Sunitha et.

al / IJIPSR / 2 (8), 2014, 1658-1665

RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

International Journal of Innovative

Pharmaceutical Sciences and Research
www.ijipsr.com
FORMULATION AND EVALUATION OF PANTOPRAZOLE
SODIUM ENTERIC COATED PELLETS
1

J.Sunitha*, 2C.Sowmya, 3B.Srinath, 4K.Thejeswini, 5P.Venkatesh

Raghavendra institute of pharmaceutical education and research, Anantapur, AP, INDIA

Abstract
A peptic ulcer is a hole in the gut lining of the stomach, duodenum, or esophagus. An ulcer occurs when the
lining of these organs is corroded by the acidic digestive juices which are secreted by the stomach cells.
Peptic ulcer disease is common, affecting millions of Americans yearly. Pantoprazole sodium is proton
pump inhibitor and used as an antiulcer agent. The study was undertaken with an aim to formulate
pantoprazole sodium enteric coated pellets. The present study was focused to formulate delayed release
capsule by MUPS Technique. Sieve analysis was the essential step before coating. Because uniform sized
pellets undergo effective coating. To avoid degradation of drug in upper part of GIT, above developed
pellets are further coated with enteric coating polymer. Methacrylic acid copolymer dispersion was coated
18, 20, and 30 % for first three trials. Above developed formulation were evaluated for invitro dissolution
.Dissolution was carried out in USP 32 apparatus II (paddle) using 1000 ml of 0.1 N HCl for 2 hrs, coated
pellets slowly release (not more than 10%) and after that in 1000 ml of pH 6.8 phosphate buffer rapid
dissolution of pellets were observed. drug show 78.2 % release after 45 min. and hence F5 trial was satisfy
the dissolution criteria.
Key words: Pantoprazole, Pellets, MUPS.

Corresponding Author:
J.Sunitha
Department of Pharmaceutics
Raghavendra institute of pharmaceutical education and research,
Anantapur, AP, INDIA
Email: jallasunitha87@gmail.com
Mobile: +91-8142209642
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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

INTRODUCTION
A peptic ulcer is a hole in the gut lining of the stomach, duodenum, or esophagus. A peptic ulcer
of the stomach is called a gastric ulcer; of the duodenum, a duodenal ulcer; and of the esophagus,
an esophageal ulcer. An ulcer occurs when the lining of these organs is corroded by the acidic
digestive juices which are secreted by the stomach cells. Peptic ulcer disease is common,
affecting millions of Americans yearly. Controlled drug delivery is delivery of drug at a rate or at
a location determined by needs of body or disease state over a specified period of time [1, 2].
The most important reason for the wide acceptance of multiple unit products is the rapid increase
in popularity of oral controlled release dosage forms, Controlled release oral solid dosage forms
are usually intended either for delivery of the drug at a specific site within the gastrointestinal
tract or to sustain the action of drugs over an extended period of time [3]. Different theories have
been postulated related to the mechanism of formation and growth of pellets. As the
conventional granulation, the most thoroughly studied, most classified pelletisation process,
which involves a rotating drum, a pan or a disc, has been divided into three consequtive regions:
nucleation, transition and ball growth [4]. Pelletization by extrusion and spheronization
involves first making the extrudes from the powder material and then converting the extrudes
into beads using the spheronizer. The powder material could be any kind of powder (drug
powder, ayurvedic powder, food ingredient powder, detergent powder, nuclear powder etc).
Beads as fine as 0.6mm can be made [5]. The wurster machine employs a cylindrical product
container with a perforated plate. Inside the container is a second cylinder (coating partition)
with is raised slightly above the perforated plate, centered in the plate below this partition is a
spray nozzle used to dispense the coating solution [6]. Enteric coatings are those which remain
intact in the stomach, but will dissolve and release the contents once it reaches the small
intestine. Their prime intension is to delay the release of drugs which are inactivated by the
stomach contents or may cause nausea or bleeding by irritation of gastric mucosa [7].
Formulation aids or excipients are added to pharmaceutical dosage forms mainly to produce
satisfactory delivery of the drug to the intended site, to impart favorable characteristics to the
dosage form and to facilitate the manufacture of the product. Since pellets are intended to be
administered orally, the excipients used in the pellet dosage forms are typically the same as those
used in tablet or capsule formulations.

