is the maximum angle that can be attained between the
free surfaces of a powder heap with its horizontal plane. The
formula for calculating angle of repose was:
= tan -1(h/r)
Where, h = height of the pile; r = radius of the pile

Values of less than 40 indicate reasonable flow property to

the powder and value greater than 50 indicates difficulty in
flow.
Determination of Bulk and Tapped Densities,
Compressibility Index and Hausners ratio
A fixed amount of powder (W) was placed in a measuring
cylinder and is allowed to fall under its own weight onto a
Page 168

Soumya Missula et al. Int. Res. J. Pharm. 2013, 4 (8)

hard surface from a 2.5 cm height at 2 sec time interval. The
tappings were continued until there were no void spaces and
the final volume was noted. The bulk density and tapped
density were calculated using the following formulas:
Bulk density = W / V0
Tapped density = W / Vf
Where, W = weight of the powder; V0 = initial volume; Vf = final volume.

Carrs Compressibility Index

It is measured from bulk and tapped densities. Calculated
using the formula,

and is expressed as kg/cm2. Three tablets for each

formulation were evaluated.
Friability
The tablets were subjected to combined effects of abrasion
and shock by placing them in a roche friabilator that revolves
at 25 rpm for about 4 minutes. Pre-weighed tablets (Wi) were
subjected to 100 revolutions and later de dusted with a muslin
cloth and the tablets weight (Wf) was noted. The friability (F)
can be calculated using
F=

Compressibility index, (CI) = 100 (V0 - Vf) / V0

Hausners ratio
It measured as the ratio of tapped density to the bulk density.
Hausners ratio = tapped density / bulk density

Method of Tablet Preparation

All the ingredients were accurately weighed and sieved
through mesh # 36. Except aerosil and talc all the others were
mixed geometrically. The blend was lubricated later with talc
and aerosil. Tablets of 200 mg were compressed using 9 mm
flat face circular punches which were fixed to the 16 station
single rotary tablet compression machine (Cadmach,
Ahmedabad, India). The prepared tablets were evaluated for
several post compression parameters like hardness, thickness,
weight variation, friability, drug content, disintegration time
and in vitro dissolution studies. Table 1 illustrates the list of
formulation batches.
Evaluation of Post Compression Parameters
Thickness10-12
The thickness of tablets was estimated using vernier callipers
expressed in mm.
Hardness
The formulated tablets were evaluated for hardness using a
Monsanto hardness tester. The force is applied diametrically

Wi - Wf
Wf

100

Weight Variation
Twenty tablets from each formulation were taken and the
average weight was noted. The individual weight was
compared with the average weight.
Wetting Time
A petri dish of internal diameter 6.5 cm was taken containing
10 ml of water with a soluble dye like eosin in which a tissue
paper folded twice and placed. On the top of it a tablet was
positioned and the time for complete wetting was noted.
Three trials were performed for each batch.
In vitro Disintegration Test
The in vitro disintegration was implemented in USP
disintegration apparatus. The set-up was done by employing
six tablets in each tube and the time necessary for the
complete disintegration with no palpable mass was noted in
seconds.
In vitro Dissolution Study
In vitro dissolution was done in USP dissolution type II
(paddle) apparatus with 900 ml of phosphate buffer pH 6.8 as
the medium at 100 rpm and the temperature was maintained
at 37 0.5C. 5 ml aliquots were withdrawn at specified time
intervals of 2, 4, 6, 8, 10 minutes and replaced with equal
amount of buffer to sustain sink conditions. The samples
were withdrawn and examined spectrophotometrically at 302
nm using UV-Visible spectrophotometer.

Table 1: List of Ingredients in Formulation Batches (F1-F8)

S. No
1
2
3
5
6
7
8

Ingredients
Omeprazole
Cross linked alginic acid
Calcium silicate
Sodium saccharin
Magnesium stearate
Aerosil
Microcrystalline cellulose
Total weight (mg)

F1 (mg)
20
10
2
3
4
161
200

F2 (mg)
20
20
2
3
4
151
200

F3 (mg)
20
40
2
3
4
131
200

F4 (mg)
20
80
2
3
4
91
200

F5 (mg)
20
10
40
2
3
4
121
200

F6 (mg)
20
20
80
2
3
4
71
200

F7 (mg)
20
10
80
2
3
4
81
200

F8 (mg)
20
20
40
2
3
4
111
200

Table 2: Results of Pre-Compression Parameters

Formulation
batch
F1
F2
F3
F4
F5
F6
F7
F8

Angle of repose ()
Mean S.D
28.5 0.85
26.5 0.50
29.7 0.35
28.9 0.85
26.6 0.55
30.5 0.15
31.5 0.65
29.9 0.45

