5481-5504, 1800, IJPT-14-0203, 30.05.13, FORMULATION …Email:[email protected] ... Low-substituted hydroxy propyl cellulose Vijilak Pharma Ltd Croscarmellose sodium Signet

Kotta Kranthi Kumar* et al. International Journal Of Pharmacy & Technology

IJPT | July-2013 | Vol. 5 | Issue No.2 | 5481-5504 Page 5481

ISSN: 0975-766X

CODEN: IJPTFI

Available Online through Research Article

www.ijptonline.com FORMULATION AND EVALUATION OF CLOPIDOGREL BISULFATE IMMEDIATE

RELEASE TABLETS USP 75MG

Kotta Kranthi Kumar*1, K.Sampath Kumar

2, G.Satheesh

3

Department of Pharmaceutics, S.K.U College of Pharmaceutical sciences S.K.University*1,

Anantapur,

Sri Lakshmivenkateseara Pharmacy College2 produttur, Krishnateja Pharmacy College Tirupathi

3.

Email:[email protected] Received on 02-06-2013 Accepted on 29-06-2013

Abstract

The present study relates to formulations comprising Clopidogrel, including pharmaceutically

acceptable salts thereof, which provide desired bioavailability. The aim of this study is to develop and evaluate

pharmaceutically equivalent, stable, cost effective and quality improved formulation of Clopidogrel bisulfate

immediate release tablets (at least 85% of the drug is dissolved in 30 min in each of three different aqueous media

(i.e., PH ranging from 1 to 6.8) using US pharmacopeia (USP) apparatus II at 100 rpm) and comparison of

dissolution rate of optimized formula with innovator’s product and estimation of similarity and difference

factors. In order to obtain acceptable product several trials w e r e c o n d u c t e d . Various pharmacopeia evaluations

of the formulations were conducted including weight variation, hardness, disintegration time, friability,

invitro dissolution. Final selection of formulation was done based on invitro drug release of development

formulation to that of marketed one. The optimized formulation was kept under stability conditions at 40oC ±

2oC / 75% RH conditions for 3 months as per ICH guidelines in HDPE containers and the product is to be stable

throughout the period.

Keywords: Clopidogrel bisulphate, immediate release, stability, ICH guidelines.

Introduction

Oral Drug Delivery1

Oral drug delivery is the most desirable and preferred method of administering therapeutic agents for systemic effects.

In addition oral medication is the first avenue investigated in the discovery and development of new drug entities and



pharmaceutical formulations mainly because of patient acceptance, convenience in administration and cost effective

manufacturing process. For many drug substances, conventional immediate release formulations provide clinically

effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with an

acceptable level of safety to the patient.

Based on desired therapeutic objectives, oral drug delivery systems may be assorted into three categories:

• Immediate- release preparations

• Controlled- release preparations

• Targeted- release preparations

Immediate Release Preparations

These preparations are primarily intended to achieve faster onset of action for drugs such as analgesics, antipyretics,

and coronary vasodilators. Other advantages include enhanced oral bioavailability through transmucosal drug delivery

and pregastric absorption, convenience in administration to dysphasic patients, especially the elderly and

bedridden and new business opportunities.

Conventional IR formulations include fast disintegrating tablets and granules that use effervescent mixtures, sodium

carbonate (sodium bicarbonate) and citric acid

(Tartaric acid) and super disintegrants such as sodium starch glycolate, Croscarmellose sodium and Crospovidone.

Current technologies in fast dispersing dosage forms include modified tableting systems, floss or shear form

technology, which employs application of centrifugal force, controlled temperature and freeze drying

Tablets: - 2-9

Tablet is solid dosage form each containing a unit dose of one or more medicaments. Tablets are solid, flat or biconvex

discs prepared by compressing a drug or mixture of drugs with or without suitable Pharmaceutical excipients tablets are

the dominant dosage forms for drug delivery, occupying two thirds of the global market. Generally, they are produced

by compressing dry powder blends consisting of a number of components with different functionalities in a die. With

advancement in technology and increase in awareness towards modification in standard tablet to achieve better

acceptability as well as bioavailability, newer and more efficient tablet dosage forms are being developed. The main

reasons behind formulation of different types of tablets are to create a delivery system that is relatively simple and in



expensive to manufacture, provide the dosage form that is convenient from patient’s perspective and utilize an

approach that is unlikely to add complexity during regulatory approval process.

