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Original Article FORMULATION AND EVALUATION OF DELAYED RELEASE PELLETS OF

RABEPRAZOLE SODIUM
*Muthukumaran M, Senthil Kumar K L, Ratnam B C
Padmavathi College of Pharmacy,
Peryanhali, Dharmapuri, Tamilnadu, India- 635205.

Abstract
The aim of the present investigation was to prepare delayed release i.e., enteric coated pellets of Rabeprazole
sodium by using hydroxypropyl methyl cellulose based sub coating and methacrylic acid copolymer based
enteric coating. The different batches of pellets were prepared by drug suspension layering method.
Comparative study of dissolution profile of final batch with market preparations was conducted and it was
concluded that final batch shown good similarity with market products. The results of the accelerated stability
of final formulation for three months revealed that storage conditions were not found any significant changes in
final formulation.

Key words: Rabeprazole sodium, Delayed release pellets, Enteric coating.

Introduction
Proton Pump Inhibitors (PPIs) are used in the treatment Such preparations contain an alkaline core material
of acid – related gastro – duodenal disorders by comprising the active substance, a separating layer
reducing gastric acid secretion1. Proton pump inhibitors and enteric coating layer3,4. The first aim of present
are substituted benzimidazoles and all share a similar work was to prepare Delayed release i.e., enteric
core structure and mode of action, but differ in coated pellets of Rabeprazole sodium by using
substituent groups. The type of substituents affects the Methacrylic acid copolymer in Fluid bed processor to
chemical properties of the compounds that directly prevent degradation in the stomach due to the acidic
influence their rates of reactions and therefore their environment or gastric enzymes and compare with the
stability in different media. The stability of PPIs in market sample.
aqueous media is a function of PH with an increased
rate of degradation as the PH decreases. Degradation Materials and Methods
of the Rabeprazole leads to a yellow or purple Rabeprazole Sodium (I.H.S) was a gift sample from
discoloration of the pellets, film layer or dissolution Lee Pharma, Hyderabad, India. Eudragit L30D-55 was
medium. Stability of Rabeprazole sodium also a gift sample from Evonik labs, Mumbai, India. Triethyl
decreases under moisture conditions. Exposure of citrate was gift sample from Signet chemical
Rabeprazole sodium to the acidic content of the corporation, Mumbai, India. Opadry clear was gift
stomach would lead to significant degradation of the sample from Colorco, USA. Polyplasdone XL, XL-10 gift
drug and hence, reduced bioavailability 2. Delayed sample from ISP, USA. Mannitol (Pearlitol SD200),
release dosage form is best formulations which are Sodium Carbonate (I.P), Talc (I.P) and all other
used for drugs that are destroyed in the gastric fluids, chemicals were of analytical grade.
or cause gastric irritation or are absorbed
preferentially in the intestine. Method
Preformulation studies
* Author for Correspondence: Preformulation studies were carried out for
Muthukumaran M, appropriate selection of excipients in view of
Padmavathi College of Pharmacy,
Rabeprazole Sodium modified release pellets.5,6,7
Peryanhali, Dharmapuri, Tamilnadu, India- 635205.
Email: [email protected] Micromeritic properties of Rabeprazole Sodium carried

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 183

were angle of repose, bulk density and tapped drug – coated pellets while the Glatt machine was set
density, Hausner’s ratio and drug excipients in running condition. After the coating was completed,
compatibility study for 4 weeks at accelerated the protective coating-covered pellets were again
conditions, 40±2oC /75%RH±5% RH. dried under warm air within the Glatt machine. Finally,
an enteric coating was prepared by mixing Eudragit
Formulation development of core pellets of L100-55 in a mixture of Isopropyl alcohol and
Rabeprazole sodium Methylen dichloride. This coating was placed into the
The drug suspension was prepared by mixing spray gun of the Glatt machine and sprayed onto the
Rabeprazole sodium, sodium carbonate, crosspovidone protective coating-covered pellets to form the
and Hydroxypropylmethyl cellulose in purified water. pharmaceutical pellets before final drying of the
The suspension was then placed into the spray gun granules to complete the process of making the enteric
system of Glatt fluid bed processor machine and coating-covered pellets.
sprayed onto the sugar core pellets while the Glatt
machine was set in running condition. This would allow Coating of pellets was done using Glatt fluid bed
the drug to be evenly coated onto the core pellets to processor machine. First fixed quantity (1Kg) pellets
form drug – coated spherical pellets. The drug – were put in the product chamber which was pre
coated pellets were dried under warm air within the adjusted at 50oC temperature for 5 – 10 minutes.
Glatt machine. The proportion of different batches of Various parameters like spray rate ( 8 to 25 gm/min),
Rabeprazole sodium core pellets are given in table 1. inlet air temperature (20 to 50oC), atomizing air
pressure (1 to 3 bar), % fludization (10 to 30%) and
Preparation of Coating solution of Opadry clear percent solids content 7% were adjusted and
To prevent interaction between Rabeprazole sodium optimized. After finishing of the coating pellets were
and enteric coating layer, seal coating of Rabeprazole dried at 40o C and at 10% fluidization. The coated
sodium pellets was done by Opadry clear until weight pellets were removed and evaluated by various
gain 8-10%. Coating solution was prepared by parameters.
dissolving Opadry clear in mixture of Iso Propyl
Alcohol (IPA) and Mehtylene Dichloride (MDC) under Evaluation parameters
constant stirring for 15-20 minutes by using propeller The prepared coated pellets were evaluated and
stirrer. compared with the marketed product.

