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Rumaisa DM et al., 2013 13

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Int. Res J Pharm. App Sci., 2013; 3(3):13-17

THE ACUTE TOXICITY OF METHANOLIC EXTRACT OF EURYCOMA LONGIFOLIA JACK

ROOTS AND HISTOPATHOLOGIC CHANGES OF RAT VITAL ORGANS 1Rumaisa Dhifa Mawaddah,

2Firdalena Meutia,

3Sofia,

4Hanifah Yusuf

1Faculty of Medicine University of Syiah Kuala Darussalam Banda Aceh 23111 2,4Departement of Pharmacology Faculty of Medicine University of Syiah Kuala Banda Aceh 23111

3Departement of Biochemistry Faculty of Medicine University of Syiah Kuala Banda Aceh 23111

. (Received: 20 May 2013; Accepted: 23 June, 2013; Published: 30 June, 2013) Corresponding Author’s email: hans_yusuf1104@yahoo.com

Abstract: The acute toxicity of methanolic extract of Eurycoma longifolia Jack roots have been studied on rats. The study was based on increasing used of E. longifolia Jack roots for maintaining health and treatment by the people. This experimental study

used “completely randomized design” and 30 rats were divided in 5 groups (n = 6 each group) for treated and control group. The

rats were given tested extract with a single dose 0; 25; 75; 225; 625 mg/kg BW/day orally. The observed parameters were the fifty

percent of lethal dose, its influences on toxicological profile, the development of body weight and mortality. The microscopic

observation of vital organ (kidney, stomach, and liver) have been done on fifteenth day. The results of acute toxicity test after

giving the single dose extract to males and females rats showed that the fifty percent of lethal dose (LD50) is 7498.94 mg/kg BW,

orally. The increasing of body weight was shown on dose 75 mg/ml and 225 mg/kg BW. Hematoxylin-eosin stain was used to

evaluate the histopathologic changes of rat vital organs (kidney, liver , heart, stomatch) and showed the apparent change on dose

675 mg//kg BW like necrosis. The symptom of toxicity were shown on dose 225 and 675 mg//kg BW such as depression,

shallow breath, convulsion, coma and then died.

Keywords: Acute toxicity, LD50, Eurycoma longifolia Jack..

INTRODUCTION

The increasing of drug prices and the limited purchasing power of people, making traditional medicine as

an alternative for the purpose of maintaining their own

health and treatment1. Although the use of traditional

medicine is widespread and entrenched, but its use has not

been supported by scientific study as well as modern drugs.

The truth efficacy and safety of a drug, including traditional

medicines have been proven through a scientific study and

the test is performed to prove the safety of a drug, known as

toxicity tests. Toxicity test not only for modern drugs but

also important for traditional medicine, especially for

traditional medicine most commonly consumed by the

people.

One of the most popular traditional medicine is

Eurycoma longifolia Jack, known as “tongkat ali“ or

“pasak bumi” plant in Indonesia. Eurycoma longifolia

Jack is the most widely used traditionally to treat a variety

of diseases such as malaria, inflammation, aphrodisiac,

cancer and as a tonic drug2. In Malaysia, the roots of this

plant is best known as an aphrodisiac to address male sexual

dysfunction3,4.

The roots of this plant contain compounds such as quassinoids, xanthinon alkaloids, β carboline alkaloids,

triterpene trycullane, squalene and biphenolneolignane

derivatives5. The main compounds are a class of quasinoid

with skleton structure composed of C18, C19, and C20.

Extraction is performed on the root of E.longifolia Jack

standardized contains quassinoid with three main types

namely, eurycomanone, 13 β, 21 α-dihydroeurycomanone and 13 21-epoxyeurycomanone6 have reported that

quassinoid include eurycomanone as antimalarial,

euryomanol and 13 - (β -epoxy) eurycomanone efficacious

as antiulcer.