Immediate Release Film Coating Systems for Tablets10-13s

The pigmented and non-pigmented film coatings are used for immediate release solid dosage forms. These film

coating formulas produce attractive, elegant coatings on even the most challenging tablet surfaces and can be used in

both aqueous and organic coating procedures. An extensive selection of polymer blend formulations provides the user

with the ability to impart many beneficial features to a solid oral dosage formulation.

These benefits include

• Reduced coating process time

• Superior adhesion on difficult to coat cores

• Less stressful processing conditions for heat sensitive, friable or high drug content cores

• Sharper logo definition, even at higher weight gains

• Better gloss and smoothness compared to conventional tablets

• Improved colour stability.

Aqueous film coating is the quickest and least expensive method for enhancing the tablet appearance and unlike other

methods, will not affect dissolution or disintegration profiles. The dry-blend systems consist of polymers, plasticizers

and pigments combined in one, easy-to-use and this dry powder system which is rehydrated quickly with water. Dry

coating technology provides benefits such as improved adhesion, reduced processing times and application of the

tablet coating at wider process parameters.

The aim of present work is to formulation of Clopidogrel Bi sulphate immediate release tablet and comparable to the

marketed product which could perform therapeutically, with improved efficacy.

MATERIALS14,15

All the materials and equipments are listed in Table No:-1, 2

Table No: 1: List of Materials

Material Source

Clopidogrel bisulphate Natco Pharma Ltd.



Microcrystalline Cellulose pH 102 Vijilak Pharma

Mannitol DC grade Signet Chemical Pvt Ltd

Low-substituted hydroxy propyl cellulose Vijilak Pharma Ltd

Croscarmellose sodium Signet Chemical Corporation Pvt Ltd

Lactose anhydrous Signet Chemical Corporation Pvt Ltd

Crospovidone / Polyplasdone XC Signet Chemical Corporation Pvt Ltd

Poly ethylene glycol 6000 Signet Chemical Corporation Pvt Ltd

L-HPC-LH-11 Signet Chemical Corporation Pvt Ltd

Hydrogenated castor oil Signet Chemical Corporation Pvt Ltd

Opadry pink32k84823 Signet Chemical Corporation Pvt Ltd

Croscarmellose sodium Signet Chemical Corporation Pvt Ltd

Table No.2: Equipment Used.

EQUIPMENT MODEL

UV-Visible Spectrophotometer Labindia UV 3000 Spectrophotometer

Digital Balance Essae model fb 3000 digital balance.

Sensitive Balance Keroy Km2 Sensitive Balance

PH

Meter Labindia Ph Analyzer

Tablet Punching Machine Cadmach single station tablet machine

Paddle Type Dissolution Apparatus Labindia Ds 800

FTIR Spectrophotometer Perkin Elmer, Japan

Hardness Tester Monsanto Ltd

Friability Apparatus Labindia Ft 1020 Tablet Friability Tester

Disintegration Apparatus Electro lab, mumbai.

Tray Dryer Sisco Tray Dryer

Hardness Tester Monsanto Hardness Tester

Experimental Session

Drug-excipient Compatibility Studies

A Compatibility study focuses on a binary mixture of drug substance and some selected excipients in a fixed ratio with

or without added moisture. The mixture stored at elevated temperatures as 40oc 75%RH, 55OC 60%RH in capped



vials. The result of the interaction between the active drug and excipients is determined by FTIR. The objective of this

study was to determine the interactions of Clopidogrel bisulfate with Excipients in the formulation.

Drug- Excipient compatibility studies are listed in Table no:-3

Table No-3: Procedure for drug- Excipient compatibility studies.

Ingredients Ratio Initial

Colour After one

week After two

weeks After

three

weeks

After four

weeks

40 0C

75%RH

40 0C

75%RH

40 0C

75%RH

40 0C

75%RH

Clopidogrel bisulfate 1:1 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+ MCC 1:5 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+Mannitol 1:5 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+ L-HPMC

(LH-21) 1:1 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder


(LH-21) 1:1 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+

Crospovidone 1:1 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder


polyethylene glycol 6000 1:0.5 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+ L-

Hydroxy propyl(LH-11)

1:1 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrelbisulfate+Hydrogenated

castor oil 1:0.5 White

granular

powder

White

granular

powder

White

granular

powder

White

granular

powder

White granular

powder

Clopidogrel bisulfate+Opadry II

pink 32K84823 1:0.5 Pink

granular

powder

Pink

granular

powder

Pink

granular

powder

Pink

granular

powder

Pink granular

powder

Manufacturing Methods 16, 17

Pharmaceutical products are processed all over the world using the direct compressing, wet granulation or dry

granulation methods. Method is chosen depend on the ingredients individual characteristics like flow property,



compressibility. Choosing a method requires thorough investigation of each ingredient in the formula, the combination

of ingredients, and how they work with each other. Then the proper granulation process cans be applied.

