ISSN (P): 2349-8242 Comparitive in-vitro drug release ... · Coating will protect the drug from the surroundings with a view to improve its stability. Coating can modify the drug

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The Pharma Innovation Journal 2018; 7(10): 447-455

ISSN (E): 2277- 7695

ISSN (P): 2349-8242

NAAS Rating: 5.03

TPI 2018; 7(10): 447-455

© 2018 TPI

www.thepharmajournal.com

Received: 21-08-2018

Accepted: 24-09-2018

Sofia Konain

Deccan School of Pharmacy,

Dar-us-salam, Aghapura,

Nampally, Hyderabad,

Telangana, India

Sirisha Mittapally




Telangana, India

Correspondence

Sofia Konain




Telangana, India

Comparitive in-vitro drug release study of enteric

coated rabeprazole tablets using synthetic and

natural polymers

Sofia Konain and Sirisha Mittapally

Abstract Enteric coated tablets are tablets which are coated with polymers to prevent the release of drug in the

stomach and allow the drug release in the small intestine. Enteric Coating is used to protect the active

Pharmaceutical Ingredient from the acidic environment and to prevent gastric distress caused from a drug

due to irritation. The purpose of this research work is formulation of enteric coated tablets using

Synthetic and Natural polymers and comparing their release studies. Nine formulations of Rabeprazole

core tablets were formulated from which F9 was found to be the optimized one. Then the optimized core

tablet was coated with 4 different polymers- Eudragit L100, HPMC, Sodium Alginate and Shellac with

different concentrations F1 to F16. Compatibility studies were performed which showed no interaction.

The dissolution study shows that Eudragit L100 has 100% drug release and the natural polymers Sodium

Alginate and Shellac were also equally effective. Therefore, it can be concluded based on the

experimental studies that the natural polymers can also be a good alternative to synthetic polymers. Out

of the two Natural Polymers, Shellac exhibited good performance compared to Sodium Alginate.

Keywords: enteric coating, rabeprazole, synthetic polymers, natural polymers, eudragit l100, sodium

alginate, shellac, HPMC, anti-ulcer drug

Introduction

Solid dosage form

A solid dosage form is drug delivery system that includes tablets, capsules, sachets and pills as

well as a bulk or unit-dose powders and granules. Oral route of drug administration is widely

acceptable, and drugs administered orally as solid dosage form represents the preferred class of

products. Over 90% of drugs formulated to produce systemic effects are produced as solid

dosage forms

Coatings

Coating is a process by which an essentially dry, outer layer of coating material is applied to

the surface of a dosage form to confer specific benefits that broadly ranges from facilitating

product identification to modifying drug release from the dosage form [4].

Reasons for tablet coating

The core contains a material which has a bitter taste in the mouth or has an unpleasant

odour.

Coating will protect the drug from the surroundings with a view to improve its stability.

Coating can modify the drug release profile, e.g., enteric coating, osmotic pump, pulsatile

delivery [6].

Enteric coating

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. The enteric coated

polymers remain unionize at low pH, and therefore remain insoluble. But as the pH increases

in the GIT, the acidic functional groups are capable of ionization, and the polymer swells or

becomes soluble in the intestinal fluid. Materials used for enteric coatings include CAP, CAT,

PVAP and HPMCP, fatty acids, waxes, shellac, plastics and plant fibers.

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The Pharma Innovation Journal

Polymers for enteric coating

Polymers are substance containing a large number of

structural units joined by the same type of linkage.

These substances often form into a chain-like structure starch,

cellulose, and rubber all possess, polymeric properties.

Classification of polymers

Natural polymers

Shellac

Shellac is a polymer used in coating applications to provide

various functional properties. It can be used in film coatings

to achieve enteric applications, aesthetic and immediate-

release properties, taste masking, and seal coating. Shellac is a

natural and versatile polymer used for coating applications.

Sodium alginate

Sodium alginate is the sodium salt form of alginic acid and

gum mainly extracted from the cell walls of brown algae, with

chelating activity. In tablet formulations, sodium alginate may

be used as both a binder and disinter grant.

Cellulose esters

Cellulose esters have been widely used in the industry. CAP

has the disadvantage of dissolving only above the pH 6, and

possibly delaying the absorption of drugs. HPMCP-50,

55,55S these are derived from Hydroxy propyl cellulose,

these polymers dissolves at low pH (5 to 5.5) than CAP or

acrylic co-polymers.

