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Formulation of Aspirin Tablets using fewer

excipients by Direct Compression.

Article January 2011

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Pakistan Journal of Pharmacology
Vol.28, No.1, July 2011, pp.31-37

FORMULATION OF ASPIRIN TABLETS

USING FEWER EXCIPIENTS BY DIRECT COMPRESSION
SAIMA ERUM, FOUZIA HASSAN, SYED MUHAMMAD FARID HASAN*
AND SABAHAT JABEEN
Department of Pharmaceutics, Faculty of Pharmacy,
University of Karachi, Karachi, Pakistan

ABSTRACT:
The objective of the present study was to formulate aspirin tablets by direct compression
method using fewer excipients and to compare this formulation with the other brands.
Design formulation besides aspirin contained excipients that comprises of lactose, corn
starch and aerosil. The blend was compressed on a single punch machine, tablets were
subjected to various tests (uniformity of weights, diameter and thickness, hardness,
disintegration, dissolution and assay of the drug) and the results were compared with
some of the available brands. The studied formulation showed close resemblance with the
available marketed brands and were also in compliance with the official specifications.
Using the present approach, further studies should be designed using other actives and
excipients to get a cost effective product.

Keywords: Aspirin, tablet formulation, direct compression.

INTRODUCTION technique. It is most widely used drug in the

Though, pharmaceutical research have
been focused on development of new and
more compliant dosage forms, tablets still
remain popular due to their stability, ease of
handling and convenience of dosing and
account for more than 80% of all dosage forms
administered (Jivraj et al., 2000). These are
manufactured by wet granulation, dry
granulation and direct compression (DC)
methods (Jones, 2008). DC is advantageous
over other methods of tablet manufacturing as
it requires fewer unit operations, consequently
low cost and less time consumption, generates
optimum possible bioavailability (Yasmeen et
al., 2005), low microbial level due to absence
of moisture (Ibrahim and Olurinola, 1991) and
produces faster dissolution rates for certain
compounds (Jivraj et al., 2000). This method
is preferred for tablet manufacturing especially
in case of thermolabile and moisture-sensitive
drugs (Jivraj et al., 2000). Aspirin is a
commercial example of a DC tablet
granulation prepared by the dry granulation
world (Michael Gossop, 2007) as an analgesic,
anti-inflammatory and antipyretic agent
(Sweetman, 2009), however, many workers
have investigated its clinical profiles in a
number of other medical conditions such as
cardiovascular (Buring, 2006, Moyad, 2001,
Berger et al., 2009), cancer (Moyad, 2001,
Chan et al., 2009, Cook et al., 2005) and
diabetes (Yang et al., 2009, Ong et al., 2010)
and have found promising results.
The objective of the present study was to
make a new formulation of aspirin tablets by
DC using a fewer excipients in three trail
batches and to compare this formulation with
the available brands in the local market
containing aspirin in the same strength.
MATERIALS AND METHODS
Reagents
Sodium hydroxide, hydrochloric acid,
acetonitrile, formic acid, glacial acetic acid,
sodium 1-heptane sulphonate, acetate buffer

