Iraqi J Pharm Sci, Vol.30(1) 2021 Ebastine surface solid dispersion
DOI: https://doi.org/10.31351/vol30iss1pp122-132
122
Solubility and Dissolution Enhancement of Ebastine by
Surface Solid Dispersion Technique
Lina S. Hussein*,1 and Eman B. H. Al-Khedairy**
*Department of Clinical and Laboratory Sciences, College of Pharmacy, Thi-Qar University, Thi-Qar, Iraq
**Department of Pharmaceutics College of Pharmacy, University of Baghdad, Baghdad, Iraq.
Abstract
Ebastine (EBS) is a non-sedating antihistamine with a long duration of action. This drug has
predominantly hydrophobic property causing a low solubility and low bioavailability. Surface solid dispersions
(SSD) is an effective technique for improving the solubility and dissolution rate of poorly soluble drugs by using
hydrophilic-water insoluble carriers.
The present study aims to enhance the solubility and dissolution rate of EBS by using SSD technique. Avicel®
PH101, Avicel® PH 102, croscarmellose sodium(CCS) and sodium starch glycolate (SSG) were used as water
insoluble hydrophilic carriers.
The SSD formulations of EBS were prepared by the solvent evaporation method in different drug: carrier
weight ratios, then evaluated for their percentage yield, drug content, water solubility, release in 0.1 N HCl,
Powder X-Ray Diffraction (PXRD) in addition to Fourier Transform Infrared Spectroscopy (FTIR) for the
determination the drug-carrier interaction.
Most of the prepared SSD formulas showed improvement of drug solubility. The best result was obtained
with formula SSD16 (EBS: CCS 1:15) that showed high percentage yield (98.5%), high drug content (98.39%)
and 8.2fold increase in solubility compared to solubility of pure drug with improved dissolution rate. The drug
was converted to amorphous form without chemical interaction with the carrier. So, it can be concluded that the
solubility and the dissolution rate of EBS were successfully enhanced by SSD technique prepared by solvent
evaporation method using hydrophilic-water insoluble carriers.
Keywords: Ebastine, Surface solid dispersion, Solvent evaporation technique.
تقنية الصلب المنتشر السطحياإليباستين باستخدام تحسين الذوبانية وسرعة تحرر
**الخضيري حازم بكر ايمان و 1 *، نلينا سالم حسي
العراق.، رذي قافرع العلوم السريرية والمختبرية ، كلية الصيدلة ، جامعة ذي قار، *
العراق.، بغداد ، جامعة بغداد ، كلية الصيدلة ، فرع الصيدالنيات **
الخالصة
مما يسبب انخفاض النفور من الماءخاصية له غالبا هذا الدواء .مديد الفعالية مسبب للنعاساإليباستين هو دواء مضاد للهيستامين غير
األدوية ضعيفة الذوبان سرعة تحرر تقنية فعالة لتحسين الذوبان والصلب المتشتت السطحي هي .له التوافر البيولوجي قلة ، وبالتالي ذوبانهقابلية
.محبة للماء-باستخدام مواد غير ذائبة
سيل ييفاإل ، PH101 سيلييفستخدام اإلبا .باستخدام تقنية الصلب المنتشر السطحي إليباستينسرعة تحرراتهدف الدراسة الحالية إلى تعزيز الذوبانية و
PH102، الصلب تم تحضير تركيبات.ت النشا كحامالت مائية غير قابلة للذوبان في الماءيجاليكول الصوديوم للكروسكارميلٌوز وملح الصوديوم ملح
نتاجية ، ومحتوى الدواء ، لإليباستين بطريقة تبخر المذيب في نسب مختلفة من وزن الدواء إلى الناقل وتم تقييمها حسب النسبة اإل السطحي المنتشر
، كما تم فحص خاصية التبلور باستخدام حيود ورمالين 0,1 في حامض الهيدروكلوريك ذو معيارية الدواءر بان في الماء وسرعة تحرقابلية الذو
.تحديد التداخل الحاصل بين الدواء والناقل باستخدام مطياف األشعة تحت الحمراء األشعة السينية و
باستخدام SSD16صيغة تم الحصول على أفضل وقد .باستخدام هذه التقنية الصيغ المحضرة اغلب تحسن في قابلية الذوبان للدواء في أظهرت النتائج
( %98.5نسبة إنتاجية عالية ) التي أظهرت (للكروسكارميلٌوز الصوديوم ملح: اإليباستين) 15:1ملح الصوديوم للكروسكارميلوزر بنسبة الصيغة
مع تحسن في معدل تحرر الدواء . كما أضعاف في الذوبانية مقارنة بالذوبان في الدواء النقي 8,2زيادة قدرها ( و 98.39%، محتوى دواء عالي )