Preparation of Coating solution of enteric coating Physical examination

solution A Micromeritic property of API is given in table 2.
Required quantities of solvents were weight in the Pellets were examined visually and observation was
beaker or other suitable vessel. Propeller stirrer was recorded and given in table 3. The Retention time of
used for preparation of coating solution. Propeller the major peak in the chromatogram of the sample
was kept in the center and as close to the bottom of preparation corresponds to that of the standard
the vessel as possible, stir the mixture of solvents to preparation. As obtained in the Assay.
form a vortex without entrapment of air in to the liquid.
After that required quantity of Eudragit L100-55 (for Moisture content
30% weight gain) was added in the water and kept The moisture content in the pellets was determined Karl
continuous stirring for 15-20 minutes. Fischer titrator

Coating of core pellets In vitro dissolution studies

A protective coating solution was prepared by mixing Dissolution studies of Rabeprazole sodium enteric
Opadry clear slowly in the solvent mixture of IPA and coated pellets were performed according to USP XXIII
MDC (60:40). This coating was then placed into the type II apparatus in 0.1N HCl for 2 hrs and in pH 8.0
spray gun of the Glatt machine and sprayed onto the sodium phosphate buffer 0.5% SLS for 30 min.

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Table 1: Formulation of different batches of Table 4: Comparison of Dissolution profiles of

Rabeprazole sodium core pellets Rabeprazole and coated pellets in pH8.0 buffer
Formulations

Market sample
Ingredients (quantities in gms)

(min)
Time
S.No
F1 F2 F3 F4 F5 F1 F2 F3 F4 F5

Rabeprazole sodium 285 285 285 285 285

Sodium carbonate 150 225 150 225 0
1 10 20.6 20 23.8 25 18 9
Hydroxy propyl methyl
80 80 80 80 80 2 20 58.9 54.0 62.8 40.2 45.6 30.2
cellulose
Polyplasdone INF 10 225 150 --- --- --- 3 30 84.36 76.0 86.2 65.8 69.8 40.6
Polyplasdone XL 10 --- --- 225 150 375
Sugar spheres 660 660 660 660 660
Talc 100 100 100 100 100 Figure 1:
Dissolution data’s of Rabeprazole sodium

Table 2: Micromeritic properties of API

Compressib
repose (θ)

ility Index

Hausner’s
Angle of
Sample

Tapped
density

density
(g/ml)

(g/ml)

ratio
Bulk

(%)

API 34 0.352 0.512 31.25 1.45

Table 3: Drug excipient compatibility study

(Physical observation)
The temperature was maintained at 37±0.5°C and the
Final description 1M/
Initial observation

(400C / 75%RH
Drug-Excipients

rotation speed was 100 rpm. The samples were

combination
Batch no.

D:E Ratio

withdrawn at 2hrs in acid and 10, 20, 30 min in buffer

7 days)

and analyzed HPLC (SHIMADZU). The in vitro data’s

are shown in figure 1. The table 4 and figure 2 shows
the data’s reveals the Comparison of Dissolution
profiles of Rabeprazole and coated pellets in pH 8.0
Off Off
1 RS -
White White
buffer.
RS+
2 1:10 White White Table 5: Stability studies data
Mannitol
RS + Temperature
3 Sodium 1:10 White White Time Test (%)
carbonate 40ºC / 75% RH
RS +
Assay 11.72
4 Titanium 1:0.25 White White
Initial
dioxide Acid resistance 99.75
RS + Off %DR 86.24
5 1:1 White
Opadry clear white
Fine Fine Assay 11.6
6 RS + Talc 1:0.25 1 month
white white Acid resistance 99.10
RS+
7 1:1 White White %DR 85.80
Crospovidone
RS + Assay 11.5
Hydroxy 2 months
8 1:1 White White Acid resistance 98.6
Propyl
Cellulose %DR 85.0

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Dissolution
Figure profile of selected
2: Dissolution stability
profile sample
of selected Evaluation parameters of the optimized batch of
stability sample Rabeprazole sodium
From the results of comparative study of dissolution
cumulative %drug

100 profile of final batch with market preparations. It was

80 Initial concluded that final formulation was shown good
release

60 1st month
similarity with market product.
40
20 2nd month Accelerated stability study of the optimized batch
0 From the results of the accelerated stability of the final
formulation for 3 months, it was concluded that storage
0 10 20 30 40 conditions were not found any significant changes in
Time (mins) final formulation dissolution profile with market sample.

Table 6: Comparison of Assay, Drug release

Conclusion
In coating process the enteric coating was done with
and Acid resistance of coated Pellets
the percentage build ups of 22, 24, 26, and 28 with
(Capsule) with market sample
8% sub coating. Acid resistance was failed up to 26%
Market
S.No Test % F1 F2 F3 F4 but at 28% build up acid resistance was passed. But
sample
for safer side, we coated up to 30% with 8% sub
1 Assay 11.58 11.64 11.72 11.70 11.72 coating. For optimizing coating process further trails
Drug were conducted with increasing sub coat and
2 84.36 76.09 86.24 65.82 69.82
dissolution decreasing enteric coating. From the above results, we
Acid found that F1, F2, F3 and F4 batches were passed in
3 98.68 99.08 99.75 93.7 98.2
resistance
assay and acid resistance tests. Batch F5 is not meeting
Assay- % labelled amount of Rabeprazole sodium.
the specification in terms of dissolution due to the
Drug Dissolution- % labelled amount of Rabeprazole
super-disintegrant particle size and lack stabilizing
sodium released in Buffer.
agent (Alkali). Based on results F2 formulation was
Acid resistance test-% labelled amount of Rabeprazole
found to be satisfactory with the market sample
sodium retained in acid.
dissolution profile. So finally F2 was found to be best
formula for formulation of Rabeprazole sodium
Stability Studies
delayed release pellet.
Stability studies were conducted at 40ºC / 75% RH for
about 3 months in stability chamber (thermo lab) 8.
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