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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

MATERIAL
Propranolol is obtained from Cipla Pvt. Ltd., Mumbai. Micro crystalline cellulose is obtained
from Loba Chemical Pvt. Ltd., Mumbai. Cross povidone, HPMC, Sodium carbonate, Magneiusm
Stearate and Talc are obtained from Astra Zeneca Pvt. Ltd., Bangalore. Zein, Triethyl citrate,
titanium dioxide and Eudragut are obtained from Sangam Laboratories Ltd.Tarapur.

METHOD
Table 1: Ingredient used for Formulation of Tablet
Ingredient used

Mg / Tab

Pantoprazole sodium Sesquihydrate

194.24

MCC (Avicel pH101)

208.96

Crosspovidone

40

HPMC

4.8

Sodium carbonate anhydrous

28

Magnesium stearate

Talc

Purified water

q.s
Total

486

Core pellets was prepared by extrusion and spheronization method.The required quantity of
pantoprazole sodium was weighted and sifted through sieve 30, Microcrystalline cellulose,
disintigrant (crosspovidone or crosscarmelose sodium), sodium carbonate, hydroxyl propyl
methyl cellulose were weighted accurately and sifted through sieve, and blend was prepared.
Antitacking agents talc and magnesium steareate were passed through sieve 60 Hydroxyl propyl
methyl cellulose was dissolved in purified water. And It is used as granulating fluid for
granulation. All ingredients mixed properly and HPMC solution was added the prepared wet
mass was passed through extruder; cylindrical shaped extrudates were formed and then keep in
to spheronizer for rounding the extrudates. Extrudate rotate in spheronizer at different RPM 75,
100, and 125 for 10 min. checked the LOD of wet pellets. Fluid bed dryer was used for drying
the pellets at a temperature below 40 0C.

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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

Table: 2 Composition Sub coating and Enteric coating in the formulation trials
Formulations

F1

F2

F3

F4

F5

F6A

F7

Zein

1.24

1.24

1.24

1.24

1.87

1.87

1.87

Eudragit L100 55

0.26

0.26

0.26

0.26

0.38

0.38

0.38

Iso Propyl Alcohol

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Purified Water

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

ENTERIC COATING
Eudragit L100 55

8.36

10.45

12.54

14.63

15.76

17.86

19.96

Tri Ethyl Citrate

0.83

1.04

1.25

1.46

1.58

1.79

Purified Talc

1.26

1.58

1.90

2.21

2.39

2.7

3.03

Titanium Dioxide

1.64

2.06

2.47

2.88

3.11

3.52

3.94

Iso Propyl Alcohol

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Sub coating solution was prepared by dispersing Zein and Eudragit,clear slowly in the solvent
mixture of IPA and water (90:10) & stirred for 30 min. Tablets were loaded into coating pan and
warmed up to the temperature of 35 40C. The solution was kept under continuous stirring
during the coating process. The coating was continued till target weight build up was achieved.
After target build up was achieved, the pan speed was reduced and spraying of solution was
stopped then the coated tablets were dried at the temperature of 35C40C for 15 minutes. Sub
coating 1% and 1.5 %, build ups of sub coat given to tablets and coating was continued until
target build up was achieved and collected into a container. Enteric coating solution was
prepared by slowly dispersing Eudragit in IPA and after getting clear add Triethyl citrate and in
another beaker take talc and Titanium Dioxide homogenize for 30 minutes.Then add this
Homogenised solution to Eudragit solution and stirring carried out for 30-45 min. The dispersion
was sifted through muslin cloth and collected into a stainless steel vessel. The sub coated tablets
were loaded into coating pan and the tablets were warmed till up to the temperature of 38C
40C.The dispersion was kept under continuous stirring, during the coating process. The coating
was continued till target weight build up was achieved. After target build up was achieved the
pan speed was reduced and spraying of enteric coating dispersion was stopped and the tablets
were warmed at the temperature of 38C 40C for one hour .
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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

