1. 1SHODH, SAMIKSHA AUR MULYANKAN
International Indexed & Refereed Research Journal, ISSN 0974-2832,(Print) E- ISSN-2320-5474, December,2013, VOL-V * ISSUE- 59
Introduction
The concept of Mouth Dissolving Drug
Delivery System emerged from the desire to provide
patient with more conventional means of taking their
medication. It is difficult formanypatients to swallow
tablets and hard gelatin capsules. Hence they do not
comply with prescription, which results in high
incidence of non-compliance and ineffective therapy.
In some cases such as motion sickness, sudden
episodes of allergic attacks or coughing and
unavailabilityofwater,swallowingconventionaltablets
maybedifficult.Particularlythedifficultyisexperienced
by pediatric and geriatric patients. Such problems can
be resolved by means of Mouth Dissolving Tablet.
When put on tongue, this tablet disintegrates
instantaneously, releasing the drug, which dissolves
or disperses in the saliva. Some drugs are absorbed
from the mouth, pharynx and esophagus as the saliva
passes down into the stomach. In such cases,
bioavailabilityofdrugissignificantlygreaterthanthose
observed from conventional tablet dosage form.
MDTsdisintegrate and/ordissolve rapidlyin
the saliva without the need for water. Some tablets are
designed to dissolve in saliva remarkably fast, within
a few seconds, and are true fast-dissolving tablets.
Others contain agents to enhance the rate of tablet
disintegration in the oral cavity, and are more
appropriatelytermedfast-disintegratingtablets,asthey
may take up to a minute to completely disintegrate.
When put on tongue, this tablet disintegrates
instantaneously, releasing the drug, which dissolves
or disperses in the saliva. Some drugs are absorbed
from the mouth, pharynx and esophagus as the saliva
passes down into the stomach. In such cases,
bioavailabilityofdrugissignificantlygreaterthanthose
observedfromconventionaltabletdosageform.MDTs,
as a novel dosageform, have several characteristics to
Research Paper -Pharmaceutical Science
December , 2013
Formulation andEvaluationofMouthDissolving
Tablets of Ondansetron HCL.
* Rohit Singh Parihar
*InstituteofPharmaceuticalscienceandresearchcentre,BhagwantUniversity,Ajmer,India
A B S T R A C T
Ondansetron used in the treatment of prevention of nausea and vomiting associated with emetogenic cancers chemotherapy,
postoperation, and radiation. It shows low bioavailability due to high hepatic first pass metabolism and protein binding.
Hence the present work was undertaken to formulate mouth dissolving tablets of Ondansetron with an objective -
* To Improve and enhance bioavailability.
* To avoid first pass effect by administering the drug through mouth.
* To improve therapeutic efficacy and patient compliance.
distinguishthemfromthemoretraditionaldosageforms.
Taste-maskingisofcriticalimportanceintheformulation
of an acceptable MDT. Traditional tablet formulations
generally do not address the issue of taste masking,
because it is assumed that the dosage form will not
dissolve until passing the oral cavity. Many oral
suspensions, syrups, and chewable tablets simply
contain flavors, sugars and other sweeteners to
overwhelm or complement the bitter taste of the drug.
Current methods of taste masking in fast dissolving/
drug particles.
MDTs are the disintegrating tablets include
sweeteners and flavors; however, these are not a
sufficient means for taste-masking many bitter drugs.
Most of the MDT technologies incorporate unique
formsoftastemaskingaswell.Theprimarymethodsof
taste-maskingincludeadsorptionontoorcomplexation
with carriers and spray coating of solid dosage forms,
whichincreaseconsumerchoice,forthereasonofrapid
disintegrate/dissolve in oral cavity within seconds and
swallowed without the need of water or chewing. As
tablet disintegrates in mouth this could enhance the
clinical effect of the drug through pre-gastric absorp-
tion from the mouth, pharynx and esophagus. This
leads to an increase in bioavailability by avoiding first
pass metabolism.