Correspondence to: e-mail: faridsm2002@yahoo.com

32
and phenol red, all reagents were purchased
from Merck Germany.
Formulation Composition
A new formulation was designed
consisting of: Aspirin (donated by Reckitt
Benckiser, Pakistan Ltd.), lactose, starch and
aerosil (FMC Corporation, USA).
Composition of the formulation is given in
Table 1.
Commercial Brands
Different brands of aspirin 300mg were
purchased from the local market and were
assigned randomly as B1, B2, B3, B4 and B5.
Trail Batches
Active pharmaceutical ingredient (API)
and all the other excipients, as mentioned in
Table 1, were accurately weighed and were
passed through 20 mesh sieve in order to
remove foreign material and to get uniform
particle size. The powder was blended in a
poly bag by tumbling for five minutes. The
blend was transferred directly into the hopper
of single punch machine (Erweka, GmbH,
Germany) having caplet shaped concave
punch and was compressed manually. Three
trial batches (T1, T2 and T3) were prepared
using the same procedure on alternate days as
described above and each batch was tested on
day of compression in order to avoid any
change in hardness, moisture content and any
other physical parameter. All the batches were
compressed at room temperature.
Evaluation of Tablet Properties
All the trial batches of aspirin and the
commercial brands were evaluated using USP
Table 1
Composition of Aspirin 300mg tablets prepared by DC
S. No. Ingredients Mg/Tablet
1. Aspirin 300
2. Lactose 80
3. Corn starch 15
4. Aerosil 5 1.25
Total 400
Formulation of Aspirin Tablets
28/NF 23 (USP 28/NF 23, 2005) and by non-
pharmacopoeial tests.
Weight variation test
Weight variation test of each trail
formulation and commercial brands was
carried out by taking average weight of 20
individually weighed tablets on an analytical
balance (Sartorious GmbH type A 6801) and
compared with permissible limits.
Diameter and Thickness
Random samples of 10 tablets were
selected from each of the trial batches and
commercial brands and their diameter and
thickness was calculated in centimeters with
the help of micrometer screw gauge.
Hardness
Hardness of randomly selected 10 tablets
of each brand and trial formulation batch was
measured using Hardness Tester (Fujiwara,
Seisukusho Corporation, Japan). Load was
given to tablets in a diametric direction to
determine an actual load when the tablet was
broken.
Friability Testing
Friability test was preformed on twenty
randomly selected tablets of each brand and
trial formulation batches which were cleared
from any loose dust with help of soft brush
and weighed accurately for their initial weight.
Each set of tablets were placed separately in
Friability Tester (H. Jurgens and Co- GmbH,
D2800, Germany) and run for 4 minutes
(25rpm). After removing from tester, tablets
were cleared from any loose dust and their
final weight was determined to calculate loss
Percentage w/w g/1000 tablets
75 300
20 80
3.75 15
5
100 400
Erum et al.
of weight which is indicative of mechanical
strength to withstand this type of wear.
Disintegration Test
Disintegration time was measured by
putting 6 tablets of each of the studied
formulation separately in basket rack assembly
(Erweka ZT-2, Germany) using disks to avoid
floating of tablets in 900 ml distill water
maintained at 372C.
Dissolution Test
Dissolution of commercially available
brands and formulated aspirin tablets was
measured by paddle method in dissolution
apparatus (Erweka GmbH, Germany) using
0.05M acetate buffer solution 500 mL (pH 4.5)
at 50 rpm, maintained at 370.5C. After 30
minutes the absorbance of suitably diluted
portions in same medium was determined
against absorbance of standard preparation at
265nm using UV-VIS Spectrophotometer
(Shimadzu UV-150-02 Double beam
spectrophotometer).
Assay
Twenty tablets were accurately weighed
and than triturated in a mortar with pestle,
amount equivalent to 100 mg of aspirin was
transferred to a 50 mL volumetric flask,
diluted by 20 mL of diluting solution
(acetonitrile and formic acid 99:1). The
volumetric flask was shaken manually,
centrifuged at 3000 rpm for 5 minutes and than
the stock prepared was diluted. An aliquot of
the diluted solution was injected into a liquid
chromatograph with a detector set at 280 nm.
The responses were compared with the
standard to determine the quantity in mg of
aspirin present in the sample.
RESULTS AND DISCUSSION
Although aspirin formulation is
manufactured by dry method which involves
few steps as compare to wet granulation, yet
there is a wide variation among the cost of
various brands available in the local market.
Thus, the purpose of the present work was to
formulate aspirin formulation by DC using a
33
simplified formula that contains only few
ingredients and from the finding further work
will be planned by varying the composition
using optimization until a perfect formulation
of this drug is obtained. Various excipients are
available for DC method, we selected those
excipients that are used commonly. Since the
major part of the formulation is active
ingredient (75%), the remaining bulk is
adjusted by the excipients (25%). These
include lactose, corn starch and aerosol.
Microcrystalline cellulose/lactose in
formulations gives improved average potency
compared to microcrystalline cellulose/
dicalcium phosphate anhydrous (Morris et al.,
2009). Tablets containing lactose showed rapid
disintegration (Kamp et al., 1986). Starch,
commonly used as binder, offers various
advantages such as its abundance,
inexpensiveness, relative inertness and no
reaction with majority of active drug
substances that promote its use for
pharmaceuticals as directly compressible
material as indicated by many workers
(Haware et al., 2009, Elvira et al., 2002,
Korhonen et al., 2000, Sanghvi et al., 1993).
Incorporation of glidants in direct compression
formulations is aimed to improve powder flow
and control tablet weight. Due to their small
particle size and extremely low-density silica-
type glidants are most efficient among several
other groups (Sheth et al., 1980, Varthalis and
Pilpel 1977). Gazikolovi et al, presented
results of lithium carbonate tablets made by
DC concluding that lactose and corn starch
give best properties to tablets (Gazikolovi et
al., 1999). In another evaluation best
characteristics were observed in calcium
acetate tablets prepared by DC and wet
granulation method using maize starch
(Obrenovic et al., 2000).
All the trial batches (T1, T2 and T3) were
easily compressed on single punch machine
and the resulting tablets were evaluated using
pharmacopoeial and nonpharmacopeial tests.
The weight variation test is simplified and
alternative to content uniformity test to assure
therapeutic utility (Katori et al., 2001) and is
an indicator of variations in the drug content
34 Formulation of Aspirin Tablets

Table 2
Unofficial Tests

Formulation Diameter (cm) Thickness (cm) Hardness (Kg) Friability

Code X SD, n = 10 X SD, n =10 X SD, n = 10 (%), n=20
B1 1.140.0425 0.560.0438 2.170.4514 0.58
B2 1.590.0205 0.710.0922 4.841.0368 0.23
B3 1.560.0394 0.580.0410 6.261.8616 0.24
B4 1.160.0940 0.440.0690 4.410.7790 0.52
B5 1.610.0348 0.700.0343 6.941.4276 0.26
T1 1.330.0638 0.380.2541 4.741.2541 0.24
T2 1.340.0639 0.390.2499 4.671.1918 0.28
T3 1.340.0328 0.380.0850 4.901.7986 0.31

