RESEARCH ARTICLE
FORMULTAION AND EVALUATION OF FAST DISSOLVIG TABLET OF
ATENOLOL USING SUPERDISINTEGRANT-CROSSPOVIDONE AND
SWEETENING AGENT -SUCRALOSE.
MIZNA NIGARISH*, VANDANA ARORA SETHI
LLOYD INSTITUTE OF MANAGEMENT AND TECHNOLOGY
KNOWLEDGE
PARK-2,GREATER NOIDA-201306
(U.P)
PLOT
NO.2
ABSTRACT
the present study has been undertaken to prepare fast dissolving tablets of atenolol by direct
compression method with a view to enhance patient compliance. The super disintegrant used in this
study was crosspovidone and sucralose as a sweetening agent. A new formulation of atenolol tablet
was designed and compressed by direct compression method. Then its physical parameters
including hardness, friability, diameter, thickness, disintegration time, dissolution test were
performed for evaluation and characterization of this new formulation.It was observed in the result
that the tablet formulation F-4 was found to have maximum drug release at the end of 6 minutes
and considered as the most effective formulation.It was also concluded that direct compression
technique is a useful method for preparing fast dissolving tablets.
keywords: atenolol,fast dissolving tablets,superdisintegrant,sweetening agent,direct compression.
INTRODUCTION
The oral route is the most frequently used route for drug administration. Oral dosage forms are
intended for systemic effects resulting from drug absorption through gastro intestinal tract1.
The most common solid dosage forms in contemporary practice are tablets, which may be defined
as “Unit forms of solid medicaments prepared by compaction”. Most consists of a mixture of
powders which has been compacted in a die to produce a single rigid body2.
There are several reasons for the popularity of this group of dosage form
1.They employ the oral route of drug administration, which is generally the most acceptable route.
2.They permit a high degree of accuracy.
3.The dose of the active drug is contained in a relatively.small volume. Thus a concentrated dosage
form is produced, leading to the ease of packaging, transport, storage and administration3.
The tablet is the most widely used dosage form because of its convenience in terms of selfadministration, compactness, and ease in manufacturing. However, geriatric and paediatric patients
experience difficulty in swallowing conventional tablets, which leads to poor patient compliance.
To overcome this weakness, scientists have developed innovative drug delivery systems known as
fast dissoloving tablets (FDTs).
Atenolol, a beta-blocker used in the treatment of hypertension and angina pectoris. It is
incompletely absorbed from the gastrointestinal tract3 and has an oral Bioavailability of only 50%,
while the remaining is excreted unchanged in feaces. This is because of its poor absorption in lower
gastrointestinal tract. It undergoes hepatic first pass metabolism and its elimination half-life is 6 to 7
hours4. Atenolol results in poor Bioavailability when administered in the form of conventional
tablets because of hepatic first pass metabolism and exhibit fluctuation in the plasma drug level
resulting in reduction in drug concentration at receptor site. In the present study, an attempt was
made to develop fast dissolving tablets of atenolol and to improve bioavailability.An attempt was
made in the present investigation to prepare FDTs of atenolol using superdisintegrants and
sweetening agent for better patient compliance, rapid onset of action, increased bioavailability, and
good stability make these tablets popular as a dosage form of choice in the current market5,6.
MATERIALS AND METHODS
Materials Atenolol obtained as a gift from (Laxman chemicals,delhi, India). Microcrystaline
cellulose,Crosspovidone, Magnesium stearate, Talc,mannitol and sucralose from SD Fine chemicals
(new delhi, India). All other materials used were of pharmaceutical grade.
METHOD PREPARATION OF FAST DISSOLVING TABLET OF ATENOLOL
All the materials were passed through sieve no. 60. Required quantity of each ingredient was taken
for each specified formulation (Mentioned in Table no.1) and all the ingredients were subjected to
grinding to a required degree of fineness (except magnesium stearate and talc). The powdered blend
was evaluated for flow properties as follows and results were reported in Table no.2
EVALUATION OF ATENOLOL FAST DISSOLVING TABLET
Angle of repose :7
Angle of repose was determined using fixed funnel method. The blend was poured through a funnel
that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r)
was measured and the angle of repose (ө) was calculated using the formula,
θ=tan-1 (h/r)
Bulk density7,8
Bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume (Vb)
and weight of the blend (M) was determined. The bulk density was calculated by using the below
mentioned formula,
Bulk density =Weight of the blend
------------------------Volume of blend(Vb)
Tapped density: 7,9
The measuring cylinder containing a known mass of blend was tapped for a fixed number of times.
The minimum volume (Vt) occupied in the cylinder and the weight (M) of the blend was measured.
The tapped density was calculated using the following formula,
Tapped density= Weight of the blend
--------------------------------Volume occupied in the cylinder (Vt)
Total Porosity :9
It was determined by measuring the volume occupied by a selected weight of blend and the true
volume of blend. (The space occupied by the granules exclusive of spaces greater than the
intermolecular spaces)
Compressibility index :10
The simplest way for measurement of free flow of powder is compressibility , a indication of the
ease with which a material can be induced to flow is given by compressibility index (I) which is
calculated as follows,
Vb – Vt
I = ----------------Vb
Here, Vb is bulk volume and Vt is tapped volume. The value between 13-19% indicates a powder
with usually good flow characteristics, whereas above 21% indicate poor flowability.
Hausner’s Ratio :10
Hausner’s ratio is an indirect index of ease of powder flow. It is calculated by the following
formula,
Tapped density
Hausner’s ratio = -------------------Bulk density
Lower Hausner’s ratio (<1.25) indicates better flow properties and higher Hausner’s ratio (>1.25)
indicates poor flow properties.
