International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 2 • Issue 1 • April – June 2009

Research Paper
Formulation and Evaluation of Gastro Retentive
Drug Delivery System for Ofloxacin
Dumpeti. Janardhan.2, Joginapally Sreekanth*2, V. Bharat1, P. Rama Subramaniyan1
1
Sri Ramachandra College of Pharmacy, Porur, Chennai
2
NATCO Pharma Ltd., Pharma Division, Kothur, Mahaboob Nagar (District), A.P, India.

ABSTRACT: The purpose of this investigation was to prepare a gastroretentive drug delivery system of Ofloxacin.
Ofloxacin is a fluoroquinolone antibacterial which acts by inhibiting the topoisomerase enzyme which is essential in the
reproduction of the bacterial DNA. It is highly soluble in acidic media and precipitates in alkaline media thereby losing its
solubility. Hence, a gastroretentive system was developed to enhance the bioavailability by retaining it in the acidic
environment of the stomach. Different formulations were formulated using various concentrations of hydroxy propyl methyl
cellulose, sodium carboxy methyl cellulose, sodium bicarbonate and citric acid. The formulations were evaluated for quality
control tests and all the physical parameters evaluated are within the acceptable limits of Indian Pharmacopoeia. All the
formulations were subjected to in-vitro dissolution studies and compared with the marketed formulation. The floating lag
time was below 15 seconds for all the formulations except F1 and F2. The floating duration was found to be more than
24 hours in all except F1, F2 and F10. Formulations F7 and F8 were used to study the effect of sodium bicarbonate and
formulations F9 and F10 for the effect of hardness on the drug release. Drug release kinetics was studied for prepared
formulations and optimized formulation F5 was found to follow zero order kinetics with r2 =0.993. The statistical analysis of
the parameters of dissolution data obtained before and after storage for 3 months at 25°C/ 60%RH and 40°C/75%RH
showed no significant change indicating the two dissolution profiles were similar.

KEYWORDS: Ofloxacin, gastroretentive, floating tablets, controlled release.

Introduction
Novel oral controlled dosage form that is retained in the
stomach for prolonged and predictable period is of major
interest among academic and industrial research groups.
One of the most feasible approaches for achieving
prolonged and predictable drug delivery profile in the GI
tract is to control gastric residence time (GRT). Dosage
form with prolonged GRT or gastro-retentive dosage form
(GRDF) provides an important option (S.S. Patel et al.,
2006).
Retention of drug delivery systems in the stomach
prolongs overall gastrointestinal transit time and improves
the oral bioavailability of the drugs that have site-specific
absorption from the stomach or the upper part of the small
intestine. So, different approaches have been proposed to
retain the drug in the stomach which includes bioadhesive
systems, swelling and expanding systems, floating
systems and delayed gastric emptying devices.
The principle of buoyant preparation offers a simple and
practical approach to achieve increased gastric residence
*For correspondence: Joginapally Sreekanth
E-mail: sreekanth@natcopharma.co.in
time for the dosage form and sustained drug release
(M.N. Gambhire et al., 2007).
Gastrointestinal retention depends on many factors
such as density of the dosage form, size of the dosage
form, fasting and fed condition, nature of the meal, sleep,
posture, etc. It also depends on a complicated and
unpredictable gastric emptying with migrating myoelectric
complex motility of the stomach (M.D. Chavanpatil et al.,
2006). It was suggested that compounding narrow
absorption window drugs in a unique dosage form with
gastroretentive properties would enable an extended
absorption phase of these drugs. Such a dosage form, after
oral administration, would be retained in the stomach and
release the drug in a sustained manner, so that the drug
could be supplied continuously to its absorption sites in the
upper gastrointestinal tract (M. Chavanpatil et al., 2005).
Ofloxacin exhibits pH dependant solubility. It is more
soluble in acidic pH and slightly soluble in neutral or
alkaline pH conditions (intestinal environment). In the
intestine, however, precipitation of the drug occurs, which
adversely affects the absorption in the lower sections of the

