FORMULATION AND EVALUATION OF
SUPERDISINTEGRANT TABLETS OF SERTRALINE
HYDROCHLORIDE
PRESENTED BY GUIDED BY
• KAJAL PATEL • MR.RAJESH PALVA
• KHASIYA JIGNA ASSISTANT PROFESSOR
• ZEEL BAROT (M.PHARM)
• MAHMED SAHIL
MALIK
• ANKITA RAINA
A.R. COLLEGE OF PHARMACY & G.H PATEL INSTITUTE OF PHARMACY
VALLABH VIDHYANAGAR 388-120
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CONTENT
S.NO TABLE OF CONTENTS
1 INTRODUCTION
2 AIM AND PLAN OF THE WORK
3 LITERATURE REVIEW
4 DRUG PROFILE
5 EXCIPIENT PROFILE
6 DISEASE PROFILE
7 MATERIALS AND METHODS
8 PROCEDURE
9 FORMULATION DEVELOPMENT
10 EVALUATION OF TABLETS
11 RESULTS AND DISCUSSION
12 SUMMARY AND CONCLUSION
13 REFERENCE
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Defination of orodispersibletablets1,2,3,4
❖Europrsn pharmacopiea described orally disintegrating tablets as- Uncoated
tablets intended to be placed in the mouth where they disperse rapidly
before being swallowed and tablet which shouid disintegrate within 3
minutes
❖when the drug 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, bioavailability of drug is
significantly greater than those observed from conventional tablet dosage
form.
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Tablets and capsules are the most popular dosage form but most important
draw bake of such dosage form is “dysphasia” or “difficulty in swallowing”.
This disorder is also associated with a number ofconditions like:
Parkinsonism
Motion sickness
Reasons of
M aking Unconsciousness
Orodispersible
Tablets5
Elderly patients
Children
Mentally disable person
Unavailability of water
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It estimated that 50% of population suffers this problem, which result in high
incidence of noncompline and ineffective therapy and need of the drugs is increases.
Drugs which are having a short half-life and needs frequent dosing.
A drug having bitter or either having unacceptable taste whose taste masking cannot
be achieved.
A preparation require control or sustain release are in appropriate form Orodispersible
drugs.
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❖ Excipients For Orodispersible Tablets:6,7
• Excipient used in
Orodispersible tablets Name of the excipients Percentage
contain one super used
disintegrant, a diluent or
bulking agent, a lubricant and Super disintegrants 1-15%
optionally swelling agent a Binder 5-10%
permeabilizing agent
Antiseptic agent 0-10%
sweetners and flavorings
agents. diluents 0-85%
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❖ Importance of superdisintegrants7,8,9,10
• These conventional tablets are intended to be swallowed whole and
desired to disintegrate, release the medicaments for dissolution and
providing therapeutic efficacy rapidly in the gastrointestinal track
• As disintegration plays an important role in development of solid oral,
formulator give special emphasis on selection of disintegrant in doses
system. Disintegrants are substance of mixture of substances added to the
drug formulation which facilated dispersion or breakup of tablet content
of capsule inttp smaller particles for quickdissolution.
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• Natural and synthetic superdisintegrants like mucilage, cross linked
carboxymethyl cellulose (croscarmellose) sodium starch glycolate, poly vinyl
pyrrolidone are used to provide immediate disintegration of tablets and facilitate
the design of delivery system with desirable characteristics.
• These types of formulations are widely recommended for the drugs used in
emergency .
• Disintegrants are substancesor mixture of substancesadded to the drug
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❖ Ideal property of superdisintegrants11
• It should havegood
• It should produce
particle size, good • It should havepoor •It should produce
good moulding and compactable less
hydration capacityand water solubility.
flow property. friable tablets.
compressibility
•Effective at very low
•It should haveno
concentration and
• Nontoxic and should tendency to form
should havegreater
disintegrating have good mouthfeel. complexes with the
drugs.
efficiency.
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❖ Advantages OfSuperdisintegrants7,8
• Compatible with
• Remarkable tendency on commonly used therapeutic
• No lump formation on agents and excipients. • • Effective in lower
wetting causing
disintegration.
rapid disintegration. Does not stick to the concentrations.
punches anddyes.
•Some are anionic and may
• Less effect on
• More effective cause some slight in vitro
compressibility and flow
intragranular. binding with cationic drugs.
ability
Biodegradable.
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• Expensive.
