Applied Clay Science 116117 (2015) 193201

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Applied Clay Science

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Research paper

Characterization of Iranian bentonites to be used as

pharmaceutical materials
Soroush Modabberi a,, Alireza Namayandeh a, Alberto Lpez-Galindo b, Cesar Viseras b,c,
Massimo Setti d, Mohsen Ranjbaran a
a

School of Geology, University of Tehran, Enghelab Square, P.O. Box 14155-6455 Tehran, Iran
Instituto Andaluz de Ciencias de la Tierra (CSICUniversidad de Granada), Avda. de las Palmeras, 4, 18100 Armilla, Granada, Spain
Dpto. Farmacia y Tecnologa Farmacutica, Facultad de Farmacia, Universidad de Granada, Spain
d
Dipartimento di Scienze della Terra e dell'Ambiente, Universit di Pavia, Via Ferrata 1, 27100 Pavia, Italy
b
c

a r t i c l e

i n f o

Article history:
Received 29 November 2014
Received in revised form 11 March 2015
Accepted 14 March 2015
Available online 15 April 2015
Keywords:
Iranian bentonites
Montmorillonite
Pharmaceutical formulations
Trace elements
Thixotropy
Excipients

a b s t r a c t
Ten Iranian bentonites, sampled from the deposits of Chah-Golestan, Chah-Pirouz, Chah-Keshmir and Chah-Taleb
(Sarayan), Gholeh-Gelia and Kharman-Sar (Ferdows, Khorasan), Mehrejan (Khoor) and Manian (Zagros) were
analyzed to evaluate their potentialities as pharmaceutical products. The mineralogy, chemistry, pH, microbial
content, powder ow characteristics, swelling capacity, cation exchange capacity, specic surface area, sedimentation volume, and rheological properties of all samples were determined. The bentonite located in carbonate
rocks (Zagros) is made up of calcium montmorillonite (97%) and quartz (3%). The rest of the bentonites are
hosted by Eocene volcanic rocks and are mainly made up of sodium montmorillonite (47%84%) and cristobalite
(up to 39%), with lesser quantities of quartz, calcite, plagioclase, zeolites and halite. Two of the samples (those
located at Manian and Chah-Golestan C) showed appropriate composition, purity and technical properties to
be used in pharmaceutical applications, whereas the rest would require purication or improvement of their
properties. In particular, the samples could be used for topical dosage forms as rheological additives.
2015 Elsevier B.V. All rights reserved.

1. Introduction
Clay minerals are among the mostly used minerals in numerous applications. The most common uses are foundry sand bonds, drilling
mud, ceramics, ltration, and iron ore pelletizing (Allo and Murray,
2004). Since early times various types of clay minerals have been used
in the traditional medicines of most countries. The term bentonite is
used in the industry for clays mostly composed of smectite group minerals (Grim and Guven, 1978). However in pharmaceutical literature,
bentonite is used to refer to a natural, colloidal, hydrated aluminium
silicate (Viseras et al., 2006; USP 36NF 31, 2013). The main minerals
of the smectite group are calcium montmorillonite, sodium montmorillonite, saponite, nontronite, hectorite, and beidelite (Murray, 2007). The
colloidal size and structure of smectite minerals mean that they have a
wide range of applications in industry as a result of their rheological
properties, absorbing capacity, plasticity, high specic surface area,
CEC and swelling properties. Among all members of clay minerals, calcium and sodium montmorillonites are among the most frequently used
of all the clay minerals (Grim, 1962; Hartwell, 1965; Grim and Guven,
1978; Elzea and Murray, 1990; Harben and Bates, 1990; Konta, 1995;

Corresponding author. Tel.: +98 21 61112985, +98 9122145463 (cellphone).

E-mail address: modabberi@ut.ac.ir (S. Modabberi).

http://dx.doi.org/10.1016/j.clay.2015.03.013
0169-1317/ 2015 Elsevier B.V. All rights reserved.