تم تحسينهما بنجاح إليباستينلذلك يمكن االستنتاج أن قابلية الذوبان ومعدل الذوبان لـ .إن الدواء فقد خاصية التبلور بدون تفاعل كيميائي مع الناقل
.هغير قابلة للذوبان في-لماءل محبة المحضرة بطريقة تبخير المذيبات باستخدام مواد صلب المتشتت السطحيال بواسطة تقنية
تقنية التبخر بالمذيبات، الصلب المنتشر السطحي، دواء اإليباستين :المفتاحية الكلمات
Introduction
Solubility is a property of substance in a
particular solvent. In quantitative terms, it is a
concentration of dissolved solute in a saturated
solution at a certain temperature. In qualitative
terms, it means spontaneous interaction of two or
more substances to form one phase, clear
homogeneous molecular dispersion. Dissolution is
the process by which the solute dissociates in a
solvent forming a molecular level, physically and
chemically homogenous dispersion called a
solution. Solubility and dissolution are dissimilar
concepts but are connected.Most of the new drugs
have poor aqueous solubility; thereby have a
difficulty in formulating in drug delivery systems.
1Corresponding author E-mail: ph.lina.salm@gmail.com
Received: 14/8/2020
Accepted:14 /10 /2020
Iraqi Journal of Pharmaceutical Science
https://doi.org/10.31351/vol30iss1pp122-132
Iraqi J Pharm Sci, Vol.30(1) 2021 Ebastine surface solid dispersion
123
Therefore, the enhancement of solubility and
dissolution rate of these drugs are important
preformulation steps in the pharmaceutical product
development research. In general, solubility
difficulties are faced in the class II and class IV of
the Biopharmaceutical Classification System (BCS)
where dissolution becomes the rate limiting step for
the drug absorption (1- 3).
Many techniques have been applied for improving
the solubility of poorly soluble drugs such as salt
formation, converting into prodrugs, micronization
and nanonization, complexation, micelles,
emulsions, solid-lipid nanoparticles, and solid
dispersions. Among these, solid dispersion (SD) is
gaining tremendous significance to enhance
solubility and dissolution of poorly soluble drugs. It
can be defined as molecular mixture of poorly
soluble drugs in hydrophilic carriers. These carriers
play an important role in drug release according to
their properties (4).
Surface solid dispersion (SSD) is another technique
for dispersing one or more active ingredients on a
water insoluble-hydrophilic carrier of extremely
high surface area to achieve increased dissolution
rates and bioavailability of insoluble drugs. When in
contact with water, this carrier disperses
immediately allowing the fast release of the drug.
SSD can overcome some of the disadvantages of the
conventional SDs which prepared by water soluble
carriers like tackiness and difficulty in handling of
the product. Many commonly used excipients like
microcrystalline cellulose, silicon dioxide, sodium
starch glycolate, potato starch and croscarmellose,
have been used as carriers for preparing SSD (5, 6).
Ebastine (EBS) a piperidine derivative, is a non-
sedating antihistamine with a long duration of
action. Chemical structure of EBS is shown in figure
1. It is a basic compound that contains tertiary amine
group with pKa 8.8 and partition coefficient of 7.64.
This drug belongs to BCS class II, thus when
administered orally, it is not readily bioavailable (7,
8).
The objective of this research was enhancing the
solubility and dissolution rate of EBS by SSD
technique, using different hydrophilic-water
insoluble carriers at different ratios.
Figure 1. Chemical structure of Ebastine (9)
Materials and Methods
Materials
Ebastine and Croscarmellose sodium were
purchased from Hangzhou, Hyperchem- China.