❖ Disadvantages
• Time consuming and fragile.
OfSuperdisintegrants10
• More sensitive
and hygroscopic in nature.
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❖Types of superdisintegrants
NATURAL SYNTHETIC
SUPERDISINTEGRANTS SUPERDISINTEGRANTS
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❖ Natural
superdisintegrants
1. Ispaghula husk
mucilage(plantagoovat
a)
2. Xanthan gum
3. Gellan gum
4. Chitin
5. Locust bean gum
6. Mango peel pectin
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Ispaghula husk mucilage (plantagoovata)
Consist dried seed known as-plantagoovata
which present in epidermisof seed.
Material squeezed through muslin
Seed soakedin disstilledwater Mucillage have featuers
clothfor filteringand seaprating.add
then boiled for complete release like=binding,disintegrating,sustaini
acetone to filtrate so precipitate
of mucillageintowater. ng properties
mucilage,drieditless than60c
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Synthetic
superdisintegrants15,16
1. Modified stach(sodium starch
glucolate,primojel)
2. Cross-linked polyvinyl pyrrolidone
3. Modified cellulose(croscarmellose
sodium)
4. Microcryustalline cellulose(avicel)
5. alignates
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Modified starch (sodium starchglycolate)16
• Modified Starch (Sodium starch glycolate, Primojel)Sodium starch glycolate is the sodium
salt of a carboxymethyl ether of starch.
• These are modified starches made by crosslinking of potato starch as it gives the product with
the best disintegrating properties.
• The degree of cross-linking and substitution are important factors in determining the
effectiveness of these materials as superdisintegrant. The effect of the crosslinking is to
reduce both the water-soluble fraction of the polymer and the viscosity of dispersion in water.
The natural pre dried starches swell in water to an extent of 10-20 percent and the modified
starches increase in volume by 200-300 percent inwater.
• The mechanism by which this action takes place involves rapid absorption of water leading
to an enormous increase in volume of granules that result in rapid and uniform disintegration.
19,22The tablets formulated by using these superdisintegrants may disintegrate in
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❖ Mechanism of action of
superdisintegrants17,18,19
•Porosity and
• Combination
• Swelling. capillary action
action.
(wicking).
• Enzymatic
• Heat of wetting. • Deformation.
reaction.
• Electrostatic
• Chemical reaction
repulsion.
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swelling
Swelling is widely accepted mechanism and necessarily the first step
for tablet disintegration. It is a process in which certain disintegrating
agents (such as starch)generate the disintegrating effect.
Tablets with high porosity showpoor disintegration due to lack of
adequate swelling force.
Particles of disintegrants swells when it comes in contact with water,
the adhesiveness of other pharmaceutical ingredients present in a
tablet can be overcome which causes the tablet toBreak.1
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Porosity and capillaryaction(wicking)
• Disintegrating agents which does not swell, act by the
mechanism of porosity and capillary action. Porosity of the
tablet produce pathways for the fluid penetration into
tablets.
• When we put the tablet into suitable aqueous medium, the
medium penetrates into the tablet and replaces the air
adsorbed on the particles, which weakens the
intermolecular bond and breaks the tablet into fine
particles.
• Water uptake by tablet depends upon hydrophilicity of the
drug/excipient and on
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Porosity and capillaryaction(wicking)
• Liquid is drawn up or “wicked” into this pathway through
capillary action and break the bonding of inter particles
which causes the tablet to break apart. For these types of
disintegrants maintenance of porous structure and low
interfacial tension towards aqueous fluid is necessary
which helps in disintegration by creating a hydrophilic
network around the drug particle
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Deformation
and electric
repulsion
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❖ Techniquesused in thepreprationof
superdisintegrantstablets20,21,22
Click to add text
Molding Sublimation Spray
drying
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Molding
Compressing Vacuum Heatmolding
molding lyophylization process
• Moistening • Evaporation • Agar solution
the powder of solventat as abinder
blend with standard and blister
hydrochloric pressure packaging
solvent mold and
• Pressing into dring.
mold plates
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Sublimation
• The presence of a porous
structure in the tablet matrix.
Conventional compressed
tablets that contain highly
water-soluble ingredients often
fall to dissolve rapidly because of
low porosity of the matrix.
Hence. To generate porous
matrix, volatile ingredients are
used that are later subjected to
a process of sublimation.
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Spraydrying
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❖ AIM:
• The Aim of the present work is to improve the Bioavailability of sertraline by
Preparing fast disintegrating tablet of sertraline by direct compression technique.
