Asian J. Research Chem. 2(2): July-Sept.

, 2009

ISSN 0974-4169 www.ajrconline.org

RESEARCH ARTICLE

Effect of Surfactants on the Crystal Properties and Dissolution Behavior of

Aspirin
MA Ahmed1, AM Rhgigh2 and F Shakeel*3
1
Department of Pharmaceutical chemistry, Faculty of Pharmacy, Al-Arab Medical University, Benghazi, Libya
2
Department of Pharmaceutics, Faculty of Pharmacy, Alfateh University, Tripoli, Libya
3
Department of Pharmaceutics, Faculty of Pharmacy, Al-Arab Medical University, Benghazi, Libya
*Corresponding Author E-mail: faiyazs@fastmail.fm

ABSTRACT
The aim of present investigation was to evaluate the effects of different surfactants on crystal properties and
dissolution behavior of aspirin. Aspirin was crystallized through methanol in the presence of three surfactants namely
cetrimide (cationic), sodium lauryl sulphate (anionic) and Tween 80 (non-ionic). All the three surfactants were used in
various concentrations ranging from 0.0001M to 0.1M. The crystals were characterized for habit, melting points, bulk
density, true density, solubility and drug-surfactant interaction studies using infra-red spectroscopy. Dissolution profile
of aspirin tablets prepared with surfactant was compared with control aspirin tablets using USP dissolution apparatus.
The concentration and charge of the surfactants have brought about modifications in the crystal habit of aspirin, which
has subsequently affected the crystal properties such as density and equilibrium solubility. IR spectroscopic studies
revealed that the internal lattice structure of aspirin was not altered in presence of the surfactants in all of the employed
concentrations. However, presence of surfactants considerably modified crystal habit and other crystal properties.
Such changes apparently appeared to be responsible for altered equilibrium solubility. Presence of surfactant (0.1 M
SLS) in aspirin tablets enhanced the dissolution of aspirin significantly as compared to control aspirin tablets (P<0.05).
From these results it can be concluded that the choice of selection of surfactants and optimization of its concentration
is important in manufacturing of dosage forms with aspirin.

KEY WORDS: Crystal habit, crystallization techniques, surfactants and aspirin.

INTRODUCTION:
Pharmaceutical drugs exist in different crystal forms 1. A
crystalline solid is characterized by a definite external
and internal structure. Habit describes the external
structure and polymorphic state refers to the internal
structure of a crystal 2. Polymorphism, which is the
definite arrangement of molecules within a solid, has
been known to influence various physicochemical and
biological properties of a crystalline moiety 3. However,
crystal habit has been paid scant attention 2.
Crystallization is commonly employed as the final step
for purification of a drug 4. Use of different solvents and
processing conditions may alter the polymorphic state
and/or habit of the purified drug, leading to variation in
raw material characteristics 4. In addition, crystal habit
influences flowability, packing, compaction,
syringability, stability and dissolution characteristics of a
drug powder 5.
Therefore, it becomes necessary to identify the factors
which alter the crystal habit of a drug and to assess the
modifications of the properties of the drug altered by
them.
The use of adjuvants in pharmaceutical formulations have
shown to affect the crystalline properties of drug materials
and consequently altered the pharmaceutical performance
criteria such as dissolution, equilibrium solubility,
compressibility and stability 5. The capacity of surfactants
in solubilizing the drugs depends on numerous factors
such as chemical structure of the surfactant, chemical
structure of the drug, temperature, pH and ionic strength 6.
Although surfactants have a wide usage in development
of dosage forms, earlier studies have shown their effects
on crystalline properties of drugs and subsequently the
pharmaceutical performance of the drug 6. The present
study was carried out to investigate the effect of surfactant
on the crystalline properties of aspirin.

Aspirin or acetylsalicylic acid is a salicylate drug often

Received on 01.12.2008 Modified on 12.02.2009 used as an analgesic, antipyretic and as an anti-
Accepted on 25.04.2009 © AJRC All right reserved inflammatory drug 7. It also has an antiplatelet effect and
Asian J. Research Chem. 2(2): April.-June, 2009 page 202-206 is used in long term, low doses to prevent heart attacks
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 Asian J. Research Chem. 2(2): July-Sept., 2009
Table I: Effect of various molar concentrations of Tween 80 on the properties of aspirin crystals from methanol
Parameters Pure aspirin Crystals obtained using Tween-80
0.1M 0.01M 0.001M 0.0001M
Melting point range ( 0C) 128-135 129-133 125-129 127-133 130-133
Solubility (µg/ml) 135.469 141.553 124.300 96.407 95.436
Bulk density (gm/cm3 ) 1.302 1.084 1.168 1.213 1.206
True density (gm/cm3 ) 0.970 0.959 0.825 1.171 0.996
Porosity (%) 25.4 11.61 29.40 03.50 17.61