COMPRESSION OF TABLETS BY USING DIRECT COMPRESSION METHOD :
Finally magnesium stearate and talc were added to the prepared blend. The mixed blend of drug and
excipients was compressed into tablets weighing 200mg using a flat faced punches of 8 mm
diameter in a rotary tablet press,weighing 200mg each with a diameter of 8 mm. A minimum of 50
tablets were prepared for each batch.
Weight variation test:11
Weight variation test was done by weighing 20 tablets individually, by using Sartorious balance.
Calculating the average weight and comparing the individual tablet weight to the average weight.
Tablet thickness11:
The thickness was measured by placing tablet between two arms of the Varnier calipers. 5 tablets
were taken and their thickness was measured.
Tablet hardness11:
The tablet hardness, which is the force required to break a tablet in a diametric compression force.
The hardness tester used in the study was Monsanto hardness tester, which applies force to the
tablet diametrically with the help of an inbuilt spring.3 tablets were choosen randomly and tested
for hardness.The average hardness of 3 determinations was recorded.
Tablet friability11:
The friability of the tablets was measured in a Roche friabilator (Lloyd institute of management and
technology,U.P,India). Tablets of a known weight (W0) or a sample of 20 tablets are dedusted in a
drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated
from the loss in weight as given in equation as below. The weight loss should not be more than 1 %.
Determination was made in triplicate
W0-W
% Friability = --------------- × 100
W0
Wetting time12:
The wetting time of the tablets can be measured using a simple procedure. Five circular tissue
papers of 10 cm diameter are placed in a petridish with a 10 cm diameter. Ten millimeters of watercontaining Eosin, a water- soluble dye, is added to petridish. A tablet is carefully placed on the
surface of the tissue paper. The time required for water to reach upper surface of the tablet is noted
as a wetting time.
disintegration test11:
The test was carried out on 6 tablets using Tablet disintegration tester (Lloyd institute of
management and technology,U.P, India) distilled water at 37oC ± 2oC was used as a disintegration
media and the time in second taken for complete disintegration of the tablet with no palable mass
remaining in the apparatus was measured in seconds.
In-vitro
In-vitro dissolution study13 :
The release rate of atenolol from mouth dissolving tablets was determined using United State
Pharmacopoeia (USP) XXIV dissolution testing apparatus II (paddle method). The dissolution test
was performed using 900 ml of phosphate buffer pH 6.8 as a dissolution medium, at 37±0.50C and
50 rpm. A sample (10 ml) of the solution was withdrawn from the dissolution apparatus at 5, 10, 15,
20, 25, 30, 35 and 40 min. The samples were filtered through a 0.45 UV/VIS spectrophotometer.
Cumulative percentage of drug release was calculated using an equation obtained from a standard
curve.
Table-1:Composition Of Fast Dissolving Tablets Of Atenolol
Table-2: Evaluation Of The Powder Blend
Figure 1: cumulative drug release vs time in minutes of prepared batches of F-1, F-2, F-3 and
F-4 of fast dissolving tablets of atenolol
RESULT AND DISCUSSION
Four formulations of Atenolol were prepared with combination of superdisintegrants like
crosspovidone and sweetening agent as sucralose. For each formulation, blend of drug and
excipients were prepared and evaluated for various parameters as explained earlier. The formulated
blends were evaluated and the results are shown in the table 2. The angle of repose was in the range
of 26.55±0.329 to 28.85±0.175 indicating good flow property. The bulk density and tapped density
was in the range of 0.4168±0.006 to 0.4982±0.009 gm/ml and 0.4225±0.016to 0.4944±0.018gm/ml.
The compressibility index and Hauser’s ratio was in the range of 12.26± 1.82 to 15.14 ±1.93% and
1.1538±0.032 to 1.1802±0.033 indicating good flow property. The powder blend was compressed
using direct compression technique. The compressed tablets were evaluated for physical properties
and the results are tabulated in table 3. The hardness was in the range of 3.4 to 3.7 kg/cm2.
Uniformity of weight was found to be in the range of 200.6 ± 1.12 to 202.85±1.44 mg. The
friability of all the formulation was within 1%, and was in the range of 0.38 to 0.62 % indicating a
good mechanical resistance of tablets. The wetting time for all the formulated tablets was in the
range of 12 ± 1.10 to 119 ± 1.39 sec. The disintegration time of all the formulated tablets was found
to be in the range of 12 ± 1.49 to 47 ± 1.31 sec. All the formulations in in-vitro drug release results
were mentioned in the Table no.4. The results revealed that the increase in proportion of
superdisintegrant was associated with change in the overall cumulative drug release rate. Release
profile of F-4 was found to have maximum release of 94.65 % at the end of 6 minutes. The drug
release from all batches was found to be concentration dependent.
CONCLUSION
In the present work efforts have been made to prepare and evaluate fast dissolving tablets of
atenolol with combination of superdisintegrant like crospovidone and sweetening agent as sucralose
by direct compression technique. The results revealed that the increased proportion of
superdisintegrant crosspovidone were associated with change in the overall cumulative drug release
rate. Release profile of F-4 was found to have maximum release of 94.65 % at the end of 6 minutes.
The drug release from all batches was found to be concentration dependent. The fast dissolving
tablets (FDT) found to have excellent physical characters. The superdisintegrant and sweetening
agent were also found to be compatible with the other excipients of the formulation as well as with
drug, which is evident from the drug release. Hence the formulation of F-4 fulfills the objective of
the present study.
ACKNOWLEDGEMENT
The author is thankful to Prof. Vandana Arora Sethi, H.O.D, LLOYD INSTITUTE OF
MANAGEMENT AND TECHNOLOGY for providing all the necessary facilities and laxman
chemicals for giving free gift sample of drug.
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