DifficultiesWithExisting OralDosageForm
1) Patient may suffer from tremors therefore they have
difficulty to take powder and liquids. In dysphasia
physical obstacles and adherence to an esophagus
may cause gastrointestinal ulceration.
2) Swallowing of solid dosage forms like tablet and
capsules and produce difficulty for young adult of
incomplete development of muscular and nervous
system and elderly patients suffer from dysphasia.
3) Liquid medicaments (suspension and emulsion) are
packed in multidose container; therefore achieve

2. 2 SHODH, SAMIKSHA AUR MULYANKAN
International Indexed & Refereed Research Journal, ISSN 0974-2832,(Print) E- ISSN-2320-5474, December,2013, VOL-V * ISSUE- 59
ment of uniformity in the content of each dose may
bedifficult.
4) Buccalandsublingualformationmaycauseirritation
to oral mucosa, so patients refused to use such
medications
5) Cost of products is main factor as parenteral formu
lations are most costly and discomfort.
Advantages of Fast Dissolving Drug Delivery System
FDDTs
Fast dissolving technology offers:
1) Improved compliance/added convenience.
2) No water needed.
3) No chewing needs.
4) Better taste.
5) Improved stability.
6) Suitableforcontrolled/sustainedreleaseactives.
7) Allows high drug loading.
8) Ability to provide advantages of liquid medica
tion in the form of solid preparation.
Drug Profile
Ondansetron Hydrochloride Dihydrate Proprietary
name: Zofran; Zophren. IUPAC Name: 1,2,3,9-
Tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-
yl)methyl]4Hcarbazol-4-onehydrochloridedehydrate
Molecularformula:C18H19N3O,HCl,2H2O
Molecularweight:365.9
Structure:
Volumeofdistribution
Approx. 140 to 160 L; also reported as 1.3 to 2.9 L/kg.
3.05L/kg(mildliverdisease);
3.36 L/kg (moderate); 3.86 L/kg (severe); 2.5 L/kg
(healthy individuals).
Clearance
16.6 L/h (patients with mild liver disease); 15.9 L/h
(moderate liver disease); 11.6 L/h
(severe); 28.3 L/h (healthy volunteers).
Distributioninblood
Blood:plasma ratio is 0.83. It distributes into erythro-
cytes and circulates bound
within.
Protein binding
70 to 75%.
Dose
Adult:8mg(orally)beforetreatmentfollowedby8 mg
every12h.16mgdaily(byrectumadministration)or32
mg(intravenously).Children:5mg/m2(intravenously)
immediatelybeforetreatmentandthen4mgorallyevery
12 h.Alternatively, 100 g/kg (maximum 4 mg) (over 2
years old).
MechanismofAction:
Ondansetron is a selective serotonin 5-HT3
receptorantagonist.Theantiemeticactivityofthedrug
is brought about through the inhibition of 5-HT3 re-
ceptors present both centrally (medullary chemore-
ceptorzone)andperipherally(GItract).Thisinhibition
of5-HT3receptorsinturninhibitsthevisceralafferent
stimulation of the vomiting center, likely indirectly at
the level ofthe areapostrema, aswellas through direct
inhibitionofserotoninactivitywithintheareapostrema
and the chemoreceptor trigger zone
Evaluation of Fast Mouth Dissolving Tablets of
Ondansetron Hydrochloride:-
A) Precompression Parameters.
a) Percentage yield.
b) Carr's Index & hausner's ratio.
c) bulk Density.
d) Angle of repose.
(B) Post compression Parameters
a) Thickness of Tablets
b) Taste, Colour, Odour of Tablets
c) Hardness and Friability of Tablets
d) Wetting time of Tablets
e) Moisture Uptake by Tablets
(C) DrugcontentandReleasestudies
a) Assay of Pooled Sample of Tablets
Description
A white crystalline solid from water/isopro-
panolwithm.p.178.5°to 179.5°.Itis
soluble in aqueous solutions but solubility decreases
withpH>5.7.
Dissociation Constant.
Hydrochloride dihydrate; pKa7.4.
