This document presents a dissertation thesis submitted for the degree of Master of Pharmacy in Pharmaceutics. The thesis investigates the formulation and evaluation of enteric coated tablets of Rabeprazole sodium, an anti-ulcer drug. Various studies were conducted including identification of the drug, evaluation of powder blends, drug-excipient compatibility, preparation of core tablets using different disintegrants, and coating of the tablets with an enteric polymer. The formulated tablets were then evaluated for parameters like hardness, thickness, friability, drug content, and disintegration time in acid and buffer media. The results of these evaluations are presented and discussed in the document.

1. “Formulation and Evaluation of Enteric Coated Tablet of
Rabeprazole Sodium’’
A Dissertation Thesis
Submitted to
RUHS, JAIPUR (RAJ)
Supervised By:
Mr. Awadh Kishor
Associate Professor
Dept. of Pharmaceutics
For the award of the degree
MASTER OF PHARMACY
(Pharmaceutics)
Presented By:
Mr. Ravindra Kumar Lohar
Enroll No.- 2012/1223
M. Pharm IV Sem.
Shrinathji Institute of Pharmacy, Nathdwara-313301 (Rajasthan)
RUHS, Jaipur
2018
1

2. CONTENTS
 INTRODUCTION
 LITERATURE REVIEW
 AIM AND OBJECTIVE
 MATERIAL AND METHODS
 RESULTS AND DISCUSSION
 CONCLUSION
 REFERENCES
 PUBLICATIONS
2

3. INTRODUCTION
ORAL DRUG DELIVERY
• Oral route is the most acceptable route of drug administration that
have been explored for the systemic delivery of drug via various
pharmaceutical products of different dosage form as powders, pills,
sachets, capsules or tablets.
• Convenient and safe way of drug administration.
• Compared to liquid dosage forms, tablets (and other solid dosage
forms) have general advantages in terms of the chemical, physical and
microbiological stability of the dosage form.
• The preparation procedure enables accurate dosing of the drug.
• Tablets are convenient to handle and can be prepared in a versatile
way with respect to their use and the delivery of the drug.
• Finally, tablets can be relatively cheaply mass produced, with robust
and quality-controlled production procedures giving an elegant
preparation of consistent quality.
3

4. MANUFACTURING PROCESS OF ENTERIC COATED TABLET
Dispensing
Shifting
Granulation
(Wet granulation)
Drying
Powder Blending
Tablet compression
Coating 4

5. ADDITIVES USED IN TABLETS
5
Diluents Lactose
Binders HPMC, Cellulose, Starch, PVPK30
Lubricants Talc, Magnesium Stearate
Glidants Colloidal Silicon Dioxide
Disintegrants Croscarmelose, Sodium Starch Glycolate
Coloring Agents Quinoline Yellow lake

6. ENTERIC COATED TABLETS
• A tablet that has a special outer covering designed to dissolve in the
small intestine. Once the enteric-coating is dissolved the tablet
disintegrates and the active ingredient can be absorbed by the patient.
An enteric coating is a barrier that controls the location of oral
medication in the digestive system where it is absorbed. The word
“Enteric” indicates small intestine; therefore enteric coatings prevent
release of medication before it reaches the small intestine.
ENTERIC COATING MATERIAL - PROPERTIES
1. Resistance and susceptibility
2. Stability and compatibility
3. Low cost and non-toxicity
4. Ease of application without specialized equipment.
6

7. ADVANTAGEs OF ENTERIC COATED TABLET
• Enteric coated Protect active pharmaceutical ingredients, from
the acidic environment of the stomach .
• To prevent gastric distress or nausea from a drug due to
irritation
• For the delivery of drugs that are optimally absorbed in the
small intestine to their primary absorption site in their most
concentrated form.
• To provide a delayed-release component for repeat action.
• Required for minimizing first pass metabolism of drugs.
7