Table II: Effect of various molar concentrations of SLS on the properties of aspirin crystals from methanol
Parameters Pure aspirin Crystals obtained using SLS
0.1M 0.01M 0.001M 0.0001M
Melting point range ( 0C) 128-135 128-140 128-132 129-140 128-140
Solubility (µg/ml) 135.469 115.146 97.864 89.223 162.136
Bulk density (gm/cm3 ) 1.302 1.105 1.219 1.083 1.057
True density (gm/cm3 ) 0.970 0.928 0.219 0.895 0.982
Porosity (%) 25.4 16.00 81.98 17.4 7.3

Table III: Effect of various molar concentrations of cetrimide on the properties of aspirin crystals from methanol
Parameters Pure aspirin Crystals obtained using the cetrimide
0.1M 0.01M 0.001M 0.0001M
Melting point range ( 0C) 128-135 125-130 120-128 127-133 126.8-131.8
Solubility (µg/ml) 135.469 282.331 141.068 120.631 122.475
Bulk density (gm/cm3 ) 1.302 1.160 1.322 1.171 1.075
True density (gm/cm3 ) 0.970 0.230 0.301 0.197 1.030
Porosity (%) 25.4 80.13 77.22 83.20 4.3

and blood clot formation in people at high risk for aspirin dissolved. The supersaturated solution was
developing blood clots 7. Aspirin is known to exist in filtered and to this solution 5 ml of each of the surfactant
different crystalline forms. Earlier reports on the solutions with different molarities were added. The
polymorphism of aspirin have revealed that the solutions were kept undisturbed for one week at room
difference in the physicochemical properties of the drug temperature and the formed crystals were removed by
could be due to the differences in crystal size and habit filtration and stored in air tight containers.
or due to crystal defects 8.
Fig. 1 Crystals of aspirin prepared with (A) Standard aspirin,
In the present study, aspirin was crystallized through (B) Aspirin with Tween 80, (C) Aspirin with SLS and (D)
methanol in the presence of three surfactants namely Aspirin with cetrimide observed under light microscope
cetrimide (cationic), sodium lauryl sulphate [SLS]
(anionic) and Tween 80 (non-ionic) in various
concentrations ranging from 0.0001M to 0.1M. The
effect of surfactants in various concentrations in the
aspirin crystals were characterized by melting point, true
and bulk density, porosity, solubility studies and infra
red (IR) spectroscopic analysis.

MATERIALS AND METHODS:

Materials:
Aspirin crystals were obtained from Synopharm (A) (B)
Limited, Germany. Tween 80, Sodium lauryl sulphate
(SLS), cetrimide and methanol were purchased from
Atlas chemical Industries, USA. All other reagents used
were of analytical grade.

Preparation of crystals:
Surfactant solutions each of Tween 80, sodium lauryl
sulphate and cetrimide were prepared in methanol with
different molarities of 0.0001M, 0.001M, 0.01M and
0.1M. Excess quantities of aspirin powder were
dissolved in methanol using magnetic stirrer (M5
magnetic stirrer, Finemech, Germany) until no further (C) (D)

