80

Senthil Kumar S.K. et al. / International Journal of Biological & Pharmaceutical Research. 2011; 2(2): 80-84.

ISSN 0976 - 3651
2229 - 7480

International Journal of Biological
&
Pharmaceutical Research
Journal homepage: www.ijbpr.com


INVIVO EVALUATION OF GASTRO RETENTIVE FLOATING
MICROSPHERE CONTAINING REBEPRAZOLE SODIUM

*S.K. SENTHILKUMAR,
1
B.JAYAKAR,
2
S.KAVIMANI.

*Bharathi College of Pharmacy, Bharathi nagara, Mandya, Karnataka.
1
Vinayaka Missions College of Pharmacy, Salem, Tamilnadu.
2
College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health Sciences, Gorimedu, Indira Nagar,
Puducherry-605 006, India.

ABSTRACT
The present study was aimed to Invivo evaluation of gastro retentive floating microsphere containing Rabeprazole
sodium. Rabeprazole sodium microsphere was prepared by the solvent evaporation method using polymers HPMC, EC &
Chitosan. In vitro drug release studies were obtained for floating microsphere of RS showed good incorporation efficiency,
good buoyancy and prolonged drug release. The data obtained for floating microsphere of formulation 3 showed excellent
floatability. The higher polymer to drug ratio improved the entrapment efficiency, percentage yield, as well as buoyancy
percentage. Stability studies were performed for the prepared formulations and the results showed good stability. Peptic ulcer
occurs due to an imbalance between the aggressive (acid, pepsin and Helicobacter pylori) and the defensive (gastric mucus and
bicarbonate secretion, prostaglandins, innate resistance of the mucosal cells) factors. Number of drugs including proton pump
inhibitors, prostaglandins analogs, histamine receptor antagonists and cytoprotective agents are available for the treatment of
peptic ulcer. But most of these drugs produce several adverse reactions including toxicities and even may alter biochemical
mechanisms of the body upon chronic usage. It has been proposed that in ethanol induced ulcer model, ulcers are developed
due to accumulation of gastric acid and pepsin, which leads to auto-digestion of gastric mucosa. The Anti-ulcer property of RS
is evident from its significant reduction in free acidity, total acidity and ulcer index. Histopathological studies were also
confirming the potent activity for F3. It has been concluded that the best formulation of Rabeprazole sodium has significant and
extended anti-ulcer activity when compared with marketed drug.

Keywords: Rabeprazole sodium microsphere, Invivo, Invitro drug release, ulcer.

INTRODUCTION
Several approaches have been developed in order
to prolong the residence time of dosage forms in the
stomach (Mos AJ, 1993; Brahma N Singh et al., 2000).
Drugs that are easily absorbed from the gastrointestinal
tract (GIT) and have a short half-life are eliminated quickly
from the blood circulation, so they require frequent dosing.
Corresponding Author

S.K. Senthil Kumar
E-Mail:- senthilmekala@gmail.com


To avoid this drawback, the oral sustained-controlled
release formulations have been developed in an attempt to
release the drug slowly into the GIT and maintain an
effective drug concentration in the serum for longer period
of time. Oral administration is the most convenient and
preferred means of drug delivery to the systemic
circulation. Many attempts have been made to develop
sustained-release preparations with extended clinical
effects and reduced dosing frequency.


IJBPR
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Senthil Kumar S.K. et al. / International Journal of Biological & Pharmaceutical Research. 2011; 2(2): 80-84.


These systems allow prolonged residence time of
dosage forms in the stomach and the achievement of
constant plasma levels; however, it is necessary to analyze
the gastrointestinal transit behavior in humans to confirm
the suitability of the concept as far as the final design is
concerned. Gamma scintigraphy provides a noninvasive
means of acquiring information regarding the in vivo
performance of sophisticated oral dosage forms within the
gastrointestinal tract (Park K, 1988). The technique permits
formulations to be monitored none invasively under
normal physiological conditions. Pharmacoscintigraphic
evaluation provides direct insight into the in vivo fate of
the delivery system; moreover, it affords the opportunity to
examine the relationship between gastrointestinal transit
and drug absorption (Brown et al., 1998; Billa et al., 2000
Kedzierewicz et al., 1999; Davis et al., 1992).

To develop oral drug delivery systems, it is
necessary to optimize both the residence time of the system
within the gastrointestinal tract and the release rate of the
drug from the system. Various attempts have been made to
prolong the residence time of the dosage forms within the
stomach (Yuveraj Singh Tanwar et al., 2007; Deshpande et
al., 1996). The present study was aimed Invivo evaluation
of gastro retentive floating microsphere containing
Rabeprazole sodium. Rabeprazole sodium microsphere
was prepared by the solvent evaporation method using
polymers HPMC, EC & Chitosan.