Avicel® PH101, Avicel® PH 102 and Sodium
starch glycolate (SSG) were gifted from Pioneer
pharmaceutical company, Iraq.
Methods
Preparation of surface solid dispersion (SSD) of
EBS
Ebastine SSDs were prepared by solvent
evaporation method using different hydrophilic
carriers. Specified amount of the drug was dissolved
in methanol to obtain a clear solution. Then after, an
accurate amount of carrier corresponding to
different drug: carrier w:w ratios were added to the
drug solution (Table 1). The formed suspension was
continuously stirred using magnetic stirrer at room
temperature till all the methanol evaporated. The
dried SSD mass was pulverized and passed through
sieve no. 230. Then they were stored in a desiccator
containing anhydrous calcium chloride as a drying
agent. This agent was used to reduce the humidity in
a desiccator producing a dry environment (at least
24 h) for analysis (10).
Table 1. Composition of different EBS SSD formulas .
Formula
Number
EBS:Carrier
w:w ratio
Ebastine
(g)
Avicel® PH 101
(g)
Avicel® PH 102
(g)
CCS
(g)
SSG
(g)
EBS1
1:1
0.5 0.5 - - -
EBS2 0.5 - 0.5 - -
EBS3 0.5 - - 0.5 -
EBS4 0.5 - - - 0.5
EBS5
1:2
0.5 1 - - -
EBS6 0.5 - 1 - -
EBS7 0.5 - - 1 -
EBS8 0.5 - - - 1
EBS9
1:5
0.5 2.5 - - -
EBS10 0.5 - 2.5 - -
EBS11 0.5 - - 2.5 -
EBS12 0.5 - - - 2.5
EBS13
1:10
0.5 5 - - -
EBS14 0.5 - - 5 -
EBS15
1:15
0.5 7.5 - - -
EBS16 0.5 - - 7.5 -
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Preparation of physical mixture (PM)
Physical mixture was prepared for the
selected SSD formula by mixing the powders
geometrically in a glass mortar using spatula which
was then passed through sieve no.230 then stored in
the desiccator for further use (11).
Evaluation of SSD of Ebastine
Determination of percentage yield
The percent of yield of SSDs was calculated by
using the following Equation (12):
% of yield =
𝐖𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐒𝐒𝐃𝐬
𝐖𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐝𝐫𝐮𝐠+𝐰𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐜𝐚𝐫𝐫𝐢𝐞𝐫
× 𝟏𝟎𝟎
Determination of drug content of SSD
Monitoring drug content uniformity is
required for the control of drug quality and
durability of the process. A precisely weighed
quantity of SSD powder equivalent to 15 mg of EBS
was weighed accurately and dissolved in 30 ml of
methanol. The resulted mixture was filtered through
a 0.45 µm membrane filter then suitably diluted with
methanol. The absorbance of the solution was
measured at 253 nm (13). Experiments were repeated
three times. The percentage of drug content in the
SSD was counted by the following equation (14):
𝐃𝐫𝐮𝐠 𝐜𝐨𝐧𝐭𝐞𝐧𝐭 =
𝐏𝐫𝐚𝐜𝐭𝐢𝐜𝐚𝐥 𝐝𝐫𝐮𝐠 𝐜𝐨𝐧𝐭𝐞𝐧𝐭
𝐓𝐡𝐞𝐨𝐫𝐞𝐭𝐢𝐜𝐚𝐥 𝐝𝐫𝐮𝐠 𝐜𝐨𝐧𝐭𝐞𝐧𝐭
× 𝟏𝟎𝟎
Determination of saturation solubility of SSD
An excess amount of EBS and the prepared
SSDs was added to 10 ml of distilled water in plain
tubes. The test tubes were tightly closed and
continuously stirred on isothermal water bath shaker
for 48 h at 25°C to get equilibrium. Then, a millipore
filter syringe of 0.45 µm was used for filtering the
samples. The dissolved amount was determined by
UV spectrophotometer at 256 nm (15). This study was
done in triplicate.
