“FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF

CELECOXIB”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY

SATAYENDRA KUMAR

M.PHARM PART-1

DEPARTMAENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Mr. K . SENTHIL KUMAR, M.Pharm

ASSISTANT PROFESSOR

Department of pharmaceutics

Dr H.L.T College of pharmacy

Kengal, chennapatna -571502

2008
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE KARNATAKA

ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. Name of the Candidate and

SATAYENDRA KUMAR
Address (In Block Letters) M. Pharm, Part-I
DEPARTMENT OF PHARMACEUTICS
Dr. H. L. T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA-571502
BANGALORE (RURAL), KARNATAKA

2. Name of the Institution Dr. H. L.T. College of Pharmacy

Kengal, Channapatna, Bangalore (Rural) 571 502

3. Course of the Study and

Master of Pharmacy in Pharmaceutics
Subject

4. Date of Admission to the 14th Feb 2008

Course

5. Title of the Topic

“FORMULATION AND EVALUATION OF
ORODISPERSIBLE TABLETS OF
CELECOXIB ”
6. BRIEF RESUME OF THE INTENDED WORK

6.1) NEED FOR THE STUDY

Oral drug delivery remains the preferred route for administration of various drug to produce systemic effects of
drugs .Solid oral dosage forms represents the preferred class of product, as tablet represents a unit dosage form in
which one usual dose of the drug has been accurately placed. It avoids errors in the total dose to be taken when the
drug is self- administered by the patient .

Over a decade, the demand for development of orally disintegrating tablets (ODTs) has enormously increased as it has
significant impact on the patient compliance. Orally disintegrating tablets offer an advantage for populations who have
difficulty in swallowing . It has been reported that dysphagia1 (difficulty in swallowing) is common among all age
groups and more specific with pediatric,geriatric population along with institutionalized patients and patients with
nausea,vomiting and motion sickness complicaiotns 2 . ODTs with good taste and flavor increase the acceptabilily of
bitter drugs by various groups of population.

Orally disintegrating tablets are also called as orodispersible tablets, quick disintegrating tablets, mouth dissolving
tablets, fast dissolving tablets, rapid dissolving tablets, porous tablet and rapimelts . However, of all the above
terms ,United States of Pharmacopoeia (USP) approved these dosage forms as ODTs . Recently European
Pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within three minutes in
mouth before swallowing3.

United States Food and Drug Administration (USFDA) defined ODT as “ A solid dosage form containing medicinal
substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed upon the
tongue”. The disintegration time for ODTs generally ranges from several seconds to about a minute.

Orally disintegrating tablets offer all advantages of solid dosage forms and liquid dosage forms along with special
advantages, which include:
1. As ODTs are unit solid dosage forms, they provide good stability, accurate dosing , easy manufacturing, small
packaging size and easy to handle by patients. 4-7

2. No risk of obstruction of dosage form , which is beneficial for travelling patients who do not have access to water.

3. Easy to administer for pediatric, geriatric and institutionalized patients (specially for mentally retarded and
psychiatric patients)

4. Rapid disintergration of tablet results in quick dissolution and rapid absorption which provides rapid onset of
action8.

5. Medication as “ bitter pill” has changed by excellent mouth feel property produced by use of flavors and
sweeteners in ODTs.

6. Bioavailability of drugs that are absorbed from mouth pharynx and oesophagus is increased. 9-11.

7. Pregastric absorption of drugs avoids hepatic metabolism , which reduces the dose and increase the bioavailability. 12

Some NSAID have poor absorption in GI tract and some are degraded in GI fluid . So, to overcome this problem , an
effort is being made in the present work to formulate , evaluate and optimize the formulation of a Orodispersible tablet
containing an Celecoxib.
 6.2.) REVIEW OF LITERATURE

1. Allen et. al. utilized this process for preparing ODT. The ODT formulations consisted of hydrolyzed/unhydrolyzed
gelatin as supporting agent for matrix , mannitol as bulking agent and sodium starch glycolate or croscarmellose
sodium as disintegrating agent. Disintegration and dissolution were further improved by adding effervescent
components i.e. citric acid(an acid) and sodium bicarbonate (an alkali).The formulaton was spray dried to yield a
porous powder. The ODT made from this method disintergrated in <20 s 13.

2. Abdelbary et.al. prepared ODT by incorporating a hydrophilic waxy binder (super polystate) PEG -6-stearate .
superpolystate is a waxy material with an m.p of 33 -37˚C and an hydrophilic lipohilic balance of 9 .It not only acts as
a binder and increases the physical resistance of tablets but also helps the disintegration of tablets as it melts in the
mouth and solubilizes rapidly leaving no residue 14.