8. COMPOSITION OF ENTERIC COATED TABLET
• Polymer
• Plasticizer
• Solvent
1. Water.
2. Isopropyl alcohol
3. Methylene chloride
4. Esters.
5. Chlorinated Hydrocarbons
• Colourant
• Additives
1.Pigments/Colorant
2.Opacifier
3.Anti-tacking agent
8

9. REVIEW OF LITERATURE
DRUG PROFILE
Name of the Ingredient Rabeprazole Sodium
IUPAC Name
2-[[[4-(3-methoxypropoxy)-3-methyl-2-
pyridinyl]-methyl]sulfinyl]-1H–benzimidazole.
Chemical Structure
Empirical Formula C18H20N3NaO3S
Molecular Weight 381.43 g/mol
Description White to slightly yellowish white powder.
Solubility
Very soluble in Water and Methanol, freely
soluble in Ethanol and Chloroform. 9

10. • Melting Point : 170-173 °C
• Half Life : 1-2 hours (In Plasma)
• Absorption : Absolute Bioavailability is 52 %
• Volume of Distribution : 160 Litre
• Protein Binding : 96.3 % (Bound to Human Plasma
Proteins).
INDICATION
• Gastric ulcer
• Peptic ulcer disease (PUD)
• Maintenance of healing of erosive or ulcerative GERD
• Healing of erosive and ulcerative GERD
• Healing of duodenal ulcers.
• Treatment of symptomatic GERD
• Treatment of pathological hyper secretory conditions 10

11. LITERATURE REVIEW
C. Murali Krishna Goud et al., (2017), Developed six formulations of Rabeprazole core
tablets were using mannitol as diluents, crospovidone and polyplasdone-XL as super
disintegrants, sodium carbonate anhydrous as stabilizer, magnesium stearate and talc as
lubricant and glidant in different proportions, and the prepared core tablets were coated
with enteric coating using hypromellose phthalate , myvacet, pigment blend yellow,
ethanol and purified water.
M. Kishore et al.,(2016) Formulated and evaluated the fabricated olsalazine sodium
enteric coated tablets in ulcerative colitis and also compare the In-vitro dissolution
profile of optimized Olsalazine sodium enteric coated tablets in the presence of β-
glycosidase at targeted colonic region.The present study was fabricated to observe the
drug release of Olsalazine sodium enteric coated tablets at targeted site specific colon
region.
Rakesh n. Tirpude et al.,(2016) Rabeprazole sodium is one of the most effective proton
pump inhibitors (PPIs) used in antiulcer therapy. Like most other PPIs, owing to its acid-
labile nature, the drug is formulated as enteric-coated dosage form. Conventional means
of producing delayed release multiparticulate dosage forms of PPIs require large
quantities of enteric polymer coatings.
11

12. • G Sridhar Babu et al., (2014), Formulated and evaluated the Delayed release tablets
of Rabeprazole sodium, an anti ulcer drug like peptic ulcer and duodenal ulcer.
Rabeprazole was class-I Proton pump inhibitor to gain FDA approval. Rabeprazole
sodium Delayed release tablets were prepared by Direct Compression method using
different excipients as well as with varying concentration of polymer proportions
using HPMC Phthalate 55 (HPMCP 55) as enteric coating material. All the excipients
are tested for compatibility with drug, which revealed that there was no physical and
chemical interaction occurred.
• Farha Amna Shaik et al., (2014), formulated and evaluated Rabeprazole Delayed
Release Enteric tablets comparable to the innovator product. Five formulations of
enteric coated tablets of Rabeprazole were developed by preparing core tablets using
mannitol as diluents and Crospovidone as super disintegrant in different proportions
and varying the compositions of sub coating and enteric coating using opadry white
and enteric yellow.
• Sourav Tribedi et al., (2013), Pantoprazole is a proton pump inhibitor, belongs to
group of benzimidazole, Pantoprazole sodium were prepared by direct compression
method using different concentration of, microcrystalline cellulose as filler, mannitol
and dicalcium phosphate as diluents, crosscarmellose sodium as disintegrating
agents, magnesium stearate and talc was used as a glidant and lubricant respectively.
12