Bioavailability
60% (young healthy subjects), 65% (elderly); 85%
(patients with cancer) and 100%
(severe hepatic impairment).
Half-life
3 hour (young healthysubjects), 5 h (elderly)
and 15 to 32 h (severe hepatic impairment).
Evaluation Of Mdt Of Ondansetron Hydrochloride Precompression Parameters:-
S.no Parameters F1 F2 F3 F4 F5
1) Bulk Density 0.47 ± 0.01 0.453 ± 0.01 0.456 ± 0.05 0.436 ± 0.02 0.463 ± 0.01
2) Tapped Density 0.58 ± 2.6 0.556 ±0.01 0.543 ± 0.01 0.536 ± 0.03 0.53 ± 0.02
3) Carr's Index 18.68 ± 2.6 18.41 ± 3.83 16.5 ±1.38 14.2 ± 3.23 12.56 ± 0.73
4) Hausner Ratio 1.118 ± 0.004 1.227 ± 0.05 1.19 ± 0.022 1.07 ± 0.04 1.14 ± 0.01

3. 3SHODH, SAMIKSHA AUR MULYANKAN
International Indexed & Refereed Research Journal, ISSN 0974-2832,(Print) E- ISSN-2320-5474, December,2013, VOL-V * ISSUE- 59
Evaluation of Thickness of MDT Formulations of Ondansetron
Hydrochloride.
S.no Formulation Thickness In Mm ± Sd
1) F1 3.0 ± 0.225
2) F2 2.9 ± 0.321
3) F3 3.1 ± 0.214
4) F4 3.0 ± 0.521
5) F5 3.0 ± 0.331
* Each value is an average of 6 determinations
Table : Results of Evaluation of Hardness and Friability of
MDT Formulations of Ondansetron Hydrochloride.
S.no Formulation Hardness Friability
1) F1 2.830 ± 0.258 0.2819 ± 0.023%
2) F2 2.710 ± 0.248 0.139 ± 0.012%
3) F3 2.580 ± 0.258 0.205 ± 0.0134%
4) F4 2.630 ± 0.288 0.067 ± 0.0312%
5) F5 2.460 ± 0.197 0.139 ± 0.0243%
* Each value is an average of 6 determinations
Table : Results of Evaluation of Wetting time of MDT
Formulations of Ondansetron Hydrochloride.
S.no Formulation Wetting Time ± Sd
1) F1 40
2) F2 50
3) F3 36
4) F4 30
5) F5 85
* Each value is an average of 6 determinations
Table 10 : Results of Evaluation for Assay of MDT of Ondansetron Hydrochloride
S.no Parameters F1 F2 F3 F4 F5
1) Drug contents 100.34% 102.45% 103.50% 102.41% 102.87%
b) Weightvariation and UniformityofDrugcontent
c) In vitro Disintegration Time
e) In-vitro Dissolution Studies
Result
See Table 1
Table : Results of Evaluation for Weight Variation of MDT Formulations of Ondansetron Hydrochloride.
S.no Formulation Average Weight of One Tablet % Weight Variation Range
1) F1 152 mg 161.25 - 138.75 mg
2) F2 150 mg 161.25 - 138.75 mg
3) F3 152 mg 161.25 - 138.75 mg
4) F4 145 mg 161.25 - 138.75 mg
5) F5 150 mg 161.25 - 138.75 mg
S.no Formulation Sample %Drug Content (W/W) Complies With I.p Limits
1) F1 5 tablets 100 - 102% 90 -110%
2) F2 5 tablets 100 -103% 90 -110%
3) F3 5 tablets 100 - 103% 90 -110%
4) F4 5 tablets 98 - 103% 90 -110%
5) F5 5 tablets 98 - 103% 90 -110%
Table : Results of Evaluation for Uniformity of Content of FMDT Formulations of Ondansetron Hydrochloride.
see table 1
Table : Results of Evaluation of in vitro Disintegration Time MDT of Ondansetron Hydrochloride.