Formulation of different trial batches are listed in Table No:-4

Table no:-4: Formulation of Different Trials Batches.

S.No Composition* F1

Qty

F2

Qty

F3

Qty

F4

Qty

F5

Qty

F6

Qty

F7

Qty

F8

Qty

F9

Qty

F10

Qty

F11

Qty

F12

Qty

1. Clopidogrel bisulphate

(FORM II)

97.8 97.8 97.8 97.8 97.8 97.8 97.8 97.8 97.8 97.8 97.8 97.8

2. Microcrystalline cellulose

PH102

37.1 37.1 27.1 37.1 37.1 37.1 37.1 37.1 37.1 37 37.1 37.1

3. Mannitol DC grade 60 40 45 60 55 55 45 55 55 55 55 45

4. Low-substituted hydroxy

propyl cellulose(L-HPC) LH-21

10 3.0 15 10 15 15 15 15 15 10 10 15

5. Croscarmellose sodium 5 10 - 10 5 - 10 - 8 10 15 -

6. Lactose anhydrous - 10 15 - - 5 -

7. Crospovidone /

Polyplasdone XC

- - - 10 5 10 10 10 15 - 15 10

8. Poly ethylene glycol 6000 10 15 10 5 5 5 5 5 5 5 10 10

9. L-HPC-LH-11 10 10 5 10 10 10 10 10 13 10 10

10. Hydrogenated castor oil

(Cutina HRPH)

10 20 15 5 10 10 10 10 5 10 15

11. Opadry pink32k84823 - 7 6 - - - - 7 7 8 7

12. Purified water Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S

*The above all parameters are mentioned in mgs

Evaluation of Tablets18-37

Weight Variation Test:

This is an in process quality control test to be checked frequently (every half an hour). Corrections were made during

the compression of tablets. Any variation in the weight of tablets (for any reason) leads to either under medication or

overdose. So, every tablet in each batch should have a uniform weigh. The weight variation test was performed as per

USP. Twenty tablets were selected at random and their average weight was determined using an electronic balance.

The tablets were weighed individually and compared with average weight. The results were listed in Table no:-9



Hardness Test:

Hardness (diametric crushing strength) is a force required to break the tablet across the diameter. The hardness of a

tablet is an indication of its strength. The tablet should be stable to mechanical stress during handling and

transportation. The degree of hardness varies with the different manufacturers and with the different types of tablets.

The permissible limit for hardness is 4-12 kg/cm2. The hardness of the tablets was determined by digital hardness

tester. Ten individual tablets from each trial were taken and measured individually at frequent intervals. The results

were listed in table no:5-6.

Table No- 5: Standard specifications of weight variation test.

Average weight as per USP %Difference

130 mg or less 10

More than 130 mg

through 324mg

7.5

More than 324mg 5

Table No-6: Storage Conditions in Stability Studies.

Study Storage condition Minimum time

period covered

Long term 25ºC ± 2 ºC/ 60% RH ± 5% RH 12 months

Intermediate 30ºC ± 2 ºC/ 60% RH ± 5% RH 6 months

Accelerated 40ºC ± 2 ºC/ 75% RH ± 5% RH 6 months

Table No-7: Mechanism of drug release.

Diffusion exponent (n) Overall solute diffusion mechanism

0.45 Fickian diffusion

0.45 < n < 0.89 Anomalous (non-fickian) diffusion

0.89 Case-II transport

n > 0.89 Super case-II transport

Thickness

The thickness of the tablets was determined by digital micrometer. Ten individual tablets from each trial were taken

and measured individually at frequent intervals. The results were listed in table no: 9



Friability Test:

Friability of the tablets was determined by using Roche Friabilator (Electrolab, India). This device consists of a plastic

chamber that is set to revolve around 25 rpm for 4 minutes dropping the tablets at a distance of 6 inches with each

revolution. Friability was determined by taking 20 tablets. Tablets were weighed and placed in a Friabilator, after

specified time (4min at 25rpm) tablets were again weighed and the friability (F %) is given by the formula