Luckham and Rossi, 1999; Allo and Murray, 2004; Eisenhour and
Brown, 2009; Guven, 2009; Abdel-Motelib et al., 2011; Agha et al.,
2012). Because of these various properties, bentonites are being used
in an increasing number of applications, especially in the pharmaceutical industry (Williams et al., 2009; Abdel-Motelib et al., 2011; Carretero
et al., 2013) and in pleotherapy and medical applications (Summa and
Tateo, 1998; Cara et al., 2000; Veniale et al., 2004, 2007; Tateo and
Summa, 2007; Carretero et al., 2010, 2014; Karakaya et al., 2010;
Gomes et al., 2013).
The mineralogical and chemical compositions of bentonites depend
on their evolution from parent rocks. Hence, their chemical composition
and physical properties should be determined carefully before any
usage, especially in cosmetic and pharmaceutical purposes, and special
precautions should be taken (Lpez-Galindo et al., 2007), given that a
clay mineral must comply with several chemical, physical, and toxicological requirements for use in pharmaceutical formulations, depending
on whether the purpose is therapeutic or cosmetic.
2. Geological setting
Iranian bentonite deposits occur in six zones (SemnanToroud,
AlborzAzerbaijan, Eastern Iran, Central Iran, TafreshTakab and
Zagros), mostly in connection with Tertiary magmatism (Hejazi and
Ghorbani, 1994).

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S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

Fig. 1. Locations of the studied samples (red stars) on a geological map of Iran after Stocklin (1968) and Nabavi (1976).

S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

The deposits in Eastern and Central Iran are hosted by Eocene volcanic rocks and it has been suggested that they are of diagenetic origin,
subsequent to the eruption and deposition of tuff and volcanic ash in a
shallow aqueous environment like a lagoon (Abedini et al., 2011;
Namayandeh, 2011; Namayandeh et al., 2012). The Manian deposit is
located in the carbonate rocks of the Zagros orogen, with no volcanic activity throughout its long geological history.
About 70 bentonite mines and occurrences have been identied in
Iran, of which 59 mines are in operation producing about 400,000 t/y.
50% of the mined bentonite is used in the oil industry for deep well drilling. The remaining 50% is used in the ceramics, paint and rening industries (Namayandeh, 2011).
Eight bentonite mines were studied in this research, including
Chah-Golestan (SGA, SGB, SGC samples), Chah-Pirouz (SP), ChahKeshmir (SK) and Chah-Taleb (ST) in Sarayan (Eastern Iran), and
Gholeh-Gelia (FGH) and Kharman-Sar (FKH) in Ferdows, South Khorasan province (Eastern Iran zone); one mine (Mehrejan, EM) is located in Khoor, Central Iran and one mine (Manian, JM) is located in
Jahrom, Zagros (Fig. 1).
The bentonite deposits of Iran, except that of Manian, are associated
with stratabound-type volcanic rocks, and include thin gypsum layers
(average thickness of 2 cm). The alteration of volcanic rocks to bentonite is irregular, and is more intense in some deposits such as ChahPirouz and Chah-Taleb, which show pervasive calcication, silicication
and traces of Fe oxy-hydroxides. The color of the bentonite varies locally, with white, green, red, and pink bentonites observed at the quarry
face. However, because of percolation of Fe-bearing solutions, most
quarry faces are red in color.
Chah-Golestan deposit is the biggest bentonite mine in Eastern Iran
deposits, and Manian deposit is located in OligoceneMiocene
carbonate rocks, with a 0.51 m layer of green-colored bentonite,
which is mined in small scale by underground mining techniques
(Namayandeh, 2011).
3. Materials and methods
Ten representative samples averaging 1 kg in weight, were collected
from the different mines. Three samples were taken from the Chah
Golestan deposit because of the variety of bentonite types observed
there. Samples were powdered to b20 m, dried at 65 C, and kept in
a desiccator for at least 48 h before testing.
Macroscopic observation showed all samples to be ne-grained, homogeneous and generally light-colored: white (SP, SK, ST, FGH, SGB),
beige (EM, JM, FKH) or pink (SGA, SGC).
3.1. Mineralogy and chemistry
The mineralogical analyses were carried out using X-ray powder
diffractometry (XRPD) on natural samples, and after the standard
treatments for the identication of the clay minerals: ethylene
Table 1
Mineralogical composition of the studied samples, and d(001) spacing of montmorillonite.