Polyvinyl derivatives polyvinyl acetate phthalate (PVAP)

Polyvinyl Derivatives Polyvinyl acetate phthalate (PVAP)

Polyvinyl acetate phthalate (PVAP) is manufactured by the

esterification of a partially hydrolyzed polyvinyl acetate with

pthalic anhydride. This polymer is similar to HP-55 in

stability and pH-dependent solubility. It is supply as ready-to-

use or ready-to-disperse enteric systems.

Syntehtic Polymers

Polymethacrylates (Methacrylic acid/ethyl acrylate)

Two forms of commercially available enteric acrylic resins

are Eudragit L and Eudragit S both resins produce film that

are resistant to gastric fluid. Eudragit L and Eudragit S are

soluble in intestinal fluid at pH 6 to 7 respectively. Eudragit L

is available as an organic solution, solid, or aqueous

dispersion. Eudragit S is available as an organic solution and

solid [4].

Rabeprazole is a proton pump inhibitor that suppresses gastric

acid production in the stomach. Rabeprazole's mechanism of

action involves the permanent inhibition of proton pumps in

the stomach, which are responsible for gastric acid

production. Rabeprazole belongs to a class of antisecretory

compounds that do not exhibit anticholinergic or histamine

H2-receptor antagonist properties but suppress gastric acid

secretion by inhibiting the gastric H+/K+ATPase at the

secretory surface of the gastric parietal cell.

2. Materials and Methods

Materials

Table 1: List of Ingredients

S. No. Materials Category Suppliers

1 Rabeprazole Proton Pump Inhibitors Reddy Laboratories, Hyderabad

2 Micro Crystalline Cellulose Diluent S.D.Fine Chem.Ltd,Mumbai,India

3 Cross Providone Superdisintegrant S.D.Fine Chem.Ltd,Mumbai,India

4 Crosscarmellose Sodium Superdisintegrant Myl Chem.Ltd,Mumbai,India

5 Sodium Starch Glycolate Superdisintegrant Myl Chem.Ltd,Mumbai,India

6 Magnesium Stearate Lubricant S.D.Fine Chem.Ltd,Mumbai,India

7 Starch Binder Essel Fine Chem. Mumbai

8 Lactose Monohydrate Filler Essel Fine Chem. Mumbai

9 Aerosil Glidant Myl Chem.Ltd,Mumbai,India

10 Eudragit L 100 (%W/W) Film Former S.D.Fine Chem.Ltd,Mumbai,India

11 Hpmc Hydrophilic Polymer S.D.Fine Chem.Ltd,Mumbai,India

12 Sodium Alginate Release-Retarding Agent S.D.Fine Chem.Ltd,Mumbai,India

13 Shellac Polymer Myl Chem.Ltd,Mumbai,India

14 Acetone Solvent Myl Chem.Ltd,Mumbai,India

Experimental Methods

Determination of λmax of Rabeprazole

Standard Stock solution: 100 mg of Rabeprazole was

dissolved in 100 ml of pH 6.8 phosphate buffer (1000 μg/ml)

Scanning: From the stock solution 10μg/ml was prepared in

methanol and UV scan was taken between 200 to 400 nm.

The absorption maximum was found to be 282 nm and was

used for the further analytical studies.

Calibration curve of rabeprazole in 0.1N HCL

From the standard stock solution (1000 μg/ml), appropriate

aliquot were transferred to series of 10 ml volumetric flasks

and made up to 10 ml with 0.1 N HCL, so as to get

concentration of 4, 8, 12,16 and 20 μg/ml. the absorbance of

the solution were measured at 282nm. This procedure was

performed in triplicate to validate calibration curve. A

calibration graph was plotted.

Preparation of 6.8pH phosphate buffer

Dissolve 28.80g of disodium hydrogen phosphate and 11.45g

of potassium dihydrogen phosphate in sufficient water to

produce 1000ml.

Calibration curve of rabeprazole in 6.8pH phosphate

buffer

From the standard stock solution (1000 μg/ml), appropriate

aliquot were transferred to series of 10 ml volumetric flasks

and made up to 10 ml with 6.8pH phosphate buffer so as to

get concentration of 4, 8, 12,16 and 20 μg/ml. the absorbance

of the solution were measured at 282nm. This procedure was

performed in triplicate to validate calibration curve. A

calibration graph was plotted.