13. AIM AND OBJECTIVE
• The aim of the present investigation was to Formulate And Evaluate
enteric coated tablets of Rabeprazole sodium by using different
Disintegration agent in different prorportion.
• Rabeprazole sodium is used in the treatment of acid related gastro
duodenal disorders by reducing gastric acid secretion. Proton pump
inhibitors are substituted benzimidazoles and all share a similar core
structure and mode of action, but differ in substituent groups.
• Delayed release dosage form is best formulations which are used for
drugs that are destroyed in the gastric fluids, or cause gastric
irritation, or are absorbed preferentially in the intestine. Such
preparations contain an alkaline core material comprising the active
substance, a separating layer and enteric coating layer.
13

14.  The present work was carried out to formulate enteric coated
tablets of Rabeprazole sodium and to evaluate the tablets for
various parameters. It was planned to carry out this work as
outlined below.
 Identification of Rabeprazole sodium by Infra-Red Spectroscopy.
 To Study the drug and excipient compatibility by FT-IR.
 To carry out the Pre-compression parameters of the powder
blend.
 To formulate enteric coated tablets of Rabeprazole sodium by
“Wet Granulation Method” using Sodium Starch Glycolate and
Croscarmellose as a disintegrant.
14
PLAN OF THE WORK

15.  Pre-compression Parameters
• Angle of repose
• Bulk density
• Tapped density
• Carr’s index
• Hausner’s ratio
 Evaluation of Compressed tablets
• Hardness
• Thickness
• Friability
• Weight variation
• Estimation of drug content
• Disintegration time
15
EVALUVATION PARAMETERS

16. Evaluation of Enteric Coated tablets
• Thickness
• Weight variation
• Percentage weight gain
• Estimation of drug content
• Disintegration time ( Acid and Buffer)
• In-vitro release studies
• Stability study
16

17. MATERIAL AND METHOD
List of Material
17
S. No. Ingredients Specification Reason for Inclusion
1 Rabeprazole sodium IP Anti Ulceration
2 Magnesium oxide light IP/BP Diluent
3 Colloidal silicon dioxide IP Lubricant
4 Microcrystalline cellulose IP/BP Diluent
5 Sodium starch glycolate IP/BP Disintegrant
6 P.V.P.K. 30 IP/BP Binder
7 Methylene chloride IP/BP Solvent
8 Talc IP/BP Lubricant
9 Colloidal silicon dioxide IP Glidant
10 Croscarmellose sodium USP Disintegrant
11 Ethyl cellulose IP/BP Coating Material
12 Methylene chloride IP/BP Solvent
13 Hydroxy propyl methyl cellulose IP/BP Enteric coating material
14 Cellulose acetate phthalate IP/BP Coating Material
15 Titanium dioxide IP/BP Filler
16 Purified talc IP/BP Pigment
17 Diethyl phthalate IP/BP Plastisizer
18 Colour iron oxide yellow In-House Colour
19 Isopropyl alcohol IP/BP Solvent
20 Methylene chloride IP/BP Solvent
21 Hydrochloric Acid IP/BP -

18. List of Equipment
18
S. No. Instrument / Equipment Make Process
1 Mass Mixer Hindco Granulation
2 Multimill Atin pharma Granulation
3 Fluid Bed Dryer Ace Eng. Granulation
4 Sifter Alpro Eng Granulation
5 Paste Preparation Vessel Alpro Eng. Granulation
6 Octagonal Blender Alpro Eng. Granulation
7 Rotary Machine No1 Hindco Compression
8 Weighing Machine Alfa systems Granulation
9 Weighing Machine Alfa systems Compression
10 Friability Machine RV Electronics Compression
11 Single Pan Balance Mettler Compression
12 D. T. Machine Wadegati Compression
13 Vernier Caliper Mitutoyo Compression
14 Hardness Tester Vishal Eng. Compression
15 Dust Extractor Cadmach Compression
16 I. R. Moisture Balance Rajdhani Granulation

