Effect of Surfactants on the Crystal Properties and Dissolution Behavior of Aspirin

 

MA Ahmed1, AM Rhgigh2 and F Shakeel*3

1Department of Pharmaceutical chemistry, Faculty of Pharmacy, Al-Arab Medical University, Benghazi, Libya

2Department of Pharmaceutics, Faculty of Pharmacy, Alfateh University, Tripoli, Libya

3Department 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 used as an analgesic, antipyretic and as an anti-inflammatory drug 7. It also has an antiplatelet effect and is used in long term, low doses to prevent heart attacks


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 developing blood clots 7. Aspirin is known to exist in different crystalline forms. Earlier reports on the polymorphism of aspirin have revealed that the difference in the physicochemical properties of the drug could be due to the differences in crystal size and habit or due to crystal defects 8.  

 

In the present study, aspirin was crystallized through methanol in the presence of three surfactants namely 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 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

 

aspirin dissolved. The supersaturated solution was filtered and to this solution 5 ml of each of the surfactant solutions with different molarities were added. The solutions were kept undisturbed for one week at room temperature and the formed crystals were removed by filtration and stored in air tight containers.

 

Fig. 1 Crystals of aspirin prepared with (A) Standard aspirin, (B) Aspirin with Tween 80, (C) Aspirin with SLS and (D) Aspirin with cetrimide observed under light microscope

 

(A)                                         (B)

 

(C)                                        (D)

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.

 

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 μm 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

 

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

 

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Received on 01.12.2008        Modified on 12.02.2009

Accepted on 25.04.2009        © AJRC All right reserved

Asian J. Research Chem.  2(2): April.-June, 2009 page 202-206