• Sertraline Hydrochloride is an antidepressant of the selective serotonin reuptake
inhibitor (SSRI) class. The mechanism of action of Sertraline is presumed to be
linked to its inhibition of CNS neuronal uptake of serotonin (5HT). SHC is white
crystalline powder that is slightly soluble in water and isopropyl alcohol and
sparingly soluble in ethanol. So, it undergoes extensive first pass metabolism and
having oral bioavailability of 44%, thus, suitable candidate for Fast Dissolving
Systems.
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• Sertraline HCL is BCS CLASS II Drug (poorly water soluble) leading to less
solubility and after oral administration it extensive undergoes first pass metabolism
which reduce the overall bioavailability of drug,
• To overcome this drawback, the present investigation is concerned with the
development of fast dissolving tablets of sertraline HCL by using different types of
superdisintegrants such as cross povidone, microcrystalline cellulose are available,
Amongst this we have used MCC (Avicel PH 102), Kyron T-134 to reduce the
disintegration time and improved the Bioavailability.
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• The present study has been undertaken with following objectives;
1) To prepared fast disintegrating tablet of sertraline by direct compression
2) To evaluate various parameters of prepared tablet and to compare in vitro dissolution
profile with that of marketed product.
3) To improve the bioavailability by improving disintegration time and dissolution time.
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❑ Literature Review
Sr. No. Title of Paper Authors/Inventors Journal Details Objectives of Study Major Findings of the study/Work
1 Formulation design and Gohel M., Patel M., Amin American Association The results of multiple linear regression The tablets were evaluated for % friability,
optimization of mouth dissolve A., Agrwal R., Dave R. and of pharmaceutical analysis revealed that for obtaining a wetting time and disintegration time. In
tablets of nimesulide using Bariya, N. scientists rapidly disintegrating dosage form, the present investigation a 32 full factorial
vaccum drying technique tablets should be prepared using design was used to investigate combined
optimum concentration of camphor and effect of two formulation variables:
higher percentage of crospovidone. amount of camphor and amount of
superdisintegrant.
2 Formulation and optimization Omaima A. Sammour, American Association The obtained results showed that The purpose of the present
of mouth dissolve tablets Mohammed A. Hammad, of pharmaceutical dispersion of the drug in the polymer investigation was to increase the solubility
containing rofecoxib solid Nagia A. Megrab and scientists considerably enhanced the dissolution and dissolution rate of Rofecoxib by
dispersion. Ahmed S. rate. the preparation of its solid dispersion with
Zidan. polyvinyl pyrrolidone K30 (PVP K30)
using solvent evaporation method.
3 A compaction process to Shawn A. Mitchell, Thomas International Journal of The mechanism for dissolution The purpose of this
enhance dissolution of poorly D. Reynolds and Tina P. Pharmaceutics enhancement is believed to be a study was to develop a technique to
water soluble drugs using Dasbach microenvironment to HPMC surfactant enhance the dissolution rate of poorly water
hydroxypropyl methylcellulose. effect facilitated by keeping the HPMC & soluble drugs with low-viscosity HPMC
drug particles in close proximity during without the use of solvent or heat
drug dissolution. addition.
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❑ Literature Review
Sr. No. Title of Paper Authors/Inventors Journal Details Objectives of Study Major Findings of the study/Work
4 Rapidly disintegrating Mishra D. N., Bindal M., Singh S. Indian drug dellivery All formulation showed The poor aqueous solubility of the drug
tablets of valdecoxib. K. and Kumar S. G. V., disintegration time of less than 60 results in variable dissolution rate and
seconds along with rapid in vitro poor bioavailability. In the present,
dissolution. All the formulation showed invention tablets were prepared using
more than 70 % dissolution in 30 min. various superdisintegrant following direct
compression.
5 New method of preparing Kei-ichi Koizumi, Yoshiteru International Journal A high porosity was achieved due to Compressed tablets of Mannitol did not
high-porosity rapidly saliva Watanabe, Kumiko Morita, Naoki of Pharmaceutics formation of many pores due to dissolve in water due to the low porosity.
soluble compressed tablets Utoguchi and Mitsuo Matsurnoto camphor sublimation. The compressed To increase the porosity of tablets
using mannitol with tablets have high porosity sublimation was done. Tablets were
camphor, a subliming (approximately 30%) rapidly dissolved prepared by direct compression
material within 15 seconds in saliva. containing mannitol and camphor.