F % = (1-W0 /W) ×100

Where, W0 is weight of the tablets before the test and W is the weight of the tablets after test. The results were listed

in table no:-9

Disintegration Test:

Disintegration time was measured using USP disintegration test apparatus (ED2L, Electrolab, India by using 900ml

distilled water at room temperature (37±20oC) The results were listed in table no:-9

Dissolution Test parameters

Medium: pH 2.0 HCl, pH 4.5 sodium acetate buffer, Ph 6.8 phosphate buffer

Apparatus: paddle type Speed: 50 rpm Temperature: 37±0.5°C Run time: 30 min

Dissolution Test Procedure:

6 tablets were placed in each of 6 dissolution flasks containing 900 m l of pH 2.0 HCl maintained at 37±0.5°C.

The apparatus was run for 30 minutes. A suitable volume of sample was withdrawn at regular intervals of time and

filtered through 0.45 µm membrane filter. The absorbance of the sample preparations were measured at 249 nm, using

pH 2.0 HCl as blank The results were listed in table no:-10

Similarity and Difference Factors

For each dissolution run, a mean of six determinations was recorded for marketed product. Thein vitro dissolution of

clopidogrel bisulfate immediate release tablets were prepared and matched with innovator product by calculating the

similarity and difference factors. A model independent approach was used to estimate the dissimilarity the dissolution

profile of optimized formulation (F8) with innovator’s preparation. The following equations were used for calculating f1

and f2.



The fallowing equation given

Where

n = no of time points,

Rt = dissolution value of the reference batch at time t,

Tt=dissolution value of the test batch at same time point.

The results were listed in table no:13

Stability Studies

The design of the formal stability studies for the drug product was based on the knowledge of the behavior and

properties of the drug substance and formal stability studies on the drug substance. Specification which is list of tests,

reference to the analytical procedures and proposed acceptance criteria, including the concept of different acceptable

criteria for release and shelf life specifications, is addressed in ICH (Temperature: 40±2oC Relative humidity:

75±5% for 3 months).T he results were listed in table no:-14

When significant change occurs at any time during 6 months testing at the accelerated storage condition, additional

testing at the intermediate storage condition should be conducted and evaluated against significant change criteria.

Release Kinetics: The mathematical models are used to evaluate the kinetics and mechanism of drug release from the

tablets. The model that best fits the release data is selected based on the correlation coefficient (r) value in various

models. The model that gives high ‘r’ value is considered as the best fit of the release data.

Mathematical models are

1) Zero order release model

2) First order release model

3) Hixson-crowell release model

4) Higuchi release model

5) Korsmeyer – peppas release model



Zero order release rate kinetics:-

To study the Zero order release kinetics the release rate data were fitted to the following equation.

F = K t

Zero order release rate kinetics:-

To study the Zero order release kinetics the release rate data were fitted to the following equation.

F = K t

Where,’F’ is the fraction of drug release,

‘K’ is the release rate constant, and‘t’ is the release time.

When the data is plotted as Cumulative percent drug released versus time, if the plot is linear then the data obeys Zero

order release kinetics, with slope equal to K.

The results are given in table.

First order kinetics:-

A First order release would be predicated by the following equation.

K t

Log C = Log Co - ----------

2.30 3

Where = Amount of drug remained at time‘t’

Co = initial amount of drug

K = First order rate constant (hr-1)

When the data is plotted as Cumulative percent drug remaining versus time yields a straight line, Indicating that the

release follows First order kinetics .The constant ‘K’ can be obtained by multiplying 2.303 with slope value.

Higuchi release model: -

To study the Higuchi release kinetics, the release rate data were fitted to the following equation.

F = K. t1/2

Where,’F’ is the amount of drug release

‘K’ is the release rate constant, and



‘t’ is the release time.

When the data is plotted as Cumulative drug released Versus Square root of time, yields a straight line, indicating that

the drug was released by diffusion mechanism .The slope is equal to ‘K’.

Korsmeyer and peppas release model: - The release rate data were fitted to the following equation.

Mt / M∞ = K. t n

Where, Mt / M∞ is the fraction of the drug release,

‘K’ is the release rate constant,

‘t’ is the release time, and

‘n’ is the diffusional exponent for the drug release that is dependent on the shape of the matrix dosage form. When the

data is plotted as Log of drug released Versus log time, yields a straight line with a slope equal to ‘n’ and the, ‘K’ can

be obtained from Y-intercept.