Table 3
Official Tests with permissible limits (USP 28/NF 23, 2005)

Weight (g) Average Average Assay

Formulation X SD, n = 20 Disintegration time Dissolution (%), n=20
Code (Sec.), n=6 n=6
5 % Within 30 minutes Not less than 80% 95-105%
B1 0.370.0056 13 85.09 97.28
B2 0.380.0103 15 78.07 96.74
B3 0.330.0061 10 89.08 98.88
B4 0.360.0082 10 99.08 100.11
B5 0.360.0057 15 81.01 97.21
T1 0.400.0215 20 100.65 99.07
T2 0.390.0261 15 95.00 97.01
T3 0.400.0125 20 91.00 96.05

(Rawlins, 1995). Since, various factors effect
uniformity of weight of single-unit dose
therefore, pharmacopoeias have established
standards and specifications that provide
permissible limits for weight variation. All the
trial batches complies weight variation test
according to specification given in the USP
pharmacopeia 2005 (USP 28/NF 23, 2005).
The weight of twenty tablets (X S.D) of the
trial batches and the commercial brands are
given in Table 3. A close resemblance in tablet
weight is evident from the Table 3. Following
Figure represents weight of tablets versus
number of tablets of one trial batch (T1) for
illustration. It appears that the compression
weight of B3 is lower as compare to other
commercial brands studied in the present work
but all these likewise our batches found to
fulfills the requirements of weight variation
test as stated by the US pharmacopoeia.
The diameter, thickness and hardness
(X SD) ranged from: 1.140.0425cm to
1.610.0348cm (B1 and B5), 0.440.0690cm
to 0.710.0922cm (B4 and B2),
2.170.4514Kg to 6.941.4276Kg (B1 and
B5) while friability ranged from 0.23% to
0.58% (B2 and B1), for commercial brands,
1.330.0638cm to 1.340.0639cm (T1 and
T2), 0.380.0850cm to 0.390.2499cm (T3
and T2), 4.671.1918Kg to 4.901.7986Kg
(T2 and T3) while friability ranged from
0.24% to 0.31% (T1 and T3) for trial batches,
respectively. Comparison of these values for
trail batches shows no difference in diameter,
hardness and friability as all these are within
Erum et al. 35

the range of the commercial brands. Only
thickness of the trial batches differs yet not far
from commercial brands (Table 2).
After physical test the tablets were
subjected to chemical tests that include assay,
disintegration and dissolution. Assay of the
tablet indicates amount of active in the
composite sample, our results of assay shows
that both the formulations under study meets
the official requirement of the assay (95% to
time to disintegrate i-e; 10 seconds, B1 took
13 seconds while B2 and B5 both took 15
seconds (Table 3). The trial batches T1 and T3
took similar (20 Sec.) but slightly higher time
to disintegrate as compare to T2 (15 Sec.). All
meets disintegration limits as set by USP (USP
28/NF 23, 2005). Fast disintegration is
required for analgesics in order to get a prompt
effect. Finally, when the dissolution test was
carried out for commercial brands, B2 showed
least dissolution rate i.e. 78%, thus failing

No. of Tabs. Weight (gm) (X? )

SD (X? )+ 1SD (X? )+2SD
(X? )+3SD (X? )-1SD (X? )-2SD
(X? )-3SD Upper Limit (+5%) Lower Limit (+5%)

0.46

0.44
Weight of Tablets (g)

0.42

0.4

0.38

0.36

0.34

0.32
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

No of tablets

Fig. Weight of tablets v/s No. of Aspirin Tablets (T1)

(X ) = 0.400 S.D =0.012 (X ) + 1S.D= 0.412 (X ) + 2SD = 0.424
(X ) + 3SD = 0.436 (X ) - 1SD = 0.388 (X ) - 2SD = 0.376 (X ) - 3SD = 0.364
Upper Limit (+5%)= 0.42 Lower Limit (-5%) = 0.38

105%) as shown in the Table 3. Disintegration pharmacopoeial requirements while highest

evaluates availability of a drug for dissolution
and absorption from the gastrointestinal tract
(Block, 2007). When disintegration data was
evaluated, the results revealed rapid
disintegration of some brands. In case of
Commercial brands, B3 and B4 took short
percentage release was obtained by B4 which
is 99%. The remaining brands give more than
80% release of the active within 30 minutes.
Dissolution of trial batches was found to be
better than most of commercial brands tested
(range: 91% to 101% for T3 and T1
36
respectively), this might be due to the use of
few excipients. Rapid disintegration of tablets
favors high dissolution rates.
CONCLUSION
In the present work, aspirin tablets using
fewer excipients were manufactured
successfully that fulfills all the
pharmacopoeial limits. This type of study may
also be done on other drugs to get a cost
effective product. Further work using
optimization technique is recommended for
future studies using present data as a reference
guide.
ACKNOWLEDGEMENTS
We are grateful to Yasir Faraz Abbasi,
Department of Pharmacy, Ziauddin Medical
University, Karachi, Pakistan for his co-
operation and useful suggestions.
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