6 Fast disintegrating tablets of Shirwaiker A. A. and Ramesh M. Indian Journal of Formulation containing 10 % Ac-Di-Sol The preparation contained an active
Atenolol by dry granulation Pharmaceutics showed the least disintegration time of ingredient, sugar (mannitol),
method. 30 ± 2 seconds compare to Explotab superdisintegrants and dicalcium
and Polyplasdone XL. phosphate. Required quantities of each
ingredient were weighed, mixed and
prepared the tablets by dry granulation.
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❖ EXPERIMENTAL WORK:
1. Material:
• All the glass apparatus used were of the borosilicate glass and
other reagents and solvents used were of analytical grade.
Materials/Reagents Company
•
Sertraline HCL DRL
Kyron T134 Chemdyescoorp.
MCC Chemdyescoorp.
Mg stearate Chemdyescoorp.
Aspartame Chemdyescoorp.
Talc Chiti chem
PEG-6000 ChemdyesCoorp.
Mannitol Astron chemicals
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I. SERTRALINE (DRUG)
Generic Name: Sertraline hydrochloride
Structure:
Sertraline hydrochloride
Chemical Names: cis-( lS,4S)-N-rnethyl-4-(3,4-dichlorophenyl)- 1,2,3,4- tetrahydro- 1 –
naphthalenamine hydrochloride
Molecular Formula and Molecular Weight
Molecular formula Molecular weight
Sertraline C17H17NCl2 306.2
Sertraline hydrochloride C17H18NCl3 342.7
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▪ Instruments:
Equipment’s Model/Company
Electronic analytical balance Shimadzu Corporation, Japan
Magnetic stirrer Remi Equipment, Mumbai
Hot air oven Micro Teknik, Ambala cant.
Tablet Compression machine Rimek, RSB-4 Mini Press
Hardness tester Monsanto
Friability test apparatus Almicro
Dissolution apparatus Veego
U.V. Visible Spectrophotometer UV-1800 shimadzucorporation, japan
Vernier Caliper Mitutoyo
Disintegration Tester Erection and Instrumentation engineers
Digital ultrasonic sonicator APL CD-4820
Digital pH meter Systronics 802
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Methods:
Melting point of sertraline HCL:243-249 °C
The melting point can be determined by introducing a tiny amount of drug into capillary tube,
attaching this to the stem of a thermometer center in a heating bath, heating the bath slowly and
observing the temperature at which melting begins and is complete.
Spectrophotometric analysis for Sertraline Hydrochloride:
Preparation of Standard Sertraline Hydrochloride Stock Solution ( 100µg/mL)
A 25 mg weighed and transferred to 25 mL volumetric flask. 10 mL of 0.1 M Hydrochloric Acid
(HCl) was transferred to volumetric flask and sonicated for 10 min. The Flask was shaken and
volume was made up to the mark with 0.1 M HCl to give a solution containing 100 µg/mL Sertraline
Hydrochloride.
Determination of UV Absorption maxima.
Standard Stock solution of Sertraline Hydrochloride was scanned for absorption between 200 – 400
nm by means of double beam UV Visible spectrophotometer. Sertraline Hydrochloride exhibited UV
absorption maxima at 266 nm.
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Preparation of calibration curve for Sertraline Hydrochloride (10 –
50 µg/mL) 76
• Hydrochloric acid, xM: Solutions of any molarity xM prepared by diluting
85xM ml of hydrochloric acid to 1000 ml with water.Take 25mg of sertraline
(API) and dissolve it in 25ml HCL; 1mg/ml (1000 microgram per ml).
• Stock solution: Take 2.5 ml from above solution in 25ml HCL (100 microgram
per ml).
• DILUTION:
• Take 1ml from stock solution and dilute it in 10ml of HCL; 10ppm
• Take 2ml from stock solution and dilute it in 10ml of HCL; 20ppm
• Take 3ml from stock solution and dilute it in 10ml of HCL; 30ppm
• Take 4ml from stock solution and dilute it in 10ml of HCL; 40ppm
• Take 5ml from stock solution and dilute it in 10ml of HCL; 50ppm
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• Dissolution Studies:77
• The release rate of sertraline hydrochloride from fast dissolving tablet was determined using USP
dissolution apparatus type 2 (paddle) with a dissolution medium of 900ml of 0.1M hydrochloride acid
at 50rpm (37±0.5 °C).