428
 Dumpeti Janardhan B et al. : Formulation and Evaluation of Gastro Retentive Drug Delivery System for Ofloxacin 429

intestine (M.D. Chavanpatil et al., 2006). There is a need Methods

for systems that reside in the stomach over a relatively
long period and release the active compound in a sustained
manner (M. Chavanpatil et al., 2005). Hence, a
gastroretentive dosage form of Ofloxacin, which releases
the drug in the stomach and upper intestinal tract was
developed.
Materials and Methods
Materials
Ofloxacin was received as a gift sample from NATCO
Pharma Ltd., Kothur, A.P., India. Hydroxy propyl methyl
cellulose (HPMC K4M and HPMC5cps) was purchased
from Colorcon Asia Pvt. Ltd. Sodium carboxy methyl
cellulose (JRS pharma), sodium bicarbonate, citric acid
anhydrous (Merck) and magnesium stearate (Ferro
industries Quimicas) polyvinyl pyrrolidone (ISP
Technologies) were used. Iso-propyl alcohol was
purchased from Merck.
Preparation of Ofloxacin gastroretentive tablets
Ofloxacin, HPMC K4 M, HPMC 5cps, and half the
quantities of previously powdered sodium bicarbonate, and
citric acid were weighed and passed through #40 mesh
(ASTM). Then all the above ingredients were mixed
geometrically for 5 min. The above blend was granulated
with binder solution containing PVP K30. The wet
granules were dried for 15 to 20 minutes at 50˚C to get
granules with an LOD less then 2%. The blend was then
passed through #30 mesh. Remaining quantities of sodium
carboxy methyl cellulose, sodium bicarbonate, and citric
acid previously powdered were mixed for 5 minutes with
the above blend. Magnesium stearate was weighed and
passed through #60 mesh, then mixed with above blend for
3 min in blender. Final blend was compressed into tablets
using 11 ± 0.1 mm flat round punches and corresponding
dies on rotary tablet compression machine (12 stationary,
Rimek, India). The composition of different formulations
is shown in Table 1.

Table 1. Composition of the formulations.

Name of Weight of excipients in mg

Excipients
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Intra granular
Ofloxacin 200 200 200 200 200 200 200 200 200 200
HPMC K4M 100 50 50 65 65 65 65 65 65 65
HPMC 5cps 150 200 125 90 90 86 100 80 90 90
Na CMC - - - - 8 10 8 8 8 8
NaHCO3 25 25 25 27.5 27.5 27.5 22.5 32.5 27.5 27.5
Citric acid
19 19 19 22.5 22.5 22.5 22.5 22.5 22.5 22.5
anhydrous
PVP K-30 40 40 20 25 25 25 25 25 25 25
Iso Propyl
q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s
Alcohol
Extra granular
Na CMC 12 12 12 16 8 10 8 8 8 8
NaHCO3 25 25 25 27.5 27.5 27.5 22.5 32.5 27.5 27.5
Citric acid
19 19 19 22.5 22.5 22.5 22.5 22.5 22.5 22.5
anhydrous
Magnesium
6 6 5 4 4 4 4 4 4 4
stearate
Tablet Weight 596 596 500 500 500 500 500 500 500 500
430 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 2 • Issue 1 • April - June 2009