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 Asian J. Research Chem. 2(2): July-Sept., 2009
Characterization of crystals:
Crystal habit determination:
Carl Zeiss light microscopy (Axioskop 40 FL, Carl
Zeiss, Germany) fitted with canon power shot G3 digital
camera was used to study morphology and habit forms
of aspirin crystals. The microscopy was performed at
low magnification (40X and 100X) level.
Melting point:
The melting points of all the obtained crystals were
recorded by the conventional capillary tube method and
the experiment was repeated thrice for accuracy and the
mean value was recorded.
Fig. 2 IR spectra of control aspirin, aspirin with 0.1 M Tween
80 and aspirin with 0.0001 M Tween 80
True density and Bulk density:
Liquid displacement method using benzene was used to
determine the true density and bulk density of the
crystals. Crystalline material was crushed to obtain
60/80 mesh powder and this powder was used to obtain
the bulk density and the crystals. Crystals as such was
used to obtain bulk density. In both the cases, the weight
of liquid displaced by the presence of crystalline
compound was obtained experimentally. The weight of
the liquid when divided by its density, gave the volume,
which is in fact the volume of the crystalline material.
Since definite weight of crystals was used in the
experiment, the true density and bulk density of crystals
were obtained by dividing the weight of the crystals by
their volume.
Porosity:
Porosity was determined by using the value of true
density and bulk density of the crystals. It was
determined by using the formula:
= (1-true density/bulk density) X 100.
Where, is the porosity of aspirin crystals.
Fig. 3 IR spectra of control aspirin, aspirin with 0.1 M SLS
and aspirin with 0.0001 M SLS
Solubility:
The crystals were added in excess to 50 ml of distilled
water using magnetic stirrer (M5 magnetic stirrer,
Finemech, Germany). The saturated solution was filtered
using whatman filter paper and the concentration of the
drug in the saturated solution was determined by using
UV spectrophotometer (Hitachi Ltd., Tokyo, Japan) at
the wavelength of 265 nm 9.
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Infra red (IR) spectroscopy:
IR spectra of all the crystals were obtained using JASCO
IR spectrophotometer by the conventional KBr pellet
method. KBr pellets of the crystals were obtained by
pressing the crystals with potassium bromide and
subjected to IR studies.
Formulation of aspirin tablets:
Each tablet containing 300 mg of pure aspirin or aspirin
crystals prepared with different molar concentration of
SLS, 100 mg of anhydrous lactose, 10 mg of povidone,
5 mg of magnesium stearate, 5 mg of talc and 75 mg of
methyl cellulose (MC). The tablets were prepared by the
wet granulation method in a batch size of 60 tablets 9.
Pure aspirin or crystals prepared with SLS, lactose and
methyl cellulose were passed through a #12 mesh screen
and blended for 15 min.
Fig. 4 IR spectra of control aspirin, aspirin with 0.1 M
cetrimide and aspirin with 0.0001 M cetrimide
The blend was transferred to a glass mortar and
granulated with 6 ml of 6 % povidone in isopropyl
alcohol by gentle trituration. The granules were dried at
50 oC for 1 h and passed through a #30 mesh screen.
Magnesium stearate (lubricant) and talc (glidant) were
blended with granules for 2 min. This mixture was
compressed into tablets.
In vitro dissolution studies:
Dissolution studies were conducted into the USP
dissolution apparatus II in 900 ml of distilled water at
37±1 C. Dissolution apparatus was agitated at 50 rpm
with six tablets per study. Samples of 3 ml were
withdrawn at regular interval (0, 15, 30, 45, 60, 75, 90,
105 and 120 min) with media replacement, filtered
through 0.45 m filters and assayed
spectrophotometrically for drug content at the
wavelength of 265 nm 9.
RESULTS AND DISCUSSION:
Aspirin crystals were successfully prepared using
different surfactants. The photographs of pure aspirin
crystals and crystals prepared with surfactants are shown
in Figure 1. The size and habit of crystals was clearly
changed when aspirin crystals were prepared with
different surfactants (Figure 1). The surface of pure
aspirin crystals was rough as compared to crystals
prepared with different surfactants (Figure 1A). The
most smooth and fine aspirin crystals were obtained with
SLS (Figure 1C). The effect of surfactant concentration
on melting point, true density, bulk density, crystal
porosity and solubility of aspirin crystals are shown in
Table I-III. The melting points of all crystals and pure
aspirin powder were obtained by conventional capillary
tube method. Crystals obtained with solution containing
0.01M concentration of Tween 80 and 0.1M
concentration of cetrimide has shown a low melting
range when compared with pure aspirin (Table 1 and
III). Deviations in melting range were observed for SLS
crystals (Table II). Variations were observed in the true
density and bulk density of aspirin crystals prepared
with different concentration of SLS and Cetrimide
(Table II-III). Significant differences in porosity were
observed in crystals prepared with 0.0001M SLS,
0.0001M cetrimide and 0.001M Tween-80 (P<0.05).
Such changes indicated the modification of crystal habit
of the drug which may influence the hardness,
disintegration time and dissolution rate of the
formulations. Crystals obtained with 0.01M and 0.001M
SLS has shown very poor solubility (Table II), whereas
higher solubility was observed in crystals prepared with
0.1M Cetrimide (Table III). This clearly indicated that
the presence and concentration of surfactants has marked
effects on pure aspirin and these variations may
influence the dissolution rate as well as bioavailability of
aspirin when used together with such surfactants. IR
spectra of control aspirin crystals and crystals prepared
with different surfactants are shown in Figure 2-4. It was
found that basic IR peaks of control aspirin and crystals
prepared with different surfactants were nearly similar
(Figure 2-4). This indicated that there were no chemical
changes in the obtained aspirin crystals and subsequently
no interaction between the drug and the surfactants.
Different molar concentrations of SLS were selected for
the preparation of tablets. Dissolution profiles of control
aspirin tablets and tablets prepared with different molar
concentration of SLS were compared by applying one
way analysis of variance (ANOVA). The dissolution
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profiles of tablets prepared with different concentration
of SLS were significantly different from control aspirin
tablets (P<0.05). The best drug release (97 %) was
obtained in 120 min with 0.1 M concentration of SLS
(Figure 5). Overall SLS was found to be the best
surfactant for the preparation of aspirin tablets.
CONCLUSION:
This study revealed that not only the crystal habit is
influenced by the surfactants, but their densities and
consequently the porosities are also altered. Such
changes apparently appear to be responsible for altered
equilibrium solubilities. These modifications have an
effect on other parameters such as dissolution and
bioavailability of the formulations and thus it was
concluded that the choice of selection of surfactants and
optimization of its concentration is important in
manufacturing of dosage forms with aspirin.
Fig. 5 Comparative dissolution profile of control aspirin tablets
(mean ± SD, n=3) and tablets prepared with different molar
concentration of SLS
100
80
% Dissolution
60
40
20
0
0 30 60 90
Time (Min)
Control 0.001M 0.01M
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0.1M
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