Montmorillonite
Illite
Kaolinite
Quartz
Plagioclases
Cristobalite
Calcite
Clinoptilolite
Halite
Montmorillonite
d(001) (natural
smectite)
d(001) (glycol)

SGA

SGB

SGC

SK

SP

ST

FGH FKH

EM

JM

73

56

25
3
13

84

5
6

65

34

60

39

71

26

70

2
3
25

47
11
15
3
10
7
5

97

25
1

68

1
9
11
9
2

12.4 12.4 12.3 12.5 12.4 12.4 12.2 12.4 12.4 15.1
16.8 16.9 17

16.9 16.8 16.9 16.9 16.9 16.9 16.7

195

glycol saturation for the identication of the swelling clay minerals

and heating at 550 C in oriented aggregates. The analyses were carried out at the University of Pavia using the following instrumental
features: PW1800/10 Philips X-ray Diffractometer and X'Pert High
Score v. 1.0b (Philips) software, Cu K radiation, graphite monochromator, automatic divergence slit, 45 kV, 35 mA, scan interval
from 2 to 65 2, and a scan speed of 0.02 2/s. The results from
the XRPD analyses were compared with those in the ICDD (International Centre for Diffraction Data) database and with our own
reference standards, to obtain a qualitative evaluation of the mineralogical composition of the samples. Semi-quantitative analyses
were performed following Moore and Reynolds (1989), and the
nal contents of the different mineral phases were calculated by
combining XRD and chemical analytical data, following Torres-Ruiz
et al. (1994) and Lpez-Galindo et al. (1996).
The elemental compositions of bulk samples were analyzed using a
commercial wavelength dispersive X-ray uorescence instrument
(BRUKER S4 Pioneer) equipped with an Rh anode X-ray tube (60 kV,
150 mA); three analyzer crystals (OVO-55, LiF 200 and PET) and a
ow proportional counter for light element detection and a scintillation
counter for heavy elements in the same laboratory. Quantication was
made by the fundamental parameter method using Spectra Plus software linked to a BRUKER S4 Pioneer instrument. Five grams of each
powdered sample was mixed with 0.5 g of a binder (Hoechst wax C
micropowder) and homogenized in an agate mortar. A small aluminium
sample holder about 4 cm in diameter was used to obtain an XRF-pellet.
The pellets were pressed at 90 bars for 30 s in a Nannetti hydraulic press.
Samples were heated to 900 C for 1 h to determine loss on ignition
(LOI).
Trace elements were determined using inductively coupled plasmamass spectrometry (ICP-MS) in the AMDEL Labs Corp, Australia.
Scanning electron microscope (SEM) observations were performed
using a LEO 1430VP ZEISS system equipped with microanalysis (Centro
de Instrumentacin Cientca, Granada University). Samples were
graphite-coated before analysis.
3.2. Microbiological tests
In order to determine the hygienic quality of the bentonites a prerequisite for their eventual use for purposes of human health samples
were tested for the presence of some microorganisms (Escherichia coli,
Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans)
(Viseras and Lpez-Galindo, 1999; Viseras et al., 2006; Abdel-Motelib
et al., 2011; EP 7.0, 2011; USP 36NF 31, 2013). The culture and method
of preparing suspensions were adapted from Viseras et al. (2006).
3.3. Pharmacopoeial tests
3.3.1. Methylene blue adsorption
Samples can be classied according to their ability to adsorb this dye
and, indirectly, their ability to retain micro-organisms, following the
methodology described in USP 36NF 31 (2013).
Table 2
Structural formula (per half unit cell) of Iranian montmorillonites.
Tetrahedral
sheet