Bulk density (gm/cc)

Tapped density (gm/cc)
Mean S.D
Mean S.D
0.55 0.06
0.65 0.06
0.45 0.06
0.67 0.05
0.51 0.03
0.71 0.08
0.52 0.04
0.65 0.04
0.49 0.05
0.70 0.06
0.52 0.02
0.66 0.05
0.56 0.08
0.63 0.07
0.55 0.05
0.62 0.06
*All values are calculated as Mean S.D

Compressibility index (%)

Mean S.D
15.5 0.52
17.5 0.42
19.8 0.1
16.4 0.55
15.6 0.06
16.9 0.60
15.8 0.25
18.8 0.15

Hausners ratio
Mean S.D
1.02 0.55
1.05 0.25
1.1 0.15
1.03 0.5
1.15 0.15
1.23 0.12
1.2 0.06
1.22 0.15

Page 169

Soumya Missula et al. Int. Res. J. Pharm. 2013, 4 (8)

Table 3: Results of Post-Compression Parameters
Formulation
batch
F1
F2
F3
F4
F5
F6
F7
F8

Thickness (mm)
Mean S.D
3.24 0.5
3.0 0.15
3.2 0.26
2.9 0.52
2.96 0.33
3.1 0.65
3.3 0.25
3.0 0.55

Hardness (kg/cm2)
Friability (%)
Weight variation
Mean S.D
Mean S.D
(mg) Mean S.D
3.8 0.65
0.54 0.5
202 0.5
3.74 0.55
0.75 0.15
205 0.6
3.95 0.5
0.64 0.5
195 0.5
3.7 0.15
0.44 0.25
198 0.2
3.9 0.55
0.77 0.6
196 0.6
4.2 0.05
0.65 0.55
204 0.8
4.0 0.35
0.62 0.4
200 0.5
3.95 0.15
0.59 0.15
1992 0.7
*All values are calculated as Mean S.D

Wetting time (sec)

Mean S.D
35 0.52
39 0.25
36 0.52
35 0.36
36 0.92
42 0.6
32 0.8
37 0.45

In vitro disintegration
(sec) Mean S.D
20 0.25
30 0.33
22 0.65
24 0.55
22 0.45
28 0.66
22 0.33
27 0.75

Table 4: Kinetic Values Obtained from in vitro-Release Data for Formulations F1-F8
Formulation
code
F1
F2
F3
F4
F5
F6
F7
F8

Zero order
R value
0.9715
0.9254
0.9156
0.8993
0.9602
0.9795
0.9525
0.9103

First order
R value
0.9856
0.9563
0.9936
0.9748
0.9686
0.9856
0.9758
0.9315

Figure 1: Standard Calibration Curve of Omeprazole

Higuchi
R value
0.9598
0.9755
0.9896
0.9963
0.9875
0.9845
0.9777
0.9658

R value
0.9558
0.9705
0.9567
0.9562
0.8965
0.9561
0.9687
0.9581

Korsmeyer Peppas
n value (release exponent)
0.4758
0.4561
0.4785
0.4963
0.5444
0.6654
0.5893
0.5677

Figure 2: Wetting Time Evaluation of Omeprazole FDTs

Figure 3: Comparison of in vitro-Disintegration Time and Wetting Time for Formulations F1-F8

Page 170

Soumya Missula et al. Int. Res. J. Pharm. 2013, 4 (8)