19. METHODS
Preformulation studies
Identification
Evaluation of powder blend
• Angle of repose
• Bulk density and Tapped density
• Compressibility Index
• Hausner’s ratio
Drug excipients compatibility study
• Drug Excipients compatibility studies were carried out
by mixing the drug with various excipients in different
proportions. Studies were carried out in flint vials at
Accelerated conditions, 40°C ± 2°C / 75%RH ± 5 % RH.19

20. Result and Discussion
IDENTIFICATION BY INFRA-RED SPECTROPHOTOMETRY
Infra-Red of Rabeprazole Sodium ( Reference)
20

21. Infra-Red of Rabeprazole Sodium (Sample)
21

22. Flow properties of different formulations.
Flow Property Angle of Repose (degrees)
Excellent 25–30
Good 31–35
Fair - aid not needed 36–40
Passable - may hang up 41–45
Poor - must agitate, vibrate 46–55
Very poor 56–65
22
Blend Property
Formulations
B.D.
(gm/mL)
T.D.
(gm/mL)
C. I. (%) H. R.
Angle of
Repose
Property
F-I 0.580 0.679 14.58 1.275 42 Passable
F-II 0.612 0.750 18.40 1.225 37 Fair
F-III 0.658 0.810 18.76 1.231 36 Fair
F-IV 0.630 0.720 12.50 1.145 33 Good
F-V 0.667 0.730 8.630 1.094 29 Excellent
F-VI 0.648 0.780 16.92 1.203 38 Fair

23. 23
DRUG EXCIPIENTS COMPATIBILITY STUDY
S. No. Composition Initial Time
2nd
Week
4th
Week
1 Rabeprazole sodium White to off white powder
NCC NCC
2 Rabeprazole sodium + Magnesium oxide light White to off white powder
NCC NCC
3
Rabeprazole sodium + Colloidal silicon
dioxide
White to off white powder
NCC NCC
4
Rabeprazole sodium + Microcrystalline
cellulose
White to off white powder
NCC NCC
5
Rabeprazole sodium + Sodium starch
glycolate
White to off white powder
NCC NCC
6 Rabeprazole sodium + P.V.P.K. 30 White to off white powder
NCC NCC
7
Rabeprazole sodium + Cros carmellose
sodium
White to off white powder
NCC NCC
8 Rabeprazole sodium + Ethyle cellulose White to off white powder
NCC NCC
9
Rabeprazole sodium + Cellulose acetate
phthalate
White to off white powder
NCC NCC
10 Rabeprazole sodium + Diethyl phthalate White to off white powder
NCC NCC

24. Estimation of Rabeprazole sodium
y = 0.0274x + 0.0079
R² = 0.9999
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0 5 10 15 20 25 30
Absorbance
Concentration µ/mL
Calibration curve of Rabeprazole in
0.1N HCL
y = 0.0304x + 0.0009
R² = 0.9999
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0 5 10 15 20 25 30
Absorbance
Concentration µ/mL
Calibration curve Of Rabeprazole in
pH 6.8 Phosphate Buffer
24

25. 25
Evaluation of core tablets
Formulat
ion
Average
Weight
(mg)
Hardness
(kg/cm2)
Thickness
(mm)
Friability
(%)
Disintegration
Time (min)
Drug
Content
(%)
F-I 171 7.5 2.90 0.95 12 97.82
F-II 169 6.5 2.80 0.73 16 97.66
F-III 171 8.0 2.88 0.69 13 92.00
F-IV 170 6.5 2.95 0.48 10 95.48
F-V 170 5.0 2.80 0.35 7 98.80
F-VI 171 6.0 2.89 0.40 9 98.78

26. 26
EVALUATION OF ENTERIC COATED TABLETS
Formulation
Average
Weight
(mg)
Thickness
Change
(mm)
Percentage
Weight
Gain
(%)
Disintegration Time (min)
Drug
Content
(%)
Acid
Medium
(min)
Buffer
Medium
(min)
F-IV 192 3.10 12.94 47 - 96.84
F-V 192 3.15 12.94 120 14 100.10
F-VI 194 3.17 13.45 120 25 99.60
Market
Sample
198 3.48 - 120 19 96.91