Determination of hydration capacity
According to the solubility study, one gram
of the best carriers’ formulas was placed separately
in 10 ml pre-weighed centrifuge tube. Sufficient
distilled water was added to make up the volume to
10 ml and the suspension was shaken manually for
5 min. The suspension was allowed to stand for 10
min and then by centrifugation for 15 min at 1000
rpm. Then after, the supernatant was decanted. Then
a tube was reweighed, and hydration capacity was
calculated by using the following equation (16):
𝐇𝐲𝐝𝐫𝐚𝐭𝐢𝐨𝐧 𝐜𝐚𝐩𝐚𝐜𝐢𝐭𝐲 % =
𝐖𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐭𝐮𝐛𝐞 𝐰𝐢𝐭𝐡 𝐬𝐞𝐝𝐢𝐦𝐞𝐧𝐭 −𝐰𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐞𝐦𝐩𝐭𝐲 𝐭𝐮𝐛𝐞
𝐰𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐬𝐚𝐦𝐩𝐥𝐞 𝐨𝐧 𝐝𝐫𝐲 𝐛𝐚𝐬𝐢𝐬
× 𝟏𝟎𝟎
Comparative in-vitro dissolution studies of pure
and SSDs of EBS
The accurately weighed samples
equivalent to 10 mg of EBS were placed in USP type
II dissolution apparatus. In-vitro dissolution study
was done for pure drug, selected SSD formula and
PM. This test was performed using 1000 ml 0.1N
HCl with 100 rpm paddle speed at 37± 0.5 °C. 5 ml
of sample was taken at certain time intervals 10, 15,
20, 30, 40, 50 and 60 min. and substituted with an
equal volume of fresh dissolution medium. After
filtering, the samples were analyzed
spectrophotometrically at 257 nm. The drug
dissolution profile was plotted as percentage of drug
release versus time (17).
Fourier transform infrared (FTIR) analysis
The FTIR spectra of pure drug, the best carrier,
physical mixture PM and the selected SSD
formulation were recorded by using FTIR
(IRAffinity-1) spectrophotometer (Shimadzu,
Japan). The samples were scanned over 4000–400
cm-1 frequency range (18).
Powder X-ray diffraction (PXRD) analysis
The PXRD was used to detect any changes
in the drug crystalline nature and to determine the
possibility of any polymorphic changes of drug in
the SSD formulation that may influence its
dissolution. The X-ray diffractograms of the drug,
the best carrier, PM and optimized SSD formulation
were obtained by using X-ray diffractometer
(Shimadzu, Japan) (19). The scanning speed was
5°/min over a 2θ range of 5–80°.
Statistical analysis
The dissolution profiles were statistically
checked using a similarity factor (f2). This factor
have a value range between 0 and 100. The two
dissolution profiles consider the same when f2
values more than 50 (50– 100); while f2 values less
than 50 indicates that the compared profiles are not
the same. The similarity factor (f2) was defined by
the following equation (20).
f2 = 50 × log {[1 +
1
𝑛
∑ |𝑅𝑡 − 𝑇𝑡|
2
𝑛
𝑡=1
]
−0.5
× 100}
Where (n) is the number of dissolution time points.
(Rt),(Tt) is the reference and test dissolution values
as % at time (t), respectively.
The other results were analyzed using Paired
samples T Test (SPSS) and the level of significance
was set at a p-value of 0.05:
A p value ˃ 0.05 was considered to be non-
significant.
A p value ˂ 0.05 was considered to be significant
Results and Discussion
Percentage yield
High percentage yield was obtained from
all the SSDs formulas that range between 96-99% as
shown in table 2. This indicates that there was no
more than 4% loss in SSD obtained products which
shows the suitability of the solvent evaporation
method in the preparation of EBS SSDs.
Drug content of SSDs
All tested formulations of SSDs showed
acceptable drug content ranging from 97- 99% w/w
as observed in table 2 which was in agreement with
USP requirements (90-110%) (21). These results
indicated a homogeneous distribution of the
prepared formulations.