The scientific studies of the roots, contain

quassinoid derivatives that active against Plasmodium

falciparum in vitro6. The other studies have suggested that

the roots of E. longifolia Jack which grown in Thailand

contain quasinoid that have antimalarial activity and

cytotoxic effects7. Its antiplasmodial activity was tested in

vitro and eurycomanone is the most potent active compound and have cytotoxic effects against nasopharyngeal epidermal

cells carcinoma8.

Beside that, the extract can raise blood levels of

testosterone9. Based on pharmacological studies obtained

information that compounds in this plants can inhibit cancer

cell growth, whereas quasinoid compound also serves as a

potential anti-leukemia and anti-HIV10.

The chemical compounds contained within the

E. longifolia, Jack has attracted the attention of many researchers due to a fairly broad biological activity9.

Traditional medicinal products containing the roots of

this plant attracted many people in the world, not only

because it can cure malaria, cancer, aphrodisiac, but

this natural ingredient is also the most widely used as

Research Article

Int. Res J Pharm. App Sci., 2013; 3(3):13-17 ISSN: 2277-4149

Rumaisa DM et al., 2013 14

an ingredient in the drug-tonic10. Its use as a tonic is

very popular not only consumed by men but also used

by women11.

In addition to in vivo studies in mice infected

Plasmodium berghei, were obtained ED50 values between

11.2 mg / kgBW12. But in the study of acute toxicity tests

of ethanolic extract orally in mice, LD50 values has

obtained 2.6 g / kg BW, and the symptoms of toxicity

were found such as depression, shallow breathing and

convulsions, in that study 95% of mice died at a dose of 0.43 g / kg13.

Acute toxicity test of methanolic extract of E.

longifolia Jack roots through oral administration in rats

has not been done. The widespread use of traditional

medicines containing E.longifolia Jack roots in the

community, it is felt necessary by the researchers to

assess the acute toxicity on rats that can be known the

safety limits. It is hoped that the results of this study

can be useful as an initial information to the public to

prevent side effects or toxic effects resulting from the

use of traditional medicines containing the roots of E. longifolia uncontrolled14.

Based on the things mentioned above, this study

was conducted to determine the median lethal dose (LD50)

of methanolic extract of E. longifolia Jack roots on rats, the

symptoms of toxicity, the profile change of vital organs

microscopically after oral administration15.

MATERIALS AND METHODS

Materials:

The roots of E. longofolia Jack were collected from 4 years old plants that grown in Study Forest Park, Faculty

of Forestry University of Lambung Mangkurat, Banjar Baru,

South Kalimantan. The root have been deposited and

identified by a specialist (Prof Dr.Wahyono,SU) from

Departement of Biology Pharmacy, Faculty of Pharmacy

University of Gadjah Mada. A voucher speciment No

BF/123/Ident/Det/III/2010. In this study the methanolic

extract of E. longifolia Jack roots is used as test drug that

made by standard method.

Preparation of White Rats (Rattus norvegicus)

Experimental animals (rats) were acclimatized for 1 week before the study is done in a way kept in cages

measuring 50 x 30 x 50 cm with each cage containing 6

individuals (male and female, five groups, n=6). Cages

placed in a room kept clean, with a 12-hour cycle of light

and 12 hours of dark light. Prior to testing, animal were

weighed and then fasted for 12 hours but the water is still

given, then taken to a laboratory for adaptation to the

environment. Food animal given back 6 hours after

administration of the test drug16. The study protocol was

appoved by Animal Ethics Comittee, Faculty of Medicine

University of Syiah Kuala

Acute Toxicity Test Procedure and Parameters

The serial test dose given only once, on day 1 after

acclimatization. Serial test dose of the extract administered

orally (25 mg/ml, 75 mg/ml, 225 mg/ml, 675 mg/ml) using a

metal sonde to experimental animals (1 ml/200g BW). As a

negative control is used distilled water.

The observation of toxicity symptoms in the form

of behavioral changes conducted 0.5 - 1, 1.5 – 2, 3-6 hours

after administration of the test dose. Development of the

body weight of rats was measured three (3) times during 1

week, that is on day 1; 3; 5 and day 7 after administration of

the test drug and the number of deaths was calculated for 24

hours on day 1.