All the results are reported in the table no: 16

Results

All the results are listed in Table No:-8-16

Summary and Conclusion

The present study was undertaken to develop Clopidogrel bisulfate immediate tablets of 75mg, comparable to the

innovators product (Plavix-sanfoi aventis). Based on the results, suitable excipients were selected for formulation

development. Various formulas of Clopidogrel bisulfate were prepared by using direct compression method. The

powder blend were subject to various physical characteristics tests such as bulk density, tapped density,

Hausner’s ratio, compressibility index and core tablets were evaluated for weight variation, hardness, thickness,

disintegration time and the results were within specification. Compatibility studies were performed and it was observed

that all the ingredients used were compatible with the drug. As Clopidogrel possess stability problem core

tablets were coated with coating suspension and were evaluated for disintegration time, assay and In-vitro release

studies. In-vitro dissolution profile of developed formula was compared with innovator’s product (Plavix) and drug

release from developed formula was found to be similar to innovator product and compared with the reference product



of Plavix. The optimized batch tablets were packed in HDPE containers and performed stability studies at

40°C/75%RH. Stability samples were evaluated initially and after two months.

Table No-8: Drug Excipient compatibility studies.

Ingredients Ratio Initial

Colour After

one

Week

After two

weeks After

three

weeks

After

four

weeks

40 0C

75%RH 40

0C

75%RH 40

0C

75%RH 40

0C

75%RH

Clopidogrel bisulfate 1:1 White

granular

powder

NCC NCC NCC NCC

Clopidogrel bisulfate+ MCC 1:5 White

granular

powder

NCC NCC NCC NCC

Clopidogrel bisulfate+Mannitol 1:5 White

granular

powder

NCC NCC NCC NCC


(LH-21) 1:1 White

granular

powder

NCC NCC NCC NCC


Crospovidone 1:1 White

granular

powder

NCC NCC NCC NCC


polyethylene glycol 6000 1:0.5 White

granular

powder

NCC NCC NCC NCC

Clopidogrel bisulfate+ L-

Hydroxy propyl(LH-11)

1:1 White

granular

powder

NCC NCC NCC NCC

Clopidogrelbisulfate+Hydrogenated

castor oil 1:0.5 White

granular

powder

NCC NCC NCC NCC

Clopidogrel bisulfate+Opadry II

pink 32K84823 1:0.5 Pink

granular

powder

NCC NCC NCC NCC

NCC-No colour change

Table No-9: Post Compression Parameters.

S.no Formulation Average

weight(mg)

Thickness Disintegration

min

Friability Assay Hardness

1 F-1 246.8 3.63±0.099 40.16 0.153±0.56 96.4±0.79 4.2±0.31

2 F-2 246.90 3.62±0.016 3.02 0.106±0.76 97.3±0.76 5.3±0.42

3 F-3 247.50 3.43±0.035 8.5 0.377±0.65 94.1±0.56 10.44±0.49

4 F-4 247.80 3.46±0.024 14.55 0.24±0.54 98.5±0.76 2.75±0.51



5 F-5 246.70 3.48±0.029 11.5 0.17±0.86 97.4±0.87 6.09±0.24

6 F-6 246.8.55 3.47±0.053 11.2 0.28±0.76 90.3±0.79 5.46±0.32

7 F-7 246.90 3.53±0.022 12 0.23±0.45 92.4±0.67 9.45±0.59

8 F-8 247.12 3.5±0.022 10 0.5±0.56 99.8±0.56 2.9±0.47

9 F-9 245.80 3.55±0.019 5.5 0.06±0.59 98.5±0.98 9.6±0.35

10 F-10 245.32 3.54±0.016 12 0.16±0.57 98.2±0.76 7.1±0.27

11 F-11 246.9 3.53±0.02 13.02 0.4±0.45 98.3±0.45 3.5±0.13

12 F-12 247.8 3.55±0.016 13.53 0.5±0.79 97.4±0.76 4.0±0.56

All the values are expressed as mean ± S.D; No. of trails (n) =6

INFERENCE: All the formulation trials were within the specifications and F8 formulation showed appreciable results of

physical properties.

Table No:-10: Dissolution Results of Trial Batches.