S.no Parameter F1 F2 F3 F4 F5
1) Disintegration time 25 sec 45 sec 19 sec 17 sec 60 sec
* Each value is an average of 6 determination
Post Compression Parameters:-
See Table 2 ,Table -3
See Table 4
See Table 10
See Table
Discussion
In the present study, a total of five formu-
lations of Mouth Dissolving Tablets of Ondansetron
HydrochloridewerepreparedusingSuperdisintegrant
Addition Method.
In order to select the best formulation,
various parameters were checked and subjected to
in vitro dissolution studies, and their release profile
was observed and compared. Evaluation forGen-
eral appearance, Physical parameters, Drug content
and Release studies were performed according to
official methods and also with modified official
methods.All the above tests were described in Meth-
odology Section.
Conclusion
The Mouth Dissolving Tablets of
Ondansetron Hydrochloride were prepared by Direct
compression method by using superdisintegrant addi-
tion.Atotalof5batcheswereprepared.Differentbatch
having different disintegrating agent.
All the Mouth Dissolving Tablets formula-
tion prepared were evaluated for general appearance
and physical parameters, Drug content and release
studies.Thetablettingpropertiesofalltheformulation
were found to be within the standard limits. All the
Mouth Dissolving Tablets formulations get dispersed
withinatimeperiodof3minuteswhentestedforinvitro

4. 4 SHODH, SAMIKSHA AUR MULYANKAN
International Indexed & Refereed Research Journal, ISSN 0974-2832,(Print) E- ISSN-2320-5474, December,2013, VOL-V * ISSUE- 59
disintegration. All the physical characterstics of the
formulationslikethickness, Hardness,Friability,Wet-
ting time, Assay value, Drug content, In vitro release
property after disintegration and during in vitro disso-
lutionstudywerefound to be wellwithin thelimits and
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4) Kuchekar B.S., Badhan A.C.and Mahajan H.S. "Mouth Dissolving Tablets: A Novel Drug Delivery System",Pharma Times,
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5) Wilson C.G., Washington N., Peach J., Murray G.R. andKennerley J.; "The behavior Indurwade N.H. , Rajyaguru T.H. and
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Fast Dissolving Tablets of ondansetron Hcl.206Journal of Pharmacy Research Vol.1.Issue 2.Oct-December 2008 publi
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R E F E R E N C E
Table: Results of Evaluation for in vitro Drug Release afte r Dispersion of
MDT Formulations of Ondansetron Hydrochloride.
S.no Formulation In Vitro Disintegration % DR% Drug Release After Dissolution
1) F1 25 seconds 90.0315 ± 2.1131%
2) F2 45 seconds 88.0564 ± 3.211%
3) F3 19 seconds 92.0215 ± 1.892%
4) F4 17 seconds 94.0340 ± 2.189%
5) F5 60 seconds 85.650 ± 2.168%
* Each value is an average of 6 determinations.
official standards. Mouth Dissolving Tablets prepara-
tion requires specialized packing aqnd storage in con-
trolled humidity condition.
Table: In vitro Dissolution Profile Data for FMDT Formulations of Ondansetron Hydrochloride.
Formulation code Percentage Drug release* ±SD of FMDT of Terbutaline Sulphate at the following time intervals
Formulation code 3 minutes 6 minutes 9 minutes 12 minutes
F1 79.6671 ± 2.8130% 81.5828 ± 1.1129% 86.6740 ± 1.1029% 90.0315 ± 2.1131%
F2 76.6602 ± 0.9895% 80.6694 ± 2.9613% 84.6786 ± 4.1994% 89.5034 ± 3.2110%
F3 76.6860 ± 1.4248% 82.6186 ± 3.2416% 88.8064 ± 4.1428% 92.0215 ± 1.8923%
F4 79.2582 ± 2.2614% 86.6832 ± 3.1020% 90.6924 ± 4.9184% 94.0340 ± 2.1894%
F5 75.2582 ± 2.2614% 79.6832 ± 3.1020% 81.6924 ± 4.9184% 85.6580 ± 2.1680%