Formulation development of rabeprazole enteric coated

tablets

An ideal mixture of powder is directly punched into tablets

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weighing about 200 mg containing 20 mg of Rabeprazole, using rotary tablet compression machine.

Table 2: Compilation of Rabeprazole core Tablets

Formulation(mg) F1 F2 F3 F4 F5 F6 F7 F8 F9

Rabeprazole 20 20 20 20 20 20 20 20 20

Sodium starch glycolate 5% 7.5% 10%

Cross povidone 5% 7.5% 10%

Cross caramellose sodium 5% 7.5% 10%

Starch 4% 4% 4% 4% 4% 4% 4% 4% 4%

Lactose monohydrate Qs Qs Qs Qs Qs Qs Qs Qs Qs

Aerosil 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5%

Magnesium stearate 2% 2% 2% 2% 2% 2% 2% 2% 2%

Total weight 200 200 200 200 200 200 200 200 200

Table 3(a): Enteric Coating Formulation

Ingredients EC1 EC2 EC3 EC4 EC5 EC6 EC7 EC8

Eudragit L 100 (%W/W) 2% 4% 6% 8% - - - -

HPMC - - - - 2% 4% 6% 8%

Sodium alginate - - - - - - - -

Shellac - - - - - - - -

Acetone QS QS QS QS QS QS QS QS

Table 3(b): Enteric coating formulation

Ingredients EC9 EC10 EC11 EC12 EC13 EC14 EC15 EC16

Eudragit L 100 (%W/W) - - - - - - - -

HPMC - - - - - - - -

Sodium alginate 2% 4% 6% 8% - - - -

Shellac - - - - 2% 4% 6% 8%

Acetone QS QS QS QS QS QS QS QS

Rabeprazole enteric coated tablets

Rabeprazole enteric coated tablets were prepared by direct

compression technique using different excipients as well as

with varying concentrations disintegrants.

Manufacturing process

1. Co-sift Rabeprazole, Starch and Disintegrant through

sieve # 30.

2. Sift Lactose monohydrate through sieve # 30.

3. Sift the Step 1 and Step 2 materials through # 30 mesh.

4. Load the step 3 materials into blender and mix for 30

mins.

5. Sift Aerosil through sieve # 40 along with a portion of

prelubricated blend.

6. Load the step 5 material to the blender and mix for 5

mins.

7. Compress the lubricated blend of step no. 8 into tablets.

Preparation of enteric coating solution:

1. Disperse coating polymer in Acetone under stirring to

prepare clear solution.

2. Add plasticizer and talc to the step no. 10 solution.

3. Add color which is pre-sifted and add to the step no.11

Spray coating solutions on tablets using spray gun in coating

pan. Warm the enteric-coated tablets in coating pan at 50°C ±

5°C for 20 -30 mins.

3. Evaluation

Pre-compression Characteristics

Angle of Repose

Angle of repose is used to determine the flow properties of

powders, pellets or granules. Angle of repose is the maximum

angle possible between the surface of a pile of the blend and

the horizontal plane. Fixed funnel method was employed. A

funnel that was secured with its tip at a given height above the

graph paper was placed on a flat horizontal surface. Granules

were carefully poured through the funnel until the apex of the

conical pile just touches the tip of the funnel. The radius and

height of the pile were then measured. The angle of repose ()

for samples were calculated using the following equation [1].

tan θ =height of the heap

radius of the heap

Bulk Density

Bulk density of a compound varies substantially with the

method of crystallization, milling or formulation. Bulk

density is determined by pouring pre-sieved granules into a

graduated cylinder via a large funnel and measure the volume

and weight [1].

Bulk Density =Weight of Granules

Bulk Volume of Granules

Tapped Density

Tapped density is determined by placing a graduated cylinder

containing a known mass of granules and mechanical tapper

apparatus, which is operated for a fixed number of taps until

the powder bed volume has reached a minimum volume.

Using the weight of the granules in the cylinder and this

minimum volume, the tapped density may be computed [1].

Tapped Density =Weight of Granules

Tapped Volume of Granules

Compressibility Index (CI)

Compressibility index is measured by using the values of bulk

density and tapped density. The following equation is used to

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find the Carr’s index.