SGA
SGC
SK
SP
ST
FGH
JM

Si

IV

3.92
3.80
3.96
3.98
3.98
3.87
3.87

0.08
0.20
0.04
0.02
0.02
0.13
0.13

Al

Octahedral sheet
VI

Interlayer

Al

Mg

Fe

Ti

Ca

Na

1.36
1.34
1.50
1.44
1.45
1.35
1.39

0.27
0.30
0.33
0.28
0.31
0.31
0.57

0.24
0.27
0.12
0.16
0.10
0.20
0.12

0.01
0.02
0.00
0.02
0.00
0.02
0.01

0.01
0.04
0.02
0.03
0.02
0.06
0.18

0.04
0.02
0.05
0.07
0.06
0.07
0.12

0.58
0.59
0.41
0.45
0.58
0.55
0.01

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S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

The methylene blue adsorption test is also used to determine the

cation exchange capacity (CEC) and specic surface area (SSA) of clays
in many industrial applications (ASTM, 2003). The blue halo method
was carried out on all samples to calculate these parameters (Kahr
and Madsen, 1995; Viseras and Lpez-Galindo, 1999; ASTM, 2003;
Yukselen and Kaya, 2008; Abayazeed and El-Hinnawi, 2011).
All bentonites have been saturated in sodium. So, 2, 4 and 6 g of sodium carbonate were added to clay suspensions and methylene blue adsorption was measured after 24 h repose.
3.3.2. pH measurement
According to pharmacopoeial specications for bentonite (USP 36
NF 31, 2013), the pH values of clay water suspensions (2 g/50 mL)
were measured after 2 min of continuous stirring.
3.3.3. Powder ow characteristics
As an indirect method to address the ow characterization, the pharmacopoeias commonly propose the measurement of bulk density (EP
7.0, 2011; USP 36NF 31, 2013). Bulk density (b) was measured by
pouring samples slowly into a 250 mL calibrated measuring cylinder
through a funnel at a xed height above the cylinder. The tapped density (t) was determined after 1250 taps using a pharmacopoeial tapping
density tester (Pharma test, model PT-TD200, Germany). Three replicates were carried out for each measurement and results were
averaged. The Carr index (CI) (Carr, 1965) and Hausner ratio (HR)
(Hausner, 1967) were calculated from bulk and tapped density, using

Eqs. (1) and (2), respectively, and the calculated values were used to
quantify powder ow (Wells and Aulton, 2007; Rebelo et al., 2011).

CI



t b
100
t

HR

t
b

3.3.4. Swelling capacity

Swelling capacity of the samples was determined by measuring the
sediment volumes obtained after 2 h of repose from dispersions prepared by slowly pouring (20 mg every 2 min) 2 g of powder sample in
100 mL of distilled water.
3.3.5. Sedimentation volume
Sedimentation volumes were measured according to EP 7.0 (2011).
Briey, 100 mL of clay suspensions (3% w/v) in distilled water was prepared by using a Silverson L5M stirrer (SILVERSON) at 5000 rpm for
20 min and then stored undisturbed at room temperature for 24 h in
stoppered testing tubes. The nal volumes were then recorded and
the corresponding sediment volumes (Sv) calculated as the ratio between the sediment's nal volume in mL (V24) and the original volume
(in mL) of the sample dispersions before settling (V0).

Table 3
Chemical composition of the studied samples.
SGA
Major elements (%)
SiO2
Al2O3
Fe2O3
MgO
CaO
Na2O
K2O
TiO2
P2O5
MnO
Cl
LOI
Total
Trace elements (ppm)
As
Pb a
Hg
Mo
Co
Tl
Ba
Cr
Cu
Ni
Li
Sn
V
Zn
Be
Cs
Sc
Sr
Th
U
Zr
a
b