S .NO TIME

(min)

F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12

1. 0 0 0 0 0 0 0 0 0 0 0 0 0

2. 10 60.6 61.1 63.7 54.5 59.3 61.3 62.4 62.7 54.1 54.5 48.3 53.1

3. 15 80.2 74.3 74.1 72.3 74.3 74.5 73.6 78.8 77.8 81.2 75.7 74.3

4. 20 82.9 82.9 86.4 88.7 88.7 92.1 86.7 90.4 85.3 88.3 88.3 88.6

5. 30 95.6 96.6 94.5 91.5 91.5 96.6 91.8 99.3 90.3 90.4 90.8 98.3

Table No-11: Invitro Drug Release of Optimized Batch.

TIME

(min)

% of drug release F8

0 0

10 62.7

15 78.8

20 90.4

30 99.3



Table No: 12: Comparative Dissolution Profile of F8 Formulation and Innovator.

TIME F8 INNOVATOR

0 0 0

10 62.7 54

15 78.8 74

20 90.4 88

30 99.3 98.3

INFERENCE: The drug content of optimized formulation was equivalent to the innovator’s product

Table No-13: Similarity and Difference Factors.

N INNOVATOR

(Rt)

F-8

(Tt)

D=(Rt-Tt) (Rt-Tt)2 f 1 f 2

0 0 0 0 0

5.15

64.29

10 54 62.7 -8.7 75.69

15 74 78.8 -4.8 23.04

20 88 90 -2 4

30 98.3 99 -0.7 0.49

Table No-14: Stability Studies of Optimized Formulation.

CONDITIONS

Sl. no Assay(%w/w) Initial 40c & 75% RH

0 Day 1 month 2month 3month

1 Optimised

formulation (F8)

100.3

99.8

99.5

99.6

2. Innovator 100 99.8 99.6 99.6

INFERENCE: The assay values are within the specifications



Table No-15: Dissolution of Optimized Formulation and Innovator.

Time

(min)

Initial 1

st month 2

nd month 3

rd month

0 0 0 0 0

10 62.7 62.7 62.7 62.7

15 78.8 78.8 78.8 78.8

20 90.4 90.4 90.4 90.4

30 99.3 99.3 99.3 99.3

Table No-16: First Order Kinetics.

Time

(min)

% drug

release

% drug

remained

Cumulative %

drug remained

Log cumulative %drug

Remained

0 0 100 62.7

1.797267541

10 62.7 37.3 15.6

1.193124598

15 78.8 21.7 11.7

1.068185862

20 90 10 9

0.954242509

30 99 1 0 0

Drug- Excipient studies by FTIR

Fig no-1: FTIR spectra of Clopidogrel bisulfate



Fig No-2: FTIR spectra of Clopidogrel bisulfate + Crospovidone.

Fig No-3: FTIR spectra of Clopidogrel bisulfate+ hydrogenated castor oil.

Fig No-4: FTIR spectra of Clopidogrel bisulfate + Mannitol.



Fig No-5: FTIR spectra of Clopidogrel bisulfate + PEG 6000.

Fig No-6: FTIR spectra of Clopidogrel bisulfate +LH- 11.

Fig No-7: FTIR spectra of Clopidogrel bisulfate +LH 21.



Fig No-8: FTIR spectra of Clopidogrel bisulfate + Opadry pink.

Fig No:-9: FTIR spectra of placebo

INFERENCE: Drug Excipient stability studies showed no conformational changes in formulations and

found to stable at environmental condition as defined by ICH guidelines and there was no interaction or

physical change between the drug and Excipients. So the selected Excipients were found to be compatible with

the drug.

Fig No:-10



Fig No-11: Invitro % drug release of optimized formulation in pH2.0 HCL buffer

Fig No-12: Comparison of F8 formulation with the innovator.

Fig No-13: Chromatogram of optimized formulation.



Fig No-14: Chromatogram of Innovator’s product.

INFERENCE: The drug content of optimized formulation was equivalent to the innovator’s product

Fig No-15: Dissolution profile of optimized batch for stability studies.

Fig No-16: First order kinetics.

INFERENCE: The optimized formulation has followed first order kinetics due to its invitro drug release was 90% in

20 min.



Conclusion

From the results obtained, the In-vitro dissolution profile of formula 8 was somewhat better to that of reference

product. All the stability results were found to be satisfactory. Hence the designed and developed formula of

Clopidogrel was stable. Clopidogrel bisulfate immediate release tablets developed in the present work was found to be

pharmaceutically better than the innovators product.

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Corresponding Author:

Kotta Kranthi Kumar*,

Email:[email protected]

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