CI =Tapped Density − Bulk Density

Tapped× 100

Hausner’s ratio

The ratio of tapped density to bulk density of powders is

called the Hausner’s ratio. It is calculated by the following

equation1.

Hausner′s Ratio = Tapped Density

Bulk Density

Post-Compression Characteristics

Weight Variation

The USP weight variation test will be run by weighing 20

tablets individually, calculating the average weight, and

comparing the individual tablet weights to the average [2].

Weight Variation =Weight of Tablet − Average Weight

Weight of Tablet − Average Weight× 100

Weight variation should not be more than 7.5%.

Table 4: Weight Variation Tolerances for Uncoated Tablets

S. No. Average Weight of

Tablets (mg)

Maximum Percentage

Difference Allowed

1 80 or less 10

2 80 to 250 7.5

3 More than 250 5

Thickness and diameter

The thickness of a tablet will be the only dimensional variable

related to the process. 10 tablets were measured for their

thickness and diameter with Vernier calipers, Thickness

Gauge. Average thickness and diameter were calculated3.

Hardness

Hardness of the tablets will be determined by Varian

Hardness Tester and the hardness should be found within the

range of 3.5-5.5 kg/cm². A tablet is placed between the anvils

and the crushing strength which causes the tablet to break is

recorded4.

Friability

The friability of tablets will be determined by Electrolab EF-

2, Friabillator. 20 tablets were taken and weighed. After

weighing the tablets were placed in the Electrolab EF-2,

Friabillator and subjected to the combined effects of abrasion

and shock by utilizing a plastic chamber that revolves at 25

rpm, dropping the tablets from a distance of six inches with

each revolution. After operation the tablets were de-dusted

and reweighed5. Friability is determined by using below

equation:

F = 100(1 −W0

Wt⁄ )

Where, W0= weight of tablets before friability test.

Wt= weight of tablets after friability test.

Disintegration test

Disintegration testing of coated dosage forms was carried out

in the six tablets basket rack USP disintegration apparatus.

One tablet was introduced into each tube of the basket rack

assembly of the disintegration apparatus without disc. The

assembly was positioned in the beaker containing 900ml of

Water. The disintegration time of each tablet was recorded [5].

Dissolution

Procedure: Drug release studies were carried out using a USP

type II dissolution test apparatus at 50rpm for 2hours in

900ml 0.1N HCl previously maintained at 37 °C ± 0.5 °C. 5ml

of sample was taken and analyzed.

After 2hrs replaced with pH 6.8 and tested for drug release for

12hrs at same temperature and rotation speed. 5ml of aliquots

were withdrawn at pre-determined time intervals and an equal

amount of the medium will be replaced to maintain sink

conditions. The aliquots were diluted suitably, and the amount

of drug released will be determined by U.V method.

4. Results And Discussions

Ultraviolet Visible (Uv-Visible) Spectroscopy

Drug sample showed wavelength of maximum absorption (λ-

max) 282 nm

Fig 1: λ-max of Rabeprazole

Standard Graph of Rabeprazole (0.1 N Hcl):

The standard graph of RABEPRAZOLE has shown good

linearity with R2 values 0.998 in 0.1 N Hcl and which

suggests that it obeys the “Beer-Lambert’s law”.

Table 5: Standard Graph Readings

Concentration Absorbance at 282nm

0 0

2 0.202

4 0.395

6 0.558

8 0.745

10 0.912

Fig 2: Calibration Curve for Rabeprazole in 0.1N Hcl at 282nm

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Standard Graph of Rabeprazole in 6.8pH phosphate

buffer:

The standard graph of RABEPRAZOLE has shown good

linearity with R2 values 0.999 and, which suggests that it

obeys the “Beer-Lambert’s law”.