• 5ml of sample was withdrawn at predetermined time intervals replacing with an equal quantity of drug
free dissolution fluid. Time of withdrawal is 5,10,15,20,25,30 minutes.
• The samples withdrawn were filtered through 0.45μm membrane filter, and the drug content in each
sample was analyzed after suitable dilution by US ̸ VIS spectrophotometer at 266 nm, and cumulative
percent drug release was calculated using anequation obtained from a standard curve.
Formulation development of Fast dissolving tablets (FDTs)
Method for preparation of FDTs:
Mannitol (diluent) is mixed with the Superdisintegrant MCC and Kyron T-134 is passed through sieve no.
#60. They all mixed together in polyethene zip bag for 10 minutes. Then, kept it aside.
Aspartame the Sweetening agent is passed through #80 screen sieve. Mixed with above blend for 10
minutes and kept it aside.
PEG, Mg. stearate Binder and lubricants should be passed through #60 screen. Mix this with above blend
for 5 min. keep it aside. Compress tablet.
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• Method for preparation of FDTs:
• Mannitol (diluent) is mixed with the Superdisintegrant MCC and Kyron T-134
is passed through sieve no. #60. They all mixed together in polyethene zip bag
for 10 minutes. Then, kept it aside.
• Aspartame the Sweetening agent is passed through #80 screen sieve. Mixed
with above blend for 10 minutes and kept it aside.
• PEG, Mg. stearate Binder and lubricants should be passed through #60 screen.
Mix this with above blend for 5 min. keep it aside. Compress tablet.
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• Direct compression method [78]
Add Mannitol (Diluent) & other Superdisintegrents
Passed through #60 screen.All mixed together in polyethene
Zig bag for 10 min
Set aside
Add Aspartame (Sweetening agent)
Passed through #80 screen
Mix with above blend for 10 min and set aside
PEG 6000 , Mg.Stearate
Passed through #60 screen
Mix lubricant with above blend for 5min and keep aside
Compress Tablet
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Preparation of FDTs of Sertraline Hydrochloride:
• Tablets were prepared using tablet punching machine (Rimek, RSB-4 Mini
Press) to produce flat faced tablets weighing 200 mg each with a diameter of 4
mm.
• A minimum of 60 tablets were prepared for each batch. Before compression
tablet blends were evaluated for mass-volume relationship (bulk density,
tapped density,
• Hausner’s ratio, car’s index) and flow properties (Angle of repose). The
superdisintegrants (Microcrystalline Cellulose, Starch, Kyron T-134 and
Crosspovidone) in varying concentration (6-10% w/w) were used to develop
the tablets. All the ingredients were shown in Table 3.1.
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Ingredients Category T1 T2 T3
Sertraline HCl API 28.0 28.0 28.0
Microcrystalline
Superdisintegrants 10.0 10.0 10.0
Cellulose
Starch Superdisintegrants 10.0 – –
Kyron T-134 Superdisintegrants – 6.0 –
Crosspovidone Superdisintegrants – – 6.0
Mg. stearate Lubricant 4.0 4.0 4.0
Aspartame Sweetening Agent 8.0 8.0 8.0
Talc Glidant 8.0 8.0 8.0
PEG-6000 Binder 4.0 4.0 4.0
Mannitol Diluent 128 132 132
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Evaluation of blend:
Bulk density:79
• Apparent bulk density (ρb) was determined by pouring the blend into
graduated cylinder. A known amount of powder sample(M) was placed
in 100ml graduate cylinder and the volume (Vb) occupied by the powder
was recorded. The bulk density calculated using following formula:
𝐌
• ρb =
𝐕𝐛
Tapped density:79
• Take 50 ml powder blend in cylinder and tapped it for 100 times and
measure the difference.
• Tap density is calculated with given formula:
𝐌𝐚𝐬𝐬 𝐃𝐞𝐧𝐬𝐢𝐭𝐲
• Tapped density d =
𝐓𝐚𝐩𝐩𝐞𝐝 𝐃𝐞𝐧𝐬𝐢𝐭𝐲
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Angle of repose:79
• The funnel with an internal diameter opening of 1 cm was kept at a fixed
height of 2cm.
• The weighed powder was poured and retained in funnel and then allow
to flow through the funnel, the diameter of the powder heap formed was
measured by using a cm ruler at two location and repeated three times.