Subsequently the animals were still alive and observations continued 2 times a day for 14 days. On day 15

the autopsy was performed by microscopic examination of

the kidney, liver, heart and stomach. The development of

body weight and the profile changes of vital organ were

measured and compared with the control group.

Furthermore the number of the rats death in the treatment

group used to calculate lethal dose 50 (LD50) by the method

of Weil CS (1952).

Histological Assessment

Rats were sacrificed by cervical dislocation and subsequently kidney, liver, heart and stomach collected from

each rat and fixed with 10 % buffered formalin. Paraffin

blocks were prepared and sections of 5μm were cut on a

microtome and stained with hematoxylin and eosin. The

tissue sections were examined and compared with negative

controls.

Data analysis

All data were collected and processed statistically,

the lethal dose 50 (LD50) was calculated by the method Weil

CS (1952). The body weight development between

treatment groups were examined using Analysis of Variance (ANOVA) at the level of significance 0.05 and the results

were expressed as mean ± SD. The symptoms of toxicity or

changes in animal behavior qualitatively assessed by

Ngatidjan guide (2006).

RESULT AND DISCUSSION

The result of maceration process of E. longifolia

Jack powdered roots yielded 50 gram of dark brown extract.

The number of animals death were 3 of tested group with dose 225 mg/kg BW and 6 with dose 675 mg/kg BW and

the observation performed for 24 hours after oral

administration of the extract. Animal mortality data were

used to calculate lethal 50 dose (LD50) using the method of

Weil CS manually and obtained LD50 value 7498.94 mg/kg

BW.

The LD50 is defined as "a single dose of a

compound that is statistically expected to kill 50% of test animals". Other researchers obtained LD50 value of the

methanolic extract in mice of 6.180 mg / kg13, whereas the

LD50 value of the ethanolic extract in mice at 2600 mg / kg

orally.

Int. Res J Pharm. App Sci., 2013; 3(3):13-17 ISSN: 2277-4149

Rumaisa DM et al., 2013 15

The difference in the LD50 value of the extract can

be affected by various factors, such as the concentrations of

compounds present in the extract, species, age, weight, sex

of animal used, nutritional, environmental temperature,

humidity, and air circulation. Besides that the LD50 value is

also influenced by health factors, animal stomach contents,

route of administration and dosage form drug testing and

how the implementation of the acute toxicity test.

The observations on the development of animal

body weight (rats) were performed for 7 days after administration of a single dose of the extract. Weighing

were performed before treatment on day 1; 3; 5 and 7 after

oral administration of the extract shown in Table 1. The

result showed that on day 1 there was no significant

difference between all treatment groups. The same analysis

conducted on the development of body weight on day 3, the

results showed that there was no significant difference

between the control groups vs. group 25 mg /kg BW, as well

as between group 75 mg / kg BW vs group 225 mg /kg BW.

However, a significant difference (*) was seen between the

control groups vs 75 and 225 mg/kg BW. On day 5 there is a

significant difference (*) between all treatment groups, except between group 75 and 225 mg/kg BW. Whereas on

day 7 there are significant differences (*) between all dose

groups, except group 75 and 225 mg/kg BW.

The weight development in 675 mg/kg BW group

can be observed only on day 1, because all experimental

animals in this group died within 24 hours after being

treated with the extract. The decrease or increase in body

weight in animals due to treatment is also influenced by

various factors such as: nutrition, environmental

temperature, the potential toxicity of the compound

contained in the extract.

Symptoms of toxicity animals were observed

before and after administration of single dose and the

behavioral observation covers locomotoric activity, central

nervous and autonomic nervous system, defication and

urination (Thompson, 1985). Oral single dose administration

of the extract didn’t affect the behavior of male and female rats compared to controls group during the intensive

observation in 0,5 -1 hour. However, after 1.5 - 2 hour

administering a single dose of the extract showed an

increase in locomotor activity behavior and aggressiveness.