packed in HDPE bottles and were kept in the humidity

In Vitro Buoyancy Studies
The in vitro buoyancy was determined by floating lag time,
as per the method described by Rosa. The tablets were
placed in a 100-mL beaker containing 0.1N HCl. The time
required for the tablet to rise to the surface and float was
determined as floating lag time (Rosa M et al., 1994).
In Vitro Dissolution Studies
The release rate of Ofloxacin (n = 6) was determined using
United States Pharmacopoeia (USP) 23 Dissolution
Testing Apparatus II (Paddle method). The dissolution test
was performed using 900 ml of 0.1N HCl, at 37 ± 0.5°C
and 50 rpm. A sample (5 ml) of the solution was
withdrawn from the dissolution apparatus at intervals of
0.5, 1, 1.5, 2, 3, 4, 6 and 8 hours and the samples were
replaced with fresh dissolution medium. The samples were
filtered through a 0.45-μ membrane filter and diluted to a
suitable concentration with 0.1N HCl. Absorbance of these
solutions was measured at 294nm using a UV/Visible
single-beam spectrophotometer (Agilent 8453, India).
Cumulative percentage drug release was calculated using
an equation obtained from a standard curve.
Stability
To assess the stability of the optimized formulation,
stability studies were conducted as per the ICH and WHO
guidelines (B. R. Mathews et al., 1999). Formulations were
chamber (Thermo lab, India) maintained at 25˚C/60%RH
and 40°C/75% RH for 3 months. At the end of studies,
samples were analyzed for the drug content, in vitro
dissolution, floating behavior and other physicochemical
parameters.
Results and Discussion
The prepared tablets were subjected to all the quality
control tests which showed (Table 2) that they were within
the official pharmacopoeial limits. The assay values were
within the range of 97 – 103%.
HPMC K4M was used as the rate retarding polymer
while HPMC 5cps was used because its low density helps
in floating of the tablet due to its swelling property which
decreases the tablet density in solution and gives a
buoyancy. Sodium carboxymethyl cellulose is used as a
channeling agent which guides water into the tablet by
forming pores due to its swelling property. Sodium
bicarbonate and citric acid anhydrous together are used as
the effervescent agent which gives a quick thrust to the
tablet to float immediately. The floating lag time (Fig 1.)
for all the formulations was found to be less than
15 seconds, except in F1 and F2. F1 failed to float while
F2 had taken 9 minutes to float.

Table 2. Quality Control Tests of the Formulations

Weight Hardness Thickness Friability Assay

S. No Formulations 2
Variation(mg) (Kg/cm ) (mm) (%) (%)

1 F1 596 +5.20 11.91+0.27 5.523+0.026 0.35 104.93

2 F2 596.85+3.12 14.14+0.56 5.331+0.027 0.44 101.48

3 F3 497.65+2.99 6.66+0.34 4.89+0.026 0.75 100.25

4 F4 499.3+4.03 7.63+0.22 5.302+0.029 0.245 103.5

5 F5 501+2.9 7.94+0.20 5.309+0.017 0.185 102.47

6 F6 499.3+3.23 6.80+0.26 4.774+0.027 0.398 97.83

7 F7 499.35+2.98 7.94+0.28 5.209+0.021 0.64 98.85

8 F8 498.1+3.69 7.76+0.40 5.222+0.024 0.367 101.16

9 F9 499.3+3.33 5.10+0.20 5.473+0.030 0.764 100.01

10 F10 499.45+3.84 11.29+0.18 4.815+0.021 0.198 99.35

 Dumpeti Janardhan B et al. : Formulation and Evaluation of Gastro Retentive Drug Delivery System for Ofloxacin 431

600

500

Time in Seconds
400

300

200

100

0
F2 F3 F4 F5 F6 F7 F8 F9 F10
Formulations

Fig 1. Floating Lag Times of the Formulations

The floating duration (Fig 2.) was found to be up to
24 hours in all formulations except F1, F2 and F10.
Incorporation of half the quantity of sodium carboxyl
methyl cellulose after the granulation along with sodium
bicarbonate and citric acid from F5 onwards was found to
improve the floating lag time and the drug release as well,
which might probably be due to the swelling and channel
zing property of sodium carboxy methyl cellulose. F10
might have failed to float due to extreme hardness of the
tablet.
The dissolution profiles of the formulations from F3 to
F9 are represented graphically in (Fig 3.) and the results
are shown in (Table 5).
The dissolution profile was compared (Fig 4.) with the
marketed product (Zanocin OD, Ranbaxy Labs, India) in
which the drug release was found to be 64% after 8 hours.
The drug release of formulation F5 was 89.275%, and the
similarity factor (F2) was found to be 75.2 (Table 6).
Modeling of the drug release was done using the best-
fit method. The release was plotted according to the Zero
order and Higuchi’s equations graphically and the
regression coefficient values were studied (Table 3).
Optimized formulation F5 was found to follow zero order
kinetics with r2 value of 0.993. This result shows that a
considerable amount of polymers as well as an
effervescent agent is required in both intra and extra
granulation for optimal drug release. The effect of sodium
bicarbonate on drug release was found to be evident since
lesser quantity (F7) decreased and higher quantity (F8)
increased the cumulative percentage of drug release at the
end of 8 hours. The effect of hardness was evident as well.
F9, with lesser hardness (4-6 Kg/cm2) showed an increase
in the drug release while F10 (10-12 Kg/cm2) floated for
only 2.5 hours, hence deleted from the drug release study.
The stability studies were carried out with the
optimized formulation (F5) for 3 months in two conditions
i.e. 25˚C/60% RH and 40˚C/75% RH. As per ICH
guidelines, the formulation were subjected to drug assay,
floating behavior and in vitro dissolution studies .The
statistical analysis of the parameters dissolution data
(Table 4), after storage for 3 months showed no significant
change indicating that the two dissolution profiles were
similar.
432 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 2 • Issue 1 • April - June 2009