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Table 2. Percentage yield and drug content of prepared SSDs
Formula Number Formula composition
(Drug: Carrier w:w ratio)
Percentage yield
(PY %)
Drug content
(w/w) (%)
(Mean ±SD), n=3
SSD1 (1:1EBS:Avicel®PH101) 96.2 98.67±1.95
SSD2 (1:1EBS:Avicel®PH102) 96 99.68 ± 4.15
SSD3 (1:1EBS:CCS) 99.9 99.82±2.40
SSD4 (1:1EBS:SSG) 99.3 98.39±5.87
SSD5 (1:2EBS:Avicel®PH101) 98.4 98.38±1.39
SSD6 (1:2EBS:Avicel®PH102) 95.5 99.80±3.44
SSD7 (1:2EBS:CCS) 98.7 98.24± 3.25
SSD8 (1:2EBS:SSG) 97 98.68±1.52
SSD9 (1:5EBS:Avicel®PH101) 98.4 98.67±1.64
SSD10 (1:5EBS:Avicel®PH102) 97.5 98.96±3.37
SSD11 (1:5EBS:CCS) 99.2 97.23 ±1.14
SSD12 (1:5EBS:SSG) 98.8 99.82±0.44
SSD13 (1:10EBS:Avicel®PH101) 98.2 99.69±4.24
SSD14 (1:10EBS:CCS) 99.4 98.24±4.24
SSD15 (1:15EBS:Avicel®PH101) 96.9 99.68± 3.07
SSD16 (1:15EBS:CCS) 98.5 98.39±6.64
Saturation solubility of EBS SSDs
Most of the prepared SSDs of EBS showed
a significant improvement in their water saturated
solubility compared to that of pure drug as shown in
table 3. This could be due to the hydrophilic nature
of these carriers and surface adsorption of drug
particles on these carriers in an extremely fine state
of subdivision or molecular form. The resulting
decrease in particle size and the increase in the
interfacial area of contact between the drug particles
and the solvent increased the solubility of the drug
compared to the drug alone. In addition, the affinity
between the hydrophilic inert carriers and the
solvent facilitated the penetration of the solvent into
the particles that resulted in further enhancement of
the solubility of drug (22-24).
This enhancement was affected by the type of the
carrier and drug: carrier ratio. Table 3 showed that,
no improvement in the solubility of EBS was
obtained by using 1:1 drug: carrier w:w ratio, but
significant enhancement in drug solubility (p<0.05)
at 1:2 ratio in the following sequence:
CCS (SSD7) < Avicel® PH101 (SSD5) < SSG
(SSD8) < Avicel® PH102 (SSD6)
Also, it was found that the saturated solubility of
EBS increased significantly (p > 0.05) with an
increase in drug: carrier ratio from 1:2 to 1:5 for all
the used carriers with exception of SSG. A higher
amount of the carrier resulted a larger amount of
EBS dispersed over the carrier surface and hence
improved EBS wettability and solubility (25).
Among carriers were CCS and Avicel® PH101
exhibited highest improvement of solubility at 1:5
drug: carrier ratio in comparison with the others,
since they produced 3.5, 2.9 folds increase in
solubility, respectively.
The small particle size of CCS ( ̴ 50µm), Avicel®
PH101( ̴ 50µm) compared to Avicel ®PH 102 (100
µm( resulted in a larger surface available for
adsorption of the EBS particles which would
provide better drug wetting ability associated within
them (10, 26, 27).
On the other hand, SSG with very small particle size
(38 µm), although it increased the saturated
solubility compared to the pure drug, but there was
no significant (p < 0.05) improvement in the
saturated solubility by increasing the proportion of
this carrier from 1:2 (SSD8) to 1:5 (SSD12). This
was due to enough surface area of SSG for all drug
particles at ratio 1:2 w:w drug: SSG so that, further
increase in SSG at 1:5 ratio was of no benefit
because all drug particles adsorbed and no more was
available for extra adsorption (10, 28).
Therefore, CCS and Avicel® PH101 were chosen
preferably for SSDs preparation to proceed with this
study. The results of the solubility study showed that
an increase in the CCS ratio (1:10 and 1:15) lead to
EBS solubility improvement (6.3folds and 8.2folds,
respectively as compared with the solubility of pure
EBS). While the results of Avicel® PH101 showed
the higher improvement of drug solubility occur
with 1:10 ratio SSD13 (3.4 folds) in comparison to
1:15 ratios SSD15 (3 folds). These results might be
due to the differences in their hydration capacity.
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126
Table 3. The saturated solubility of EBS SSDs prepared with several Drug:Carrier w:w ratios in distilled
water at 25˚C.