Sensitivity to pain slightly increased in group dose 225 and

675 when compared with the control group. Reflexes and

awareness increased with increase in dose while the

respiratory rate showed more increased in those groups.

On behavioral observations after 3-6 hours of the

extract in group 225 to group 675 showed significant

differences in behavior compared to the control group. The acute toxicity test results after administration of the extract

with single dose 675 mg /kg BW orally seen a decrease in

locomotor activity, aggressiveness, reflexes, awareness and

tremor when compared to the control group. While

symptoms of toxicity begin to occur in toxic doses 225 - 675

mg / kg BW in the form of depression, shallow breathing,

convulsions, coma and death.

Table 1. The Development of Rats Body Weight on Acute Toxicity of The Extract Eurycoma longifolia Jack Roots

Level doses (mg/kg

BW)

Rats Body Weight

Day 1* Day 3** Day 5** Day 7**

0 158,95 ± 5,21 134,52 ± 5,49 169,38 ± 7,75 155,47 ± 6,03

25 159,28 ± 7,16 133,15 ± 8,03 151,33 ± 9,88 162,50 ± 9,84

75 177,78 ± 12,49 153,73 ± 11,01 191,32 ± 14,07 191,23 ± 14,68

225 181,22 ± 7,18 152,40 ± 2,16 187,20 ± 9,01 199,20 ± 14,50

675 185,87 ± 10,30 - - -

* before given the extract of E.longifolia Jack roots ** after given the extract of E.longifolia Jack roots

Int. Res J Pharm. App Sci., 2013; 3(3):13-17 ISSN: 2277-4149

Rumaisa DM et al., 2013 16

A B C D

E F G H

Histologic specimens of rats tissues were collected

after 16 days of treatment. Tissue samples were stained with

hematoxylin and eosin. The histological pictures were taken

at following magnifications at 400x (A: Kidney; C: Liver; E:

Heart; G: Stomatch of control grroup) and (B: Kidney; D:

Liver; F: Heart; H: Stomatch of treated grroup in dose 675

mg/kg BW).

Conclusions

The lethal 50 dose (LD50) of methanolic extract of Eurycoma longifolia Jack roots using the method of Weil

CS manually were obtained LD50 value 7498.94 mg/kg BW,

orally. The administration of a single dose of the extract

with doses up to 225 mg / kg BW affect on the development

of animal body weight (rats) during the 7 days of

observation. The extract in oral administration on rats affect

behavior primarily locomotor activity, aggressiveness,

reflexes, awareness, sensitivity to pain and respiratory

system. While symptoms of toxicity begin to occur in toxic

doses 225 - 675 mg / kg BW in the form of depression,

shallow breathing, convulsions, coma and died.

Acknowlegment

The authors are grateful to Prof. Dr. Mustofa, M.Kes

from Departement of Pharmacology and Toxicology for his

assistance. Authors would like to thank Ria from

Departement of Biology Faculty of Mathematic and Natural

Science University of Syiah Kuala Banda Aceh Indonesia

for her assistance.

REFERENCES

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L.A., Sindelar, R.D. Biologically Active Quassinoid and Their Chemistry: Potensial Leads for Drug

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Indonesia, 2000.

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Ohighasi H. Quassinoids from Eurycoma longifolia

as Plant Growth Inhibitors. J Phytochemistry, 2001;

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Antiparasitic Activities of The Quassinoid from

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Eurycoma longifolia, J. Bioorg Med Chem, 2004; 12:

537 -544.

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GMS Publishing Corp. Manila. 1978, p37-55.

14. Morita H, Kishi E, Takeya K, Itokawa H, Tanaka O.

New Quassinoid from the Roots of Eurycoma

longifolia. J Chemistery Letters, 1990; 749-752.

15. Mustofa dan Solikhah EN. In Vivo and In Vitro

Antimalarial Activity of Extract of Eurycoma

longifolia Jack Roots, Swietenia mahogony L.