The mean angle of repose is then calculated by using by following
formula;
𝒉
𝜽 = 𝒕𝒂𝒏-1 ( )
𝒓
• Where,𝜃 = angle of repose
h= height(cm)
r = radius(cm)
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Hausner’s Ratio(H):79
• This is an indirect index of ease of powder flow. It is calculated by
following formula;
𝝆𝒕
H =
𝝆𝒃
𝜌𝑡 = tapped density
𝜌𝑏= Bulk density
Lower hausner ratio indicates better flow property
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Carr’s index:79
• It indicates powder flow properties it is expressed in percentage and it is given by
given formula;
Evaluation of Fast Dissolving Tablets
• Prepared fast dissolving tablets (FDTs) were evaluated for the following
parameters.
Weight variation test:81
• 20 tablets were weighed individually and average weight was determined. The %
deviation was calculated and checked for weight variation. Not more than two of
the individual weight deviated from the average weight by more than the
percentage shown in the table.
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Average weight of tablet(mg) (%) Deviation
80 mg or less ±10
More than 80mg but less than ±7.5
250mg
250mg or more ±5
Thickness:
• The thickness of prepared tablets was measured using Vernier caliper. Five tablets
from each batch were used for this test. The mean and standard deviation of each
batch were calculated.
Hardness:
• The tablet hardness (tablet crushing strength) is defined as the force required for
breaking a tablet in a diameter compression test. Tablets required a certain amount
of hardness or strength to withstand mechanical shocks of manufacturing
packaging and shipping. Hardness of 5 tablets from each batch was measured
using Monsanto hardness tester.
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Wetting time:81
• The wetting time of the tablets was measured using simple procedure. 5 circular
tissue papers of 10cm diameter were placed in petri dish. 10ml of water is added in
it. Tablet is placed on it and time to wet the tablet is observed simultaneously.
Disintegration time:82
• The disintegration time was measured using modified disintegration method. For
this purpose, a Petridish (10cm diameter) was filled with 10ml distilled water . the
tablet was carefully put in the Centre of the Petridish and the time for the tablet to
disintegrate completely into fine particles was noted as disintegration time.
Disintegration time of the five tablets from each batch was measured.
Drug content: 82,83
• The tablet equivalent to 50 mg of the drug was weighed accurately and triturated,
dissolve in 0.1M HCL and diluted to 100ml with 0.1M HCL. Absorbance was
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Level
Sr No Variables
Low Med High
Independent variables
1 Concentration of Kyron T-134 (mg) 3 6 9
2 Concentration of MCC (mg) 5 10 15
Coded value -1 0 1
Dependent variables
1 Disintegration time –
2 Wetting time –
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Optimization of Batch Formulae for Fast Dissolving Tablets (FDTs)
Preparation of Central Composite design batches
• To know the actual amount of 2 Superdisintegrent for the desirable property of fast
dissolving tablets a face centered central composite experimental design was
employed to optimize fast dissolving tablet formulation. In this design 2 factors are
evaluated, each at 3 levels response surface design and experimental trials are
performed at all 10 possible combinations. (8 non center point and 2 center point).
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Preparation of fast dissolving tablets:
• Tablets were prepared using tablet punching Variable levels in
machine (Rimek, RSB-4 Mini Press) to Batch Code coded form
produce flat faced tablets weighing 200 mg
X1 X2
each with a diameter of 4 mm. A minimum
F1 -1 0
of 60 tablets were prepared for each batch.
Before compression tablet blends were F2 0 0
evaluated for mass-volume relationship F3 0 1
(bulk density, tapped density, Hausner’s F4 1 -1
ratio, car’s index) and flow properties F5 -1 -1
(Angle of repose). The blends ready for F6 1 0
compression were converted into tablets F7 1 1
using a tablet punching machine as per F8 0 -1
given procedure. The composition of the F9 -1 1
Central composite design batches is shown F10 0 0
in Table respectively.
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F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Ingredients
(mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg)
Sertraline
HCL 28 28 28 28 28 28 28 28 28 28
Kyron T134 3 6 6 9 3 9 9 6 3 6
MCC 10 10 15 5 5 10 15 5 15 10
Mg stearate 4 4 4 4 4 4 4 4 4 4
Aspartame 8 8 8 8 8 8 8 8 8 8
Talc 8 8 8 8 8 8 8 8 8 8
PEG -6000 4 4 4 4 4 4 4 4 4 4
Mannitol 122 116 106 120 132 110 100 126 112 116
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❖ In vitro dissolution study:
• The release rate of sertraline hydrochloride from fast dissolving tablet was
determined using USP dissolution apparatus type 2 (Paddle) with a dissolution
medium of 900mL of 0.1M hydrochloride acid at 50 rpm (37 ± 0.5°C).