Table 6: Standard Graph Readings in 6.8 PH Buffer

Concentration Absorbance

0 0

2 0.156

4 0.290

6 0.419

8 0.580

10 0.718

Fig 3: Calibration Curve for Rabeprazole in 6.8 pH Phosphate

Buffer at 28

Drug - excipients compatibility studies By Ft-Ir

Fig 4: FTIR Spectra of Rabeprazole

Fig 5: FTIR of rabeprazole optimized formulation

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Evaluation of pre compression parameters for enteric coated tablets of rabeprazole

Table 7: Precompression data of rabeprazole core tablet

Formulations Angle of Repose (θ) Loose Bulk Density (g/ml) Tapped Bulk Density (g/ml) %Compressibility Hausner’s ratio

F1 27.520.15 0.44±0.04 0.50 ± 0.04 12.00±0.6 1.13±0.04

F2 28.400.11 0.44±0.05 0.50 ± 0.1 12.00±0.4 1.13±0.02

F3 28.310.13 0.43±0.045 0.51± 0.04 15.68±0.8 1.18±0.08

F4 25.340.13 0.45±0.044 0.52± 0.01 13.46±0.1 1.15±0.06

F5 26.100.12 0.43±0.045 0.51 ± 0.04 15.68±0.6 1.18±0.08

F6 29.670.19 0.42±0.044 0.50 ± 0.09 16.00±0.8 1.19±0.09

F7 28.33±0.2 0.47±0.02 0.53±0.05 11.32±0.8 1.12±0.09

F8 25.66±0.14 0.45±0.03 0.56±0.05 19.64±0.05 1.24±0.05

F9 28.540.19 0.51±0.045 0.59 ± 0.04 13.55±0.07 1.15±0.06

Angle of repose

Angle of repose values for batch F1 –F9 falls within the range

of 25-30, and the flow property was found to be good.

Bulk and Tapped Density

The bulk density value for the formulated blend was found to

be within the range of 0.4 to 0.5 gm/ml, where as the tapped

density was found to be within the range of around 0.5 to

0.6gm/ml.

Compressibility index

The percentage compressibility for the batch F1- F9 was

found in to be within the range 17 and the flow property was

found to be excellent.

Hausner’s ratio

The Hausner’s ratio value for the batch F1 –F9 falls within

the range of 1.11-1.26 and found to have good flow property.

Table 8: Post Compression Parameters of Core Tablet

Formulations Weight variation (mg) Hardness (Kg/cm2 ) Thickness (mm) Friability (%) Assay % (W/W)

F1 200 ± 0.04 3.40 ± 0.2 2.5 ± 0.01 0.43 ± 0.11 100.3± 0.21

F2 202 ± 0.02 3.62 ± 0.1 2.2 ± 0.04 0.45 ± 0.12 100.1± 0.16

F3 201 ± 0.04 3.50 ± 0.2 2.8 ± 0.01 0.49 ± 0.12 100.8± 0.16

F4 199 ± 0.05 3.43 ± 0.3 2.3 ± 0.04 0.50 ± 0.11 99.0± 0.19

F5 200 ± 0.05 3.44 ± 0.3 2.2 ± 0.03 0.31 ± 0.12 98.9± 0.19

F6 202 ± 0.02 3.47 ± 0.2 2.1 ± 0.04 0.32 ± 0.12 99.4± 0.21

F7 201 ± 0.02 3.49 ± 0.1 2.6 ± 0.06 0.19 ± 0.11 100.6± 0.16

F8 199 ± 0.04 3.50 ± 0.2 2.2 ± 0.03 0.16 ± 0.12 100.2± 0.16

F9 201 ± 0.03 3.50 ± 0.1 2.0 ± 0.02 0.29 ± 0.12 99.5± 0.16

Hardness

The Hardness of the formulated batch F1 to F9 was

maintained in the range 3.4 to 3.6 Kg/cm2.

Percentage friability

The percentage friability for the formulated batches F1 to F9

was found to be within the range i.e, NMT 1% w/w.

Assay

For the entire formulated batch from F1-F9 the assay value

was found to be within the limits of 90-110% w/w.

Weight variation

The weight variation values for all the formulated batch F1 to

F9 was found to be within the 5% acceptable limits.

In vitro dissolution studies

Table 9: Dissolution Data of Rabeprazole Core Tablet

Time F1 F2 F3 F4 F5 F6 F7 F8 F9

6.8pH phosphate buffer

15min 22.8 38.3 14.5 33.4 58.2 50.8 33.8 54.3 50.2

30min 45.3 52.8 38.9 52.1 75.6 76.1 68.2 92.4 80.1

45 min 62.1 72.6 59.2 66.8 90.9 92.4 91.6 95.6 99.9

60min 75.8 85.1 70.4 79.2 95.8 98.4 98.9 99.2 99.9

Fig 6: Percentage CDR of rabeprazole core tablet

In F9 formulation the concentration of Crospovidone was

optimized and found to have good flow property, and releases

99.9% of drug.