30

25

Time in hours
20

15

10

0
F2 F3 F4 F5 F6 F7 F8 F9 F10
Formulations

Fig 2. Duration of floating for prepared formulations

100
90
80 F3
70
% Drug release

F4
60 F5
50 F6
40 F7
30 F8
20 F9
10
0
0 2 4 6 8 10
Time in Hours

Fig 3. Dissolution profile Formulations (F3 – F9)

Table 3. The Correlation Coefficient (r2) Values for Different Formulations

2
r
S. No Formulation
Zero order Higuchi’s
1 F3 0.901 0.782
2 F4 0.940 0.989
3 F5 0.993 0.943
4 F6 0.507 0.782
5 F7 0.923 0.993
6 F8 0.961 0.973
7 F9 0.925 0.990
 Dumpeti Janardhan B et al. : Formulation and Evaluation of Gastro Retentive Drug Delivery System for Ofloxacin 433

100
90
80

% Drug release
70
60
Zanocin OD 400 mg
50
F5
40
30
20
10
0
0 2 4 6 8 10
Time in Hours

Fig 4. Dissolution profile marketed formulation (Zanocin OD 400 mg) and Formulation F5 (Ofloxacin 200 mg)

Table 4. Dissolution Profiles of 3M Stability Samples at 25˚C/60% RH & 40˚C/75% RH

% Cumulative Drug Release

Time (hr) Initial 25˚C/60% RH 40˚C/75% RH
(0 months) (3 months)
0.5 9.95 9.23 8.96
1 16.05 15.78 13.65
1.5 21.54 22.68 20.93
2 25.67 27.92 23.04
3 39.06 39.69 38.18
4 51.51 50.11 49.33
6 70.49 71.24 69.22
8 89.27 87.88 87.96

Table 5. Percentage Cumulative Drug Release from the Formulations (F3 – F9)

Time
F3 F4 F5 F6 F7 F8 F9
(Hrs)
0.5 10.32 16.499 9.958 50.93 12.523 10.023 11.894

1 16.939 22.213 16.046 60.935 22.493 21.809 23.988

1.5 22.43 28.382 21.539 67.986 29.78 30.103 29.718

2 29.52 33.678 25.671 71.302 35.713 36.864 36.988
3 35.39 41.206 39.062 72.647 46.774 49.242 48.413

4 41.283 51.415 51.509 78.218 53.081 54.436 55.208

6 49.97 68.518 70.492 81.853 64.297 73.59 67.142
8 55.221 74.141 89.275 86.755 75.61 94.117 77.455
HEC1

434 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 2 • Issue 1 • April - June 2009

Table 6. Dissolution Profiles of Marketed Product (Zanocin OD 400 mg) and Formulation F5

Time in Hours Zanocin OD 400 mg Formulation (F5)

0 0 0
0.5 13.814 9.958
1 20.017 16.046
1.5 23.663 21.539
2 26.188 25.671
3 34.807 39.062
4 40.444 51.509
6 52.034 70.492
8 63.5 89.275

Conclusion bioadhesive gastroretentive drug delivery system for

The system using sodium carboxy methyl cellulose along
with sodium bicarbonate and citric acid added in equal
quantities before granulation and during lubrication
significantly increased the drug release from the
formulation. It is also evident that sodium bicarbonate
levels had a considerable effect on the drug release profile
along with the hardness levels as well.
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