Formula Number Formula Composition
(Drug: Carrier w:w ratio)
Saturation solubility
mg/ml
(Mean ±SD ), n=3
Pure EBS 0.0017±0.0004
SSD1 (1:1EBS:Avicel®PH101) 0.0017±0.0008
SSD2 (1:1EBS:Avicel®PH102) 0.0018±0.0009
SSD3 (1:1EBS:CCS) 0.0018±0.0001
SSD4 (1:1EBS:SSG) 0.0020±0.0001
SSD5 (1:2EBS:Avicel®PH101) 0.0031±0.0001
SSD6 (1:2EBS:Avicel®PH102) 0.0022±0.0004
SSD7 (1:2EBS:CCS) 0.0036±0.0003
SSD8 (1:2EBS:SSG) 0.0023±0.0001
SSD9 (1:5EBS:Avicel®PH101) 0.0050±0.0001
SSD10 (1:5EBS:Avicel®PH102) 0.0026±0.0002
SSD11 (1:5EBS:CCS) 0.0060±0.0001
SSD12 (1:5EBS:SSG) 0.0021±0.0002
SSD13 (1:10EBS:Avicel®PH101) 0.0058±0.0003
SSD14 (1:10EBS:CCS) 0.0107±0.0006
SSD15 (1:15EBS:Avicel®PH101) 0.0051±0.0001
SSD16 (1:15EBS:CCS) 0.0140±0.0001
Hydration capacity
Hydration capacity test is an indicator of
swelling power or for extent of solid- liquid
interaction. The carriers under this test were wetted
by water and then evaluated for their water holding
capacity. The capacity of CCS was found to be
73.92% which was superior to Avicel® PH101
(34.95%). This result confirmed the previous results
about the superiority of CCS over Avicel® PH101
in enhancing the solubility of drug as it absorbed
more water so it exhibited more wetting effect (29).
Comparative in-vitro dissolution studies
The formulas SSD14 (1:10) and SSD16
(1:15) Drug: CCS ratio were used to study the effect
of CCS ratio on in-vitro dissolution profile of EBS,
since the highest solubility was obtained by them.
Figure 2 demonstrated that both formulas improved
dissolution rate in 0.1 N HCl in comparison to the
pure drug. The dissolution profiles for both ratios
(1:10 and 1:15 drug: carrier) were almost similar
(f2=77.21) so that, no further enhancement in
dissolution was obtained with an increased in carrier
ratio. The dissolution enhancement effect might
belong to high swelling, wicking and hydration
capacities of the CCS particles that would prevent
aggregation of the drug particles and facilitated
dissolution (30). It was observed that drug: CCS ratio
of 1:10 was sufficient to adsorb the drug and
improve the dissolution process as that for 1:15 ratio
(31).
Figure 2. Effect of carrier ratio of SSD on the in-
vitro dissolution of EBS in 0.1N HCl at 37±0.5°C.
Although both SSD14 and SSD16 highly improved
the dissolution of EBS, but SSD16 produced more
enhancement in solubility than SSD14 (8.2 folds
versus 6.3 folds). So that, SSD16 (EBS:CCS 1:15)
was selected to be the optimized SSD on the basis of
highest drug solubility and improved dissolution of
drug.
As well as, the efficiency of SSD technique was
demonstrated by comparing the dissolution profile
of SSD16 with that of PM and of pure EBS as shown
in figure 3. The profile showed that the dissolution
rate of EBS in PM as well as in SSD was higher as
compared to that of pure EBS. The similarity factor
f2 was found to be equal to 9.02 and 40.56 in
comparison of SSD16 formula and its PM to pure
drug sequentially.
The dissolution of pure EBS was found to be 25.81%
within 60 min whereas, 44.17% of EBS was released
Iraqi J Pharm Sci, Vol.30(1) 2021 Ebastine surface solid dispersion
127
after 60min from the PM. This might be due to the
hydrophilicity of CCS in the respective mixture
which rendered this mixture hydrophilic and
enhanced the wettability and solubility of drug as
indicated from its saturated solubility which was
found to be higher than pure drug (0.0103±0.0001
mg/ml versus 0.0017±0.0004 mg/ml) , yet it was
significantly (p<0.05) lower than its corresponding
SSD (29, 32, 33).