3. Kuno et.al. investigated the disintegration of ODT by phase transition of sugar alcohols using erythritol (m.p
122˚C) , xylitol (m.p 93-95˚C),trehalose (97˚C) and mannitol (166˚C).The tablet hardness was increased after heating
process , due to the increase of inter particle bonds or the bonding surface area in tablets induced by phase transition of
lower melting point sugar alcohol15.

4. Koizumi et.al. developed ODT utilizing camphor a subliming material that is removed from compressed tablets
prepared using a mixture of mannitol and camphor. Camphor was sublimated in vaccum at 80˚C for 30 min after
preparation of tablets16.

5. Kaushik D. et.al. have worked on the “Development of Melt in Mouth tablets by sublimation Technique” This was
indiacative of the fact that the volatile salt was completely removed from the tablets resulting in the creation of pores
in the tablets , which were responsible for the rapid disintegration of tablets in the oral cavity 17.

6. H.S.Mahajan et.al. have worked on the mouth dissolved tablets of sumatriptan succinate were prepared using
disintergrant sodium starch glycoalte, carboxy methyl cellulose, sodium and treated agar by direct compression
method. The tablets disintegrate invitro and invivo within 10 to 16 seconds and 12 to 18 seconds respectively . Almost
90% of drug was released from all formulations within 10 min 18.

6.3.) MAIN OBJECTIVES OF THE STUDY

The present work is an attempt

1. To develop Orodispersible tablet contains celecoxib drug by using special excipients like super disintegrants
alone or with combinations.

2. To evaluate for the precompression characteristics of powder mixture like bulk density , flow property , angle
of repose , compressibility index etc.

3. To evaluate the compression characteristics of the tablet like hardness, friability , disintegration , tablet
porosity , wetting time and water absorption ratio etc.

4. To carry out in vitro dissolution studies of the tablet formulation

.
5. To carry out stability studies as per ICH guidelines.
7. MATERIALS AND METHODS:
7.1) SOURCE OF DATA
The preliminary data required for the experimental study is obtained from-.
1. CD-Rom search available at National Center for Scientific Information (NCSI), Indian institute of
Sciences(IISc), Bangalore.
2. Journals
3. Analytical chemistry Books
4. Library
5. Relevant Books
6. Internet Sources
7. Scientific abstracts.

7.2 METHODS OF COLLECTION OF DATA

1. The selected drug shall be characterized and evaluated for its physicochemical properties like solubility and
compactability with excipients.
2. To identify the suitable excipients alone or in combine for further processing.
3. To carry out preformulation studies like organoleptic properties , drug-excipients interaction , bulk density ,
Tap density , porosity, angle of repose , compressibility index of the powder mixture (drug and excipients).
4. To formulate various formulation of the drug containing different ratio of the super disintegrant alone or in
combination.
5. To evaluate the compressed tablet for hardness, friability , disintegration, tablet porosity, wetting time and
water absorption ratio, etc
6. The data so obtained will be subjected for statistical analysis .

7.3) Does the study require any investigation to be conducted on patients/Humans/animals? If so, please describe
briefly .
NO
7.4) Has ethical clearance been obtained from your institution in case of 7.3