Figure 4: Cumulative % of Drug Released for Formulations F1-F8

RESULTS AND DISCUSSION

The fast dissolving omeprazole tablets were designed using
two super disintegrants Cross linked alginic acid and calcium
silicate. A total of 8 formulations were prepared and the
various quality control tests were adopted in tables 2 and 3.
There was no significant weight variation observed within
average weight and individual weight. The % friability of the
tablets was well within the tolerable range. The tablet
thickness ranged from 2.9 0.52 to 3.3 0.25. The hardness
of tablets ranged from 3.7 0.15 to 4.2 0.05. The %
friability ranged from 0.44 0.25 to 0.77 0.6. Wetting time
corresponds to the time taken for the tablet for the tablet to
disintegrate when kept motionless on the tongue. The wetting
time ranged from 32 0.25 to 42 0.6. The in vitro
disintegration time for the formulated tablets ranged from 20
0.25 to 30 0.33.
In vitro Dissolution Studies
All the 8 formulations were subjected to in-vitro dissolution
studies by using phosphate buffer as dissolution medium. InVitro release studies of all formulations were plotted and
shown in the Figure 4. Formulations F1, F2 contained low
and high concentrations of cross linked alginic acid showed
cumulative drug release of 45.5 % and 65.9 % respectively at
the end of 15 minutes. Formulation F3 and F4 contained low
and high concentrations of calcium silicate showed
cumulative drug release of 59.5 % and 78.5 % respectively at
the end of 15 minutes. Formulations F5, F6, F7 and F8
showed 85.9 %, 89.5 %, 99.6 %, 96.8 % respectively at the
end of 12 minutes. Out of all eight, F7 showed 99.6 % release
within 12 minutes. The cumulative % of drug release for all
formulations was shown in Figure 4. The drug release
followed first order kinetics for all formulation batches. (F1F8) on the basis of regression value (R value is greater for
first order). To ascertain the mechanism of drug release the
data was subjected to Higuchi and korsmeyer Peppas
equations and the kinetic date was depicted in Table 4.
Formulations F1- F8 showed Higuchi mechanism of drug
release. The optimised F7 formulation with super
disintegrants Cross linked alginic acid at low ratio and
Calcium silicate at high ratio exhibited first order kinetics
with Higuchi mechanism of drug release.

CONCLUSION
The use of super disintegrants cross linked alginic acid and
calcium silicate showed faster disintegration and dissolution
profile. Ideally F7 formulation was considered as optimized
which showed 99.6 % drug release at the end of 12 minutes.
All the formulations followed first order kinetics with higuchi
mechanism of drug release (F1-F8).
ACKNOWLEDGEMENT
The authors are thankful to NRI college of Pharmacy for providing adequate
lab facilities in the execution of the work.
REFERENCES
1. Seager H. Drug delivery products and the Zydis fast dissolving dosage
forms. J. Pharm. Pharmacol 1998; 50: 350-382. http://dx.doi.org/
10.1111/j.2042-7158.1998.tb06876.x
2. Chang RK, Guo X, Burnside BA and Cough RA. Fast dissolving tablets.
Pharm. Tech 2000; 24: 52-58.
3. Shastry CS, Srinath MS. Pharmaceutical approaches of taste masking
oral dosage forms, Ind. Drug 2004; 41(5): 253-257.
4. Bhushan SY, Sambhaji SP, Anant RP, Mahadik KR. New drug delivery
system for Elderly, Indian Drugs 2003; 37(7): 312-318.
5. www.medicinenet.com/omeprazole/article.html,
Accessed
date:
08/10/2011
6. Drug Bank, Canada (www.drugbank.ca), Drug Bank: Omeprazole
(DB00338). Available from: www.drugbank.ca/drugs/DB00338,
Accessed date: 05/10/2011
7. Macek J, Ptacek P, Klima J. Determination of omeprazole in human
plasma by high-performance liquid chromatography. J. of
Chromatography B 1997; 689: 239-243. http://dx.doi.org/10.1016/
S0378-4347(96)00283-6
8. Lakshmi PK, Jyothi G. Comparative evaluation of natural and synthetic
super disintegrants with newer super disintegrant Kyron T-314, Acta
Pharmaceutica Sciencia 2011; 53: 3544.
9. Chaulang G, Patil K, Ghodke D, Khan S, Yeole P. Preparation and
Characterization of Solid Dispersion Tablet of Furosemide with
Formulation Design and Evaluation of Mouth Dissolving Tablets
Omeprazole Magnesium by Using Super disintegrants, Res. J. Pharm
and Tech 2008; 1(4): 386-389.
10. Kuchekar BS, Badhan AC. Mouth dissolving tablets of salbutamol
sulphate ; a novel drug delivery system, Ind. Drugs 2004; 41(10): 592597.
11. Shanmungam S, Cendilkumar A. Rapidly disintegrating oral tablets of
valdecoxib, Ind. Drugs 2005; 42(10): 685-688.
12. Mishra DN. Rapidly disintegrating oral tablets of meloxicam by direct
compression method, Ind. Drugs 2006; 43(2): 117-12.
Cite this article as:
Soumya Missula, Yarlagadda Ankamma Chowdary, Gayathri Pedamallu,
Kondempudi Sai Krishna Mohan, Mellacheruvu Mohana krishna.
Formulation and in vitro evaluation of Omeprazole fast dissolving tablets.
Int. Res. J. Pharm. 2013; 4(8):168-171 http://dx.doi.org/10.7897/22308407.04833

Source of support: Nil, Conflict of interest: None Declared

Page 171