27. 27
Invitro Drug Release Studies
Dissolution
Media
Sampling
Time
% Drug Release
F-IV F-V F-VI
Marketed
Sample
0.1 N HCl 2 hour 2.57± 0.67 2.08± 0.12 1.8± 0.12 1.7 ± 0.58
Phosphate
buffer, pH
6.8
10 mins 7.5 19.77 14.23 18.25
20 mins 32.54 75.28 52.22 73.32
30 mins 40.20 87.19 72.32 85.56
45 mins 44.62 95.98 86.21 89.72
60 mins 51.30 99.12 92.21 98.68

28. 28
STABILITY STUDIES
Parameters
40 oC ± 2 oC/ 75 % RH ± 5 %RH
Initial Period 1st Month 2nd Month 3rd Month
Description
Yellow
Coloured,
Circular
Yellow
Coloured,
Circular
Yellow
Coloured,
Circular
Yellow
Coloured,
Circular
Average weight
192 192 192 193
(mg)
Thickness (mm) 3.15 3.14 3.14 3.15
Disintegration
14 14.34 15 15.47
time (mins)
Assay (%) 100.10 99.96 99.56 99.06

29. CONCLUSION
• Formulation and evaluation of Enteric Coated tablets of
Rabeprazole sodium for the effective treatment of duodenal ulcer
was successfully carried out, by performing the preformulation
studies, formulation of Rabeprazole sodium enteric coated tablets,
evaluation parameters, in vitro drug release studies and stability
studies.
• The angle of repose of F-V formulation was found 29, which shows
excellent (25-30) flow property. F-I, F-II, F-III, F-IV and F-VI
formulations has angle of repose > 30. The compressibility index
of F-V was found 8.63 % which shows excellent flow character,
while F-I, F-II, F-III, F-IV and F-VI formulations found
compressibility index in range between 12.50 to 18.76 %. The
Hausner’s ratio of F-V formulation was found 1.094 which shows
excellent flowability, while F-I, F-II, F-III, F-IV and F-VI formulations
has > 1.11. The pre compression parameters of prepared powder
blend shows that F-V formulation has excellent flow property.
29

30. 30
• The drug excipients compatibility studies were carried out with aid of FT-IR
spectroscopic analysis of drug with excipients. There was no possible
molecular interaction between the drug and the excipients and comparable
with Reference spectra.The drug was compatible with excipients which
were further used in the formulation.
• Calibration curve was plotted for estimation using 0.1N HCl and Phosphate
buffer (pH 6.8). The results show good (R2 = 0.999) Correlation coefficient
with both the solvents.
• The drug content of F-V formulation uncoated tablets was found 98.80 %
which is within acceptable limits as per I.P.
• The disintegration time of selected formulation F-V (Coated) was found 14
minute (Mixed phosphate buffer, pH 6.8), while the disintegration time of
Market sample was found 19 minute in same buffer medium. The
disintegration time of F-VI formulation was found 25 minute, while F-IV
formulation failed in acidic medium (0.1 N HCL).
• The drug content of F-V formulation (coated) was found 100.10 %, which is
within acceptable limits as per I.P. . The In vitro drug release study revealed
that the drug released of FV formulation fairly matched with Marketed
sample. The drug release was found to be 99.12 % at 60 minute.

31. 31
• F-V formulation was kept for stability studies. No physical changes
were observed at the end of 1st, 2nd and 3rd month. Stability study
data showed no significance variation during stability studies. The
drug content of F-V formulation was found 99.06 % after 3rd month.
• From all the above observations the study concluded that the enteric
coated tablets of Rabeprazole sodium (F-V) formulation was better
one compared to the other formulations.

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32

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34. 34
PUBLICATIONS

35. 35

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37. 37

38. 38