NOT APPLICABLE
8) LIST OF REFERENCES
1. Lindgren S, Janzon L. Dysphagia: prevalence of swallowing complaints and clinical finding .Med Clin North
Am 1993:77:3-5.
2. Sastry SV, Nyshadham JR, Fix JA, Recent technological advances in oral drug delivery:A review . pharm Sci
Technol Today 2003;3:138-45.
3. Fu Y, Yang S , Jeong SH. , Kimura S , Park K. Orally fast disintegrating tablets: Development , technologies,
taste-masking and clinical studies. Crit Rev Ther Drug Carrier Sys 2004;21:433-76.
4. Seager H. Drug-delivery products and the zydis fast-dissolving dosage form J.pharm pharmacol 1998;50;
375-82.
5. Habib W., Khankari RK, Hontz J. Fast-dissolve drug delivery systems. crit Rev. Ther. Drug Carrier Sys
2000;17:61-72.
6. Dobetti L.Fast disintegrating tablets. US Patent 2003;6:596,311.
7. Brown D. Orally disintegrating tablets-taste over speed .Drug Del tech 2003;3:58-61.
8. Behnke K, Sogaard J, Martin S , Bauml J , Ravindran AV, Agren H, et al. Mirtazapine orally disintegrating
tablet versus sertraline: A prospective onset of action study. J clin Psychopharmacol 2003;23:358-64.
9. Jaccard TT , Leyder J.Une nouvelle forme galenique le lyoc. Ann Pharm Fr 1985;43: 123-31
10. Dollo G, Chevanne F, Le Corre P, Chemtob C, Le verge R, Bioavailibility of phloroglucinol in man .J pharm
Belg 1999;54:75-82.
11. Gafitanu E, Dumistracel l. Antochi S , Formulations and bioavailability of propyphenazone in lyophilized
tablets . Rev Med Chir Soc Med Nat lasi 1991;95:127-8.
12. Clarke A , Brewer F., Johnson ES, Mallard N , Hartig F, Taylor S, et al .A new formulation of selegiline :
Improved bioavailability and selectivity for MAO -B inhibition. J Neural Transm 2003;110:124-5.
13. Allen LV. Wang B. Process for making a particulate support matrix for making a rapidly dissolving tablet .
US patent 5,587,180;1996.
14. Abdelbary G., Prinderre P,Eouani C, Joachim j, Reynier JP, Piccerelle P. The preparation of orally
disintegrating tablets using a hydrophilic waxy binder .Int J Pharm 2004:278;423-33.
15. Kuno Y, Kojima M, Ando S, Nakagami H, Evaluation of rapidly disintegrating tablets manufactured by phase
transition of sugar alcohols. J control Release 2005;105:16-22.
16. Koizumi K, Watanabe Y, Mortia K , Utoguchi N , Matsumoto M. New method of preparing high porosity
rapidly saliva soluble compressed tablets using mannitol with camphor; A subliming material .Int J pharm
1997:152;127-31.
17. Kaushik D , Saini TR and Dureja H “ Development of melt in mouth tablets by sublimation technique ”
Journal of pharmaceutical research vol- 3, No- 2, April,12004 page no 35-37 .
18. H.S. Mahajan , B.S.Kuchkar and A.C. Badhan , “mouth dissolving tablets of sumatriptan succinate ”Indian
journal of pharmaceutical science , March – April 2004 , page no 238 – 240.
9. Signature of the candidate
10. Remarks of the Guide
Topic selected for Dissertation work is satisfactory.
This can be carried out in our Laboratory.
11. Name and Designation of
(In Block Letters) Mr.K. SENTHIL KUMAR M.Pharm.
ASSISTANT PROFESSOR,
11.1 Guide DEPT OF PHARMACEUTICS

Dr. H.L.T. COLLEGE OF PHARMACY,

KENGAL, CHANNAPATNA- 571 502
BANGALORE (RURAL), KARNATAKA.

11.2 Signature

11.3 Co-Guide (If any)

---------------

11.4 Signature
11.5 Head of the Department
Mr.RAVADA RAMESH, M.pharm
PROFESSOR,
DEPT. OF PHARMACEUTICS,
Dr. H.L.T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
BANGALORE (RURAL), KARNATAKA.
11.6 Signature
12 12.1 Remarks of the The selected topic is satisfactory. The Dissertation
Chairman and Principal work is feasible in our Laboratory.

12.2 Signature

Principal, Dr, H.L.T. College of Pharmacy

Kengal, Channapatna.

From
SATAYENDRA KUMAR M.Pharm Part-1
 DEPARTMENT OF PHARMACEUTICS
Dr. H.L.T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA,
BANGALORE (RURAL)-571 502.

To
THE REGISTRAR (EVALUATION),
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA BANGALORE
4TH “T” BLOCK, JAYANAGAR,
BANGALORE-560 041.

(THROUGH PROPER CHANNEL)

SUB : SUBMISSION OF SYNOPSIS OF DISSERTATION.

RESPECTED SIR,

HEREWITH, I AM SUBMITTING SYNOPSIS OF DISSERTATION WORK “FORMULATION AND

EVALUATION OF ORODISPERSIBLE TABLETS OF CELECOXIB ” FOR REGISTRATION IN
M.PHARM. (PHARMACEUTICS) OF RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA BANGALORE.

KINDLY ACCEPT THE SAME AND OBLIGE.

THANKING YOU,
YOUR’S FAITHFULLY,

Place : Channapatna. (SATAYENDRA KUMAR)

Date :
GUIDE :
Mr.K. SENTHIL KUMAR M.Pharm
ASSISTANT PROFESSOR PRINCIPAL
DEPT. OF PHARMACEUTICS DR.H.L.T. COLLEGE OF PHARMACY
DR. H.L.T. COLLEGE OF PHARMACY CHANNAPATNA.
CHANNAPATNA.