• 5 mL of sample was withdrawn at predetermined time intervals replacing with
an equal quantity of drug free dissolution fluid.
• Time of withdrawal is 5,10,15,20,25,30 minutes. The samples withdrawn were
filtered through 0.45µm membrane filter, and the drug content in each sample
was analyzed after suitable dilution by UV/ VIS spectrophotometer at 266 nm,
and cumulative percent drug release was calculated using an equation obtained
from a standard curve.
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❖ Result and discussion:
1. Identification of Sertraline HCl by Melting point determination:
• Melting point of Sertraline HCl was found in the range of 243-249 °C which is in accordance
with standard value.
2. Calibration curve:
Data of standard curve of sertraline in 0.1 M HCL; n=3, ±SD
Concentration(μg/ml) Absorption
10 0.038 ± 0.003
20 0.077 ± 0.005
30 0.123 ± 0.003
40 0.169 ± 0.004
50 0.213 ± 0.004
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3) Evaluation of Powder Blend:
Formulation with different Superdisintegrent:
• Results of bulk density, tapped density, Angle of repose, Carr’s index
Hausner’s ratio of trial batch
Trial Bulk Tapped Angle of Carr’s Hausner
no. density density repose index ratio
T1 0.50±0.02 0.58±0.01 31.08±0.01 17.00 1.30
T2 0. 43±0.01 0.50±0.02 28.09±0.02 20.42 1.20
T3 0.47±0.02 0.53±0.01 16.67 1.24
30.07±0.01
• Among all the three trials, trial 2 (MCC & Kyron) provide the best result
in flow property. Hence, combination of Kyron & MCC Superdisintegrent
is selected for manufacturing further batches of fast dissolving tablet.
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❖ Results of bulk density, tapped density, Angle of repose, Carr’s
index, Hausner’s ratio:
Batch Tapped Angle of Hausner
Bulk density Carr’s index
Code density repose ratio
F1 0.41±0.02 0.55±0.03 31.08±0.03 21.00 1.30
F2 0.46±0.03 0.58±0.04 29.09±0.03 16.89 1.25
F3 0.45±0.03 0.53±0.02 26.11±0.03 17.94 1.15
F4 0.41±0.02 0.54±0.02 30.86±0.03 16.67 1.26
F5 0.46±0.02 0.55±0.04 27.11±0.02 17.27 1.13
F6 0.46±0.04 0.57±0.02 26.11±0.02 19.77 1.24
F7 0.42±0.02 0.51±0.02 28.8±0.02 21.42 1.20
F8 0.46±0.02 0.56±0.02 26.61±0.03 17.30 1.21
F9 0.47±0.03 0.53±0.03 28.47±0.02 16.69 1.21
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4) Evaluation Of Fast Dissolving Tablets (FDTs):
• Results of thickness, width, hardness, %friability, Weight
variation of trial batch
Trial no. Wetting Disintegration Hardness % Friability
Time(sec) Time(sec)
T1 38±2.0 12±1.0 1.8±0.01 0.91
T2 28±1.0 7.5±1.0 2.5±0.01 0.60
T3 42±1.0 10±2.0 1.5±0.02 0.15
• Among all the three batch, Trial 2 with Kyron & MCC
Superdisintegrent gave the best possible results in disintegration
time, wetting time, hardness & friability so trial 2 was selected
for making further batches of fast dissolving tablets.