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Please read the following instructions carefully or any query, contact us at:managingeditors@irjpas.com or irjpas@gmail.com Preparation of ManuscriptAll type of Manuscripts should be prepared as Microsoft­word documents in Times New Roman (font size should be 12)on A4 size with a margin of 1 inch of all four sides. The manuscript should be typed double­spaced including references and tables also.All figures and tables should be at appropriate place in the text. Research Article:The manuscript should be in the following order: Title page: It should have Title, Name(s) of author(s) and their affiliations i.e. postal address, phone no., correspondingauthor’s email address. Abstract: It should have a brief idea of the manuscript and not exceed 250 words. Keywords: It should contain up to 5 key terms related to the research work. Introduction: It should represent the scope, objective and novelty of the research work. Experimental Section: It should contain information about the materials and the methods adopted to carry out theresearch works. Results and Discussion: It should contain summary of the research work performed, result interpretations and finallytheir Conclusion: It should contain about the out come and your view on the work. Acknowledgements: It should contain the information regarding any research grant support or the assistance ofcolleagues. (If any) Review Articles:It is expected that these articles would be written by individuals who have done substantial work on the subject or areconsidered experts in the field. A short summary of the work done by the contributor(s) in the field of review shouldaccompany the manuscript. The manuscript should have an Abstract (250 words) representing an accurate summary of the article. The section titleswould depend upon the topic reviewed. Short communications/Case reports:Articles which are not in length as full article can be submitted as short communications. New and interesting facts canbe reported. These communications could be of up to 1000 words (excluding Abstract and references). Letter to the Editor:These should be short and decisive observations. They should preferably be related to articles previously published inthe Journal or views expressed in the journal. They should not be preliminary observations that need a later paper forvalidation. The letter could have up to 500 words and 5 references. It could be generally authored by not more than fourauthors. Other:Editorial, Guest Editorial, and Commentary are solicited by the editorial board. References: The references should be represented as superscript e.g .1 in the text.The references pattern should be in the following manner: For a journalAuthors Surname Initial. Title, Journal, Year; Volume (Issue): Page No.Habibur Rahman, Muralidharan P. Comparative study of antidepressant activity of methanolic extract of NardostachysJatamansi DC Rhizome on normal and sleep deprived mice, Der Pharmacia Lettre, 2010; 2(5): 441­449 A book and other MonographAuthors Surname Initial. Title, Edition, Publisher, Place of publication, Year of publication; Page NoTripathi KD. Essentials of Medical Pharmacology, sixth Edition, Jaypee Brothers Medical Publication (P) Ltd, NewDelhi, 2008; 89­90 ThesisAuthors Surname Initial. Title, University, Place, Year; Page NoMohan K, Experimental evaluation of an antibiotic by nasal delivery system, M.S University, Chennai, 2010; 56­78 Electronic Sources as referenceAmerican Medical Association [homepage on the Internet]. Chicago: The Association; c1995­2002 [updated 2001 Aug 23;cited 2002 Aug 12]. AMA Office of Group Practice Liaison; [about 2 screens]. Available from: http://www.ama­assn.org/ama/pub/category/1736.html

International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. AppSci. www.irjpas.com

Chief EditorDr. M. Chinna Eswaraiah

Managing Editors

Mr. Md. Habibur RahmanMr. A. Elumalai

12/31/2014 IRJPAS

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Submission of Manuscript: Manuscript should submit along with a cover letter electronically to the email IDs irjpas@gmail.com and orsubmit@irjpas.com Publication feesThere is no publication fees/ per author fee. But for maintain article in data bases, website authors have to pay Articleprocessing fees on each article. A maximum of five authors can be in one article. The article processing fees on eacharticle is as follows­ Article Type Article Processing FeesResearch Article Rs. 1050 (In India), USD $ 25 (Foreign)Review Article Rs. 750 (In India), USD$ 20 (Foreign)Short communications/ Case Reports Rs 500 (In India), USD $15(Foreign)

N.B: Review articles, Short communications, Letters to the editors or case reports can be arranged asrequirements of the article.