RESULT & DISCUSSION

Standard plot of Propranolol HCL in PH 6.8 phosphate buffer
100 mg of propranolol HCL was accurately weighed and dissolve into 100 ml volumetric flask
containing pH 6.8 buffer solution to get a concentration of (1000 g/ml) i.e. stock solution-I.
from this 1 ml was withdrawn and and diluted to 100 ml with pH 6.8 phosphate buffer, to get a
concentration of (10 g/ml) ie.stock solution-II.
Calibration curve in ph 6.8 phosphate buffer solution:
From the stock solution-II, 1,2,3,4,5,6,7,8and 9ml sample were withdrawn and volume was made
up to the mark with pH 6.8 phosphate buffer. This solution gives 1,2,3,4,5,6,7,8,and 9 g/ml
concentration of Propranolol Hcl. The absorbance of these solution measured in UV at 291 nm
using pH 6.8 phosphate buffer as blank.
Table 3: Calibration of Propranolol Hcl in
pH 6.8 phosphate buffer

Concentration
(mcg/ml)
0

10

0.131

20

0.272

30

0.414

40

0.552

50

0.692

Sl. No

Fig 1: Standard plot for Propranolol Hcl

pH 6.8 phosphate buffer

Absorbance
0

DRUG AND EXCEPIENT COMPATIBILITY STUDIES

Drug- excipient compatibility studies lay the foundation for designing a chemically stable
formulation for clinical and commercial development. drug excipient compatibility studies are
conducted during preformulation to select the most appropriate excipients. It is clear from the
below observation of the below values of characteristics absorption

bands for different

functional groups and bonds of the drug and its polymer that is most of the cases there is no
appreciable change in the position of the bands. Even if negligible deviation exist, its due to the
different types of the polymers used for the study.

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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

Table 4: Result of FTIR Spectra of Propranolol Hcl Pure Drug and Polymers
Final observation
Name of the Excipient

Ratio

Pantoprazole

Initial
White to off
white
white
White to off
white

40C/75% RH
nd
2 week 4th week
White to White to
off white off white
white
white
White to White to
off white off white

conclusion

Compatible

Pantoprazole : Cross povidone

1 :1

Compatible

Pantoprazole : HPMC

1:1

Pantoprazole : MCC

1:5

white

white

white

Compatible

Pantoprazole :Sodium Carbonate

Anhydrous

1:1

white

white

white

Compatible

Pantoprazole :Titanium dioxide

5:1

white

white

white

Compatible

Pantoprazole :Tri ethyl Citrate

5:1

white

white

white

Compatible

Pantoprazole :Magnessium stearate

20:1

white

Off
white

Brown

In Compatible

Pantoprazole :Talc

1:1

white

yellow

yellow

Pantoprazole : Eudragit L100 5S

1:1

white

white

white

Compatible

Pantoprazole :Zein

1:1

yellow

yellow

yellow

Compatible

Compatible

In compatible

Dimensions
Size of the pellets in the range of 1.28 -1.40 mm determine by Using vernier caliper
Hardness
Hardness of pellets in the range of 9 -17 N determined by Dr.Schieuniger hardness tester
Invitro dissolution test
Table No. 5 The percentage of drug release from pellets in each capsule in Different Trials
Percentage of drug release in different trials

Dissolution
Media

Sampli
ng time

F1

F2

0.1 N HCl

2 hr

41.48%

38.64%

10 min

74.35%

68.79%

20 min

94.86%

88.68%

30 min

98.94%

96.75%

45 min

99.47%

98.87%

6.8 pH
phosphate
buffer

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F3
28.45
%
62.48
%
81.68
%
93.65
%
99.45
%