Materials and methods
In vivo anti-Ulcer activity
Ulcer was induced by the oral administration of
absolute ethanol (5 ml/kg) to 24 h fasted Wistar male rats
(n =8), weighing 150-200g.Three groups of animal, each
containing eight animals were used. The first group
received control and the second group received pure drug
and the third group received the formulation 3.
Formulations (20 mg/kg of drug) were administered orally
1 hour before the administration of ethanol. After two
hours of ethanol administration, animals were sacrificed;
the stomachs were removed, opened along the greater
curvature, and examined for lesion measurements through
microscope (Plummer DI et al., 1985; Antonio et al., 2004;
Szabo et al., 1985). All the experimental protocols were
approved by IAEC (SVCP/IAEC/031-0064/2010-11) Sri
Vidyanikethan college of Pharmacy, Tirupati. Andhra
Pradesh.

Determination of free acidity and total acidity
The gastric content were centrifuged at 1000 rpm
for 10 min and 1ml of supernatant was diluted with 9 ml of
distilled water and titrated with 0.1 N Sodium hydroxide
run from micro burette using 3-4 drops of Topfers reagent
as indicator until canary yellow colour was observed. This
is correspondents to free acidity. Further 2-3 drops of
Phenolphthalein was added and titrated with 0.1 N Sodium
hydroxide until pink colour was restored. This is
correspondents to total acidity. The result shows the
significant decrease in total acid output and ulcer index.

Histopathological evaluation
The gastric tissue samples were fixed in neutral
buffered formalin for 24 hours. Section of tissue from
stomach was examined histopathologically to study the
ulcerogenic and/or anti-ulcerogenic activity of RS. The
processed tissue was embedded in paraffin blocks and
about 5-mcm thick section were cut and stained with
hemotoxylin and eosin. The slides were examined
microscopically for pathomorphological changes such as
congestion, hemorrhage, oedema and erosions using an
arbitory scale for the assessment of changes.


Results
In vivo studies:
Effect of RS on gastric ulcer induced by Ethanol
The RS showed significant anti-ulcer effect
against ulcers induced by Ethanol. In ethanol induced ulcer
model, RS at a dose of 20 mg/kg body weight showed
protective effect of 51.16% (4.20.25), where as RS
showed protection index of 67.67% (2.780.24) at a dose
of 20 mg/kg body weight. The results are shown in the
Table 1 and Figure 1.

Animals in the control group showed a significant
(P < 0.01) increase in the ulcer index and acid secretory
parameters like gastric volume, pH, free and total acidity
when compared with those of vehicle treated group.
Administration of RS produced significant (P < 0.01)
decrease in ulcer index, free and total acidity. The RS also
significantly reduced the gastric volume, total and free
acidity and increased the pH of the gastric fluid, proving its
antisecretory activity.

The anti-ulcer effect of RS was tested against
gastric lesions induced by ethanol. The experimental model
related to lesion pathogenesis with production of reactive
oxygen species reactive oxygen species are involved in the
pathogenesis of ethanol-induced gastric mucosal injury in
vivo. RS prevented the mucosal lesions induced by ethanol.
The gastric mucosal protection against ethanol can be
mediated through a number of mechanisms that include
enhancement of the gastric mucosal defence through
increase in mucus and/or bicarbonate production, reducing
the volume of gastric acid secretion or by simply
neutralizing the gastric acidity. RS may either reduce the
gastric acid secretion or enhance the barrier defence of the
mucosal wall. The results are shown in the Figure 2.
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Senthil Kumar S.K. et al. / International Journal of Biological & Pharmaceutical Research. 2011; 2(2): 80-84.



Histopathological studies suggest that the ethanol damage
to the gastrointestinal mucosa starts with micro vascular
injury, namely disruption of the vascular endothelium
resulting in increased vascular permeability, edema
formation and epithelial lifting. Hence histopathological
studies conformed, RS showed antiulcer effect in ethanol
induced gastric lesions. The results are shown in the
Figure 3.

Table-1. Anti-Ulcer Activity of Rabeprazole Sodium Microspheres

Treatment
Gastric
Volume
[ml]
pH
Free Acidity
[Eq/l]
Total Acidity
[Eq/l]
Ulcer index

% protection
Control
(Group-1)
8.6 1.2 3.28 0.01 26.3 1.04 55.0 1.3 8.6 1.03
-----
Marketed drug (RS)
20 mg/kg (Group-2)
6.3 0.04* 5.43 0.32* 11.90.32* 23.6 1.9* 4.2 0.25* 51.16 %
Best formulation
(RSM) 20 mg/kg
(Group-3)
5.4 0.21* 6.4 0.5* 9.2 0.52* 18.7 0.84* 2.780.24* 67.67 %
All value expressed as Mean SEM, *P<0.001 when compared to control

Figure-1. Plots Shows the Anti Ulcer Data for the Formulation F3 of Rabeprazole Sodium-HPMCK100m

G v pH FA TA U I
0
10
20
30
40
50
60
Group I
Group II
Group III

Figure 2. Histopathological Studies of Stomach

Normal control Disease control







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Senthil Kumar S.K. et al. / International Journal of Biological & Pharmaceutical Research. 2011; 2(2): 80-84.


Rabeprazole brand F 1










F2 F3














Figure 3. Gross Pathology of Stomach after Exposure to Ethanol
Normal control Disease control









Rabeprazole brand F 1









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F2 F3








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