Instruction to Author Copy Right Form Model Cover Letter

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Pharmaceutics

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Manuscript Submission Authors are strongly recommended to prepare the manuscript as IRJPAS authors guidelines and submit theirmanuscript along with cover letter preferably by the corresponding author electronically through an E­mail address to ­

submit@irjpas.com and/or irjpas@gmail.com Each manuscript status will be provided with a manuscript ID Number by IRJPAS editorial team within 1­2 days by E­mail after submission.

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International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. AppSci. www.irjpas.com

Chief EditorDr. M. Chinna Eswaraiah

Managing Editors

Mr. Md. Habibur RahmanMr. A. Elumalai

12/31/2014 IRJPAS

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Content

International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. App Sci. www.irjpas.com

Volume­4:Issue­5 (Sep­Oct, 2014)Volume 4 Issue5Volume­4:Issue­4 (Jul­Aug, 2014)Volume 4 Issue4Volume­4:Issue­3 (May­Jun, 2014)Volume 4 Issue3Volume­4:Issue­2 (Mar­Apr, 2014)Volume 4 Issue2Volume­4:Issue­1 (Jan­Feb, 2014)Volume 4 Issue1Volume­3:Issue­6 (Nov­Dec, 2013)Volume 3 Issue6Volume­3:Issue­5 (Sep­Oct, 2013)Volume 3 Issue5Volume­3:Issue­4 (Jul­Aug, 2013)Volume 3 Issue4Volume­3:Issue­3 (Jun­2013)Volume 3 Issue3Volume­3:Issue­2 (Apr­2013)Volume 3 Issue2Volume­3:Issue­1 (Feb­2013)Volume 3 Issue129­12­2012(2012)Volume 2 Issue629­10­2012(2012)Volume 2 Issue529­08­2012(2012)Volume 2 Issue429­06­2012(2012)Volume 2 Issue329­04­2012 (2012)Volume 2 Issue229­02­2012(2012)Volume 2 Issue120­12­2011(2011)Volume 1 Issue101­05­2012 (Suppl.2012)Volume 2 Issue2

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Home Editorial Board Instruction to Authors Manuscript Submission Archives Subcription Contact Us

Pharmaceutics

Pharmacology

Medicinal Chemistry

Pharmacognosy

Natural Chemistry

Pharmaceutical Analysis

Nanotechnology

Industrial Pharmacy

Pharmacy Practice

Novel Drug Delivery

Biopharmaceutics

Pharmacokinetics

Computational Chemistry

Molecular Drug Design

Experimental Pharmacology

Biophysics

Bio­medical engineering

Cell Biology

Clinical Microbiology

Pharmacoeconomics

Pharmagenomics

Proteonomics

Pharmacovigilence

Toxicology

Paleiobiology

Nutritional Sciences

Subcription 100% free Subscription There will be no subscription charges for the articles in our journal. All articles are freely accessible.

We are offering open access to everyone for all articles published by our International Research Journal ofPharmaceutical and Applied Sciences (IRJPAS), to attract more viewers. Our journals are aimed to share theknowledge and useful research outputs for global utilization. In order to save the cost of printing and publishing, our journals are available in online mode only. So, we are notproviding any hardcopies. However, we are offering free downloading and printing of published articles in our journal, foryour perusal purpose.