On the other hand, the % release of EBS from the
SSD16 was increased to 93.19% within 60 min. So
that, SSD was an efficient technique to improve the
dissolution rate of EBS which might be attributed to
a reduction of its particle size and its deposition on
the surface of a hydrophilic carrier (34).
Figure 3. Comparative in-vitro dissolution profile
of the pure EBS, SSD16 and physical mixture of
SSD16 (PM) in 0.1N HCl at 37±0.5 °C.
Fourier Transforms Infrared Spectroscopy (FTIR)
The FTIR spectrum of pure EBS and CCS
are shown in figures (4) and (5), respectively. The
FTIR spectrum of EBS exhibited characteristic
bands at 3051 cm-1 for C-H stretching of the ring,
2943,2916, 2819 cm-1 for CH-stretch of ( CH3 and
CH2), also strong and sharp band at 1678 cm
-1 for
ketonic carbonyl group (C=O stretch), 1454 cm-1 for
aromatic C=C stretch of phenyl ring, and C-N
stretching at 1269cm-1. These results were in
agreement with the previous studies (35-37).
The FTIR spectrum of CCS exhibited characteristic
bands at 3360 and 3240 cm-1 for alcoholic O-H
groups, 2904 cm-1 for aliphatic C-H stretching of
(CH2), and weak band at 1732, 1720 cm
-1 for C=O
of carboxylic groups. These results were in
consistent with the previous studies (35, 38).
The FTIR spectra of PM and that of the selected
SSD16 formula (Figure 6 and 7) showed mostly the
characteristic peaks of CCS, that overwhelmed the
peaks of EBS, as CCS was mixed at a ratio of 1:15
(EBS:CCS). The only characteristic peak of ketonic
carbonyl group (C=O stretch) for EBS was observed
in the same position in both figures with low
intensity due to dilution of drug with the high
amount of CCS. The absence of new peaks in SSD16
spectrum confirmed absence of chemical
interaction.
Figure 4 .FTIR spectrum of EBS
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Figure 5. FTIR spectrum of CCS
Figure 6. FTIR spectrum of PM
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Figure 7. FTIR spectrum of SSD16
Powder X-ray diffraction (PXRD)
The PXRD patterns of EBS, CCS, PM and
SSD16 are shown in figures (8-11), respectively.
The diffraction pattern of the pure EBS showed a
highly crystalline nature, indicated by numerous
intensive peaks at a diffraction angle of 2θ (5.84°,
11.54°, 18.68°, 19.06°, 19.39°) throughout the
scanning range. These values approached the
previously reported data (36, 39). On the other hand,
the CCS diffractogram did not show sharp peaks, but
only some peaks with low intensity at 18.41°, 22.9°,
43.95°, 64.29°, 77.38° related to its amorphous
nature (40).
The characteristic peaks identified in the EBS
PXRD were not detected neither in PM nor in
SSD16 PXRD patterns whereas, peaks
corresponding to the CCS were still present in both
of them, indicating the predominant effect of the
high amount of the carrier in this formula. The broad
shape with further decrease in intensity observed in
SSD16 PXRD pattern compared to that of PM may
be explained by the conversion of the drug to an
amorphous form, which contributed to the
enhancement of its solubility (41, 42).
Figure 8. PXRD diffractogram of EBS
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Figure 9. PXRD diffractogram of CCS
Figure 10. PXRD diffractogram of PM
Figure 11. PXRD diffractogram of SSD16
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Conclusion
An improvement in the solubility and
dissolution rate of EBS, a poorly water soluble drug,
was successfully obtained by surface solid
dispersion technique using CCS as a hydrophilic
water insoluble carrier at a ratio of 1:15 EBS:CCS.
The enhanced wettability, decrease in particle size,
increase the interfacial contact between the drug and
the solvent accompanied with decrease crystallinity
were the most important factors resulted in
improvement of solubility and dissolution.
Acknowledgement
The authors are grateful to acknowledge
the College of Pharmacy -University of Baghdad for
providing the necessary facilities to carry out this
work. The authors are also thankful to Pioneer
Pharmaceutical Company, Iraq, for their generous
help for providing gift samples of required
materials.
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