Evaluation parameters for enteric coated tablets

F9 formulation with highest drug release was selected for

coating. Four different coating polymers were used in four

different concentrations.

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Table 10: Post compression data of rabeprazole enteric coated tablet

Formulations Weight variation Hardness Thickness (mm) Friability (%) Acid resistance time Assay%(w/w)

EC 1 205 ± 0.05 3.5 ± 0.2 2.4 ± 0.05 0.44 ± 0.14 2hrs 95.3 ± 0.16

EC 2 205 ± 0.07 3.5 ± 0.1 2.4 ± 0.07 0.44 ± 0.12 2hrs 97.1 ± 0.17

EC 3 205 ± 0.04 3.5 ± 0.3 2.4 ± 0.1 0.44 ± 0.14 2hrs 99.9 ± 0.16

EC 4 205 ± 0.09 3.5 ± 0.1 2.4 ± 0.14 0.44 ± 0.16 2hrs 93.8 ± 0.19

EC 5 204 ± 0.1 3.5 ± 0.3 2.3 ± 0.03 0.55 ± 0.11 2hrs 99.9 ± 0.21

EC 6 204 ± 0.08 3.5 ± 0.05 2.3 ± 0.06 0.55 ± 0.15 2hrs 98.4 ± 0.20

EC 7 204 ± 0.05 3.5 ± 0.1 2.3 ± 0.08 0.55 ± 0.13 2hrs 95.6 ± 0.21

EC 8 204 ± 0.07 3.5 ± 0.07 2.3 ± 0.12 0.55 ± 0.16 2hrs 99.2 ± 0.19

EC 9 208 ± 0.09 3.5 ± 0.04 2.6 ± 0.01 0.48 ± 0.1 2hrs 95.3 ± 0.15

EC10 208 ± 0.11 3.5 ± 0.3 2.6 ± 0.05 0.48 ± 0.13 2hrs 96.6 ± 0.17

EC11 208 ± 0.15 3.5 ± 0.18 2.6 ± 0.09 0.48 ± 0.17 2hrs 97.2 ± 0.17

EC12 208 ± 0.13 3.5 ± 0.15 2.6 ± 0.18 0.48 ± 0.20 2hrs 97.9 ± 0.16

EC13 210 ± 0.18 3.5 ± 0.5 2.8 ± 0.03 0.45 ± 0.08 2hrs 93.2 ± 0.20

EC14 210 ± 0.06 3.5 ± 0.17 2.8 ± 0.08 0.45 ± 0.11 2hrs 94.8 ± 0.21

EC15 210 ± 0.05 3.5 ±0.06 2.8 ± 0.15 0.45 ± 0.15 2hrs 97.8 ± 0.16

EC16 210 ± 0.1 3.5 ±0.05 2.8 ± 0.2 0.45 ± 0.17 2hrs 99.2 ± 0.20

Dissolution study for enteric coated tablet

Table 11(a): Dissolution profile for rabeprazole enteric coated tablet

Time EC1 EC2 EC3 EC4 EC5 EC6 EC7 EC8

0.1 NHCL

5 min 0 0 0 0 0 0 0 0

15 min 0 0 0 0 0.002 0.001 0.0046 0.0028

30 min 0 0 0 0 0.009 0.007 0.009 0.008

45 min 0 0 0 0 0.012 0.013 0.017 0.019

60 min 0 0 0 0 1.07 1.02 1.089 1.02

75 min 0 0 0 0 1.35 1.56 1.67 1.42

90 min 0 0 0 0 1.92 1.96 1.93 1.87

120 min 0 0 0 0 2 2 2 1.94

5 min 10.02 23.45 35.10 21.69 31.26 35.02 25.26 10.97

15 min 21.11 35.47 50.28 30.93 53.89 47.04 31.30 13.43

30 min 41.95 48.89 85.56 48.24 70.01 70.47 72.41 36.02

45 min 57.50 67.23 97.5 61.86 84.17 85.56 84.82 54.82

60 min 70.19 78.80 98.3 73.34 92.41 92.69 91.58 65.19

75 min 78.20 80.21 99.1 77.16 95.03 94.22 93.5 80.14

90 min 83.19 92.28 99.9 88.24 96.22 96.95 94.1 91.4

120 min 95.3 97.1 99.9 93.8 97.2 98.4 95.6 92.7

Table 11(b): Dissolution profile for rabeprazole enteric coated tablet

Time EC9 EC10 EC11 EC12 EC13 EC14 EC15 EC16

0.1NHCL

5 min 0 0 0 0 0 0 0 0

15 min 0.001 0.003 0.001 0.0049 0.002 0.006 0.009 0.01

30 min 0.045 0.09 0.035 0.08 0.02 0.07 0.08 0.04

45 min 1.02 1.04 0.98 0.95 1.03 1.39 1.56 1.07

60 min 1.67 1.52 1.24 1.27 1.78 1.95 1.87 1.57

75 min 1.98 1.96 1.76 2.14 2.01 2.05 2.09 1.89

90 min 2.06 2.13 2.19 2.86 2.23 2.65 2.5 2.5

120 min 2.45 2.73 2.98 3 2.54 2.76 2.9 2.89

5 min 10.25 15.02 22.15 25.63 30.95 31.15 23.6 20.14

15min 13.49 25.47 29.43 37.93 53.89 47.04 31.30 45.06

30min 30.17 50.89 30.02 49.24 70.01 70.47 72.41 52.19