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Current Issue

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International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. AppSci. www.irjpas.com

Chief EditorDr. M. Chinna Eswaraiah

Managing Editors

Mr. Md. Habibur RahmanMr. A. Elumalai

12/31/2014 IRJPAS

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Home Editorial Board Instruction to Authors Manuscript Submission Archives Subcription Contact Us

Pharmaceutics

Pharmacology

Medicinal Chemistry

Pharmacognosy

Natural Chemistry

Pharmaceutical Analysis

Nanotechnology

Industrial Pharmacy

Pharmacy Practice

Novel Drug Delivery

Biopharmaceutics

Pharmacokinetics

Computational Chemistry

Molecular Drug Design

Experimental Pharmacology

Biophysics

Bio­medical engineering

Cell Biology

Clinical Microbiology

Pharmacoeconomics

Pharmagenomics

Proteonomics

Pharmacovigilence

Toxicology

Paleiobiology

Nutritional Sciences

Contact UsWe take pride and pleasure in launching International Research Journal of Pharmaceutical and Applied Sciences(IRJPAS) to furnish the needs in the areas of Pharmaceutical and Applied Sciences and explore the research globally. Editor in Chief

International Research Journal of Pharmaceutical and Applied Sciences (IRJPAS) Dr. M. Chinna Eswaraiah, M. Pharm., PhD

Principal, Anurag Pharmacy College,Kodad, Nalgonda, Andhra Pradesh, India­508206Phone: +91­98281­73650Fax: 08683­272454E­mail: editors@irjpas.com For submission of your article for publication, send your manuscript atsubmit@irjpas.com or/and irjpas@gmail.com For any other information or query please send your message or suggestion at info@irjpas.com or contactmanaging editors Mr. Md. Habibur Rahman, M. Pharm., MBA, (PhD)

Mob: +91­9014252992Email: habiburruh@gmail.com Mr. A. Elumalai, M. Pharm., (PhD)

Mob: +91­9652289364Email: malairx@gmail.com

Designed by: PHARMAWEB

Current Issue

Submit your Manuscript

International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. AppSci. www.irjpas.com

Chief EditorDr. M. Chinna Eswaraiah

Managing Editors

Mr. Md. Habibur RahmanMr. A. Elumalai

12/31/2014 IRJPAS

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International Research Journal of eISSN­2277­4149

Pharmaceutical & Applied Sciences Int. Res J Pharm. App Sci. www.irjpas.com

1. CHROMATOGRAPHIC SEPARATION FOR CILAZAPRIL AND RELATED IMPURITIES DETERMINATIONM Sarat And C Rambabu

Abstract Download No of Download=378 Pages (1­6)

2. RP­HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF OMEPRAZOLE AND CINITAPRIDE IN TABLETSN.V.M.S.Bhagavanji

Abstract Download No of Download=329 Pages (7­12)

3. THE ACUTE TOXICITY OF METHANOLIC EXTRACT OF EURYCOMA LONGIFOLIA JACK ROOTS AND HISTOPATHOLOGIC CHANGES OF RAT VITALORGANSRumaisa Dhifa Mawaddah, Firdalena Meutia, Sofia, Hanifah Yusuf

Abstract Download No of Download=337 Pages (13­17)

4. A REVIEW: ANIMAL MODELS USED IN THE SCREENING OF ANTIEPILEPTIC DRUGSKasthuri.S*, Karthigadevi.K, Manjulakshmi.P, S. Kavimani

Abstract Download No of Download=267 Pages (18­23)

5. VARIABLES EFFECTING DRUG ENTRAPMENT EFFICIENCY OF MICROSPHERES: A REVIEWKaur Dupinder*, Saini Seema

Abstract Download No of Download=377 Pages (24­28)

6. NEW DRUG DEVELOPMENT: A REVIEWDr. Anil Kumar M.H., Mr. Varun Gopinath.

Abstract Download No of Download=1678 Pages (29­37)

7. DETERMINATION OF SELENIUM CONCENTRATION IN DIFFERENT SPECIES OF RICE CONSUMED IN BANDUNG INDONESIAHolis A. Holik*, Herlianda Bianti, Mutakin, Rizky Abdulah

Abstract Download No of Download=313 Pages (38­41)

8. WITHANIA COAGULANS AND PSIDIUM GUAJAVA­ AN OVERVIEWRoshni Barad*, Purvi Soni, Miss Siddhi Upadhyay, Dr. Umesh Upadhyay

Abstract Download No of Download=458 Pages (42­47)