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▪ Results of thickness, width, hardness, %friability, Weight variation
▪ n =3 , ±SD
Batc
Thickness Width Hardness Weight
h %Friability
(mm) (mm) (Kg/sq. cm) variation
Code
F1 3.88±0.055 8.05±0.02 2.22±0.19 0.70 201±5
F2 3.82±0.025 8.04±0.01 2.00±0.05 0.60 198±6
F3 3.71±0.019 8.05±0.02 2.10±0.10 0.91 203±7
F4 3.96±0.011 8.14±0.22 2.12±0.07 0.90 201±6
F5 3.74±0.030 8.02±0.01 2.10±0.25 0.91 202±6
F6 3.77±0.030 8.04±0.03 2.00±0.05 0.92 201±5
F7 3.84±0.030 8.06±0.01 2.32±0.24 0.59 202±5
F8 4.21±0.017 8.05±0.02 2.00±0.36 0.61 201±6
F9 4.04±0.011 8.00±0.02 www.DuloM2ix..c1om1±0.13 0.15 199±6 58
▪ Results of wetting time & Disintegration time
▪ n =3, ±SD
Wetting Time (sec) Disintegration time (sec)
36±1.5 15±2.0
38±2.0 17±3.0
23±2.0 9±2.0
37±3.0 16±1.0
40±2.5 26±1.1
30±2.6 11±1.7
29±1.0 7±2.0
35±3.5 18±2.0
24±2.0 10±2.0
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5. Interpretation:
❑Response 1: Disintegration time (DT)
• Coded Eq: Disintegration Time= 13.4 – 3.33A – 6.17B + 2AB
• The Model F-Value of 53.75 implies the model is significant. There is only a
0.01% Chance that an F-Value this large could occur due to noise. The
predicted R2 of 0.8887 is in reasonable agreement with the adjusted R2 of
0.9462; the difference is less than 0.2. P Values less than 0.0500 indicate model
terms are significant. In this case A, B, AB are significant model terms.
❑Contour Plot:
• Contour plot helps us to understand the impact of independent variable over
the response DT (sec). From polynomial eq. and contour plot shows there is
decrease in the response as we increase the value of both A and B Factors are
the same time there is significant interaction observed between two factors i.e.
AB Interaction.
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.
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.
▪ We can also demonstrate same finding using the 3D Plot, as shown below.
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.
▪ Response 2: Wetting Time
▪ Coded Eq: Wetting Time: 33.2 – 6.67B
• The Model F-Value of 35.01 implies the model is significant. There is
only a 0.04% chance that and F-Value this large could occur due to noise.
The predicted R2 of 0.7338 is in reasonable agreement with the Adjusted
R2 of 0.7908; i.e. the difference is less than 0.2. P-values less than 0.0500
indicate model terms are significant. In this case B is significant model
term. Values greater than 0.1000 indicate the model terms are not
significant.
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.
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.
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.
• From polynomial Eq. Contour plot and 3D Plot, we observed that only Factor B have
an impact on the wetting time. With Increase in the factor B there was decrease in the
response (Negative relationship).
• Factor is having no impact on the response within the study range. No Interaction was
observed.
6) Comparison of marketed & F1 batch tablet:
▪ Information about marketed tablet of Sertraline HCL:
• Name of Drug: Sertraline Hydrochloride I.P. 25
• Batch No.1283
• Expiry Date: Jan.2025
• Manufactured By: Reliance Formulation Pvt. Ltd.
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▪ Comparison of % cumulative drug release between
marketed formulation & F7 batch
n=2, ±SD
Minutes F7 Batch Marketed tablet
0 0 0
5 72.50 ± 5.25 27.92 ± 1.05
10 80.70 ±2.66 37.73 ± 1.06
15 87.09 ± 1.62 40.91 ± 2.11
20 90.17 ± 1.00 44.85 ± 4.23
25 94.75 ± 2.67 47.33 ± 4.25
30 99.73 ± 1.64 54.65 ± 3.75
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.
• Cummulative % drug release
120.000
100.000
80.000
60.000
40.000
20.000
0.000
0 5 10 15 20 25 30 35
Time (min)
F7 MKT
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Cumulative % drug release
❖ Comparison of Wetting time, hardness &
disintegration time between marketed & F7 batch:
Evaluation Test Marketed tablet F7 batch
Disintegration time (sec) 11.0 6.0
Wetting time (sec) 27.0 25.0
Hardness (Kg/sq. cm) 2.1 2.5
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❖ Summary & conclusion:
• ISertraline hcl is antidepressants drug from bcs class 2 . To increase its
performance we used combination of 2 superdisintegrant machines & kyron.
Because of this it provides better disintegretion time.
• In present study demonstrated that out of 9 formulation containing MCC &
Kyron T 134 (15 & 9 respectively; F1 batch) were found to possess all
characteristics necessary for fast disintegrating tablet with better dissolution &
disintegration profile as compare to marketed one.
• In conclusion, overall results suggest that a 24% disintegrant concentration is
suitable for the preparation of fast disintegrating tablet of sertraline HCL using
MCC (Avicel pH 102) and Kyron T-134 seems to be the best.
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