45 min 53.90 64.23 45.82 68.46 84.17 85.56 84.82 68.23

60min 73.25 82.80 69.19 73.34 92.41 92.69 91.58 87.63

75 min 80.4 83.10 87.3 79.15 92.56 92.9 92.8 90.9

90 min 89.7 85.35 90.7 83.05 93.0 93.25 96.73 95.34

120min 95.3 96.6 97.0 97.2 93.2 94.8 97.8 96.2

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Fig 7: Cumulative% drug release graph for formulation EC1-EC8

Fig 8: Cumulative% drug release graph for formulation EC9-EC16

Fig 9: Cumulative% drug release graph for formulation EC3 Vs

EC11 Vs EC15

Dissolution studies of all the formulations were carried

out using dissolution apparatus USP type

I. The dissolution studies were conducted by using dissolution

media, 0.1 N HCl for 2hrs and 6.8 pH phosphate buffer for

next two hours. The results of the in-vitro dissolution studies

of formulations EC1 – EC16, shown in table no.- The plots of

Cumulative percentage drug release Vs Time. Figure --

shows the comparison of% CDR for formulations EC1–

EC16.

The formulations EC3 showed a maximum release of 99.9

within 120 mins in 6.8pH Phosphate buffer after hours of acid

resistance.

Among all formulations EC 3 shows Maximum drug release

in 45 mins when compared with other formulations and the

natural polymers are also equally effective with a release of

97.2% for E12 and 97.8 for EC 15.

5. Conclusion

Rabeprazole enteric coated tablets were prepared by using

four different enteric coating polymers. The first two

polymers (synthetic) used for enteric coating are Eudragit

L100 and HPMC EC1 – EC8. These were used in the

concentration 2%, 4%, 6%, and 8%. The in-vitro dissolution

was carried out in 0.1 N HCL for 2 hours and in 6.8 PH

phosphate buffer for 2 hours. In 0.1 HCL the Eudragit L100

had zero drug release.

The natural polymers used for enteric coating were Sodium

Alginate and Shellac EC9 – EC16. The natural polymers were

coated in the concentration 2%, 4%, 6%, and 8%. The in-vitro

dissolution was carried out in 0.1 N HCL for 2 hours and in

6.8 PH phosphate buffer for 2 hours.

When comparing the natural and synthetic polymers, it can be

concluded that the in-vitro drug release showed Eudragit

L100 polymer with 6% concentration had 100% release in PH

6.8 Phosphate buffer, and sodium alginate with 8%

concentration and Shellac with 6% concentration exhibited

good release of 97.2% and 97.8% respectively.

The Eudragit L100 exhibited good performance but the

natural polymers are also equally effective. Instead of using

the synthetic polymers, natural polymers can be a good

alternative. Out of the two natural polymers that we used,

Shellac presented good performance when compared to

Sodium Alginate because Enteric coating of Sodium Alginate

is quite difficult and unreliable.

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ISSN (P): 2349-8242 Comparitive in-vitro drug release ... · Coating will protect the drug from the surroundings with a view to improve its stability. Coating can modify the drug