F4

F5

F6

F7

24.4 %

13.7 %

8.5%

5.8%

46.53
%
61.48
%
74.03
%

24.67
%
42.49
%
58.35
%

92.68
%

78.46
%

64.67
%
78.48
%
88.24
%

78.67%

98.78
%

94.47
%

August Issue

50.7%

86.38%

USP
Specification
NMT 10%
drug release

NLT 75%
drug release

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RESEARCH ARTICLE
Department of Pharmaceutics

ISSN (online) 2347-2154

Fig. 2: Comparative drug release profile From F1 toF7

CONCLUSION
Pantoprazole sodium is proton pump inhibitor and used as an antiulcer agent. The study was
undertaken with an aim to formulate pantoprazole sodium enteric coated pellets.
Before going to develop the formulation a detail product literature review was carried out to
know about the MUPS and type of dosage form available in market.
The present study was focused to formulate delayed release capsule by MUPS Technique.
In preliminary trials various formulation combinations and parameters such as spheronization
speed, time of spheronization, amount of granulating fluid, quantity of MCC, were responsible to
produce spherical and smooth surface pellets. Shape, surface area, uniform sized pellets undergo
efficient coating. Microcrystalline cellulose has been found to be effective diluent in the
extrusion and spheronization method. With increase in quantity of MCC the surface of pellets
more plastic and easily adopt spheroid shape and also needed more amount of granulating fluid.
28% w/w content MCC was found to be optimum to produce the pellets of required
characteristics. Similarly pellets were prepared with varying amount of granulating liquid. Higer
amount of granulating liqid result in harder pellets that could not obey the dissolution criteria
specified in USP. 300 ml of granulating fluid was found to sufficient for pellets preparation.
Average pellets size was determined by sieve analysis and found to be 1680-1200 microns
(ASTM sieve no. 12-16). Sieve analysis was the essential step before coating. Because uniform
sized pellets undergo effective coating. Drug turns brown when come in contact with moisture
therefore pellets were dried and undergo seal coating as early as possible. To avoid barrier
diffusion and moisture penetration seal coating was applied 5 % by using HPMC. FBD was used
to dry the pellets. To avoid degradation of drug in upper part of GIT, above developed pellets are
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Department of Pharmaceutics

ISSN (online) 2347-2154

further coated with enteric coating polymer. Coating was performed in Fluid bed coater. But still
pellets were fully and partially dispersed in 0.1N HCl. Then acryl ezee blend was used as coating
suspension (20 % coating suspension) weight gain 30, 32 % for remaining two trials. 32 %
Increasing coat thickness by using Eudragit suspension was satisfied the USP dissolution criteria.
Above developed formulation were evaluated for invitro dissolution .Dissolution was carried out
in USP 32 apparatus II (paddle) using 1000 ml of 0.1 N HCl for 2 hrs, coated pellets slowly
release (not more than 10%) and after that in 1000 ml of pH 6.8 phosphate buffer rapid
dissolution of pellets were observed. drug show 78.2 % release after 45 min. and hence F5 trial
was satisfy the dissolution criteria

REFERENCE
1. Bramankar D M and Jaiswal S B , Biopharmaceutics and Pharmacokinetics A Treatise,
1ed,Vallabh prakashan, Delhi , p.335,337 (1995).
2. Vyas S P and Khar R K , Controlled drug delivery system : Concepts andadvances,1ed,
Vallabh Prakashan, New Delhi , p.167(2002).
3. Bramankar D M and Jaiswal S B , Biopharmaceutics and Pharmacokinetics A Treatise,
1ed,Vallabh prakashan, Delhi , p.335,337 (1995).
4. Lachman L and Lieberman H A , Kaing J L, The Theory and Practice of Industrial
Pharmacy,3rded, Bombay ,Varghese publishing house p.

(1987).

5. Gennrao R A , Controlled release drug delivery system ,The science and

Practice of pharmacy, remingtan 20th ed, vol 1, and p.903-930.
6. Vyas S. P. And Khar R K , Controlled drug delivery: Concepts and Advances,1 ed
,Vallabh Prakashan, New Delhi , p.15 (2002).
7. Chien Y.W, Rate controlled drug delivery system: controlled release Vs Sustained
Release, med.prog.tech, 1989 (15) P.21-46.

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