SGB

SGC

SK

SP

ST

FGH

FKH

EM

JM

63.81
11.76
3.10
1.75
0.92
2.90
0.09
0.19
0.02
0.01
0.85
14.60
99.99

65.09
12.10
1.84
2.08
2.61
1.95
0.41
0.29
0.03
0.03
0.30
13.10
99.81

48.14
15.56
4.09
2.29
3.58
6.06
0.33
0.34
0.04
0.02
2.11
17.80
100.35

68.22
11.27
1.38
1.90
0.37
2.36
0.12
0.01
0.03
0.01
0.78
13.50
99.95

70.36
9.75
1.68
1.46
0.48
2.86
0.16
0.16
0.02
0.01
0.83
11.80
99.57

60.44
10.78
1.20
1.82
0.64
4.60
0.13
0.01
0.02
0.02
1.86
18.50
100.02

65.15
12.48
2.55
1.98
0.60
2.71
0.46
0.29
0.04
0.01
0.83
12.80
99.89

51.26
13.81
4.77
3.01
6.07
2.83
0.92
0.86
0.26
0.04
0.10
15.70
99.63

52.01
17.56
3.55
1.68
3.45
4.02
1.89
0.82
0.21
0.03
1.20
13.60
100.01

52.19
16.42
2.00
4.85
1.47
0.06
1.82
0.19
0.04
0.00
0.00
20.50
99.53

3.9
4.4
0.05
0.4
3.2
b0.1
791
2.0
12
6
b0.5
4.5
8
76
1.9
5.8
6.0
146
23
4.0
194

7.5
11.9
0.05
0.3
3.5
b0.1
578
7.0
8
5
b0.5
3.4
23
54
2.8
11.8
8.0
231
21
6.4
153

3.4
4.7
0.05
0.4
7.2
0.1
19
2.0
9
7
b 0.5
4.4
14
102
2.6
2.7
10.0
94
22
5.3
333

3.9
13.7
0.05
0.1
0.7
0.1
258
2.0
5
b2
b0.5
6.7
77
58
4.5
4.8
3.0
57
10
1.3
70

7.4
21.4
0.05
0.4
0.4
b0.1
744
2.0
2
b2
b0.5
3.6
7
188
2.3
3.4
7.0
100
21
2.3
152

3.5
40.3
0.05
0.5
3.9
b0.1
388
2.0
6
b2
b0.5
7.7
2
80
6.4
4.3
4.0
44
13
1.9
79

1.8
18.7
0.05
0.9
4.8
0.1
320
10.0
5
8
b0.5
4.0
20
61
2.1
7.6
6.0
120
20
4.7
185

3.5
13.3
0.06
1.2
15.2
0.3
469
44.0
24
41
b0.5
2.1
164
68
1.6
8.3
11.0
116
11
2.0
206

18.0
24.0
0.05
1.3
9.0
0.6
253
12.0
27
13
b0.5
1.7
73
79
2.3
15.2
8.0
234
7
2.4
161

6.3
6.7
0.05
0.5
3.8
0.2
490
16.0
10
124
b0.5
2.4
123
26
0.8
30.3
5.0
254
18
0.9
113

Heavy metals assay in European Pharmacopoeia match to Pb determination (EP 7.0, 2011).
Oral limits in drug products, drug substances and excipients, accordingly to Table A.2.2 of the Q3D guide.

Acceptable limit (ppm)

8
50
1
18
5
0.8
1300
1100
130
60
78
640
12
Low inherent toxicity

Normative
EP, USP
NHPD
ICH b

Not safety concerns according to

referred normatives

S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

3.3.6. Rheological properties

Clay/distilled water suspensions (33% w/v) were prepared by using
a Silverson L5M stirrer (SILVERSON) at 5000 rpm for 20 min. Each
clay suspension was subjected to a complete rheological characterization by means of a Haake Rotovisco R1 (Haake instruments, Ltd,
Germany), equipped with a plateplate combination (P20 Ti L S) as a
measuring system. All measurements were carried out at 25.0
0.1 C, after a rest time of 3 min. Steady-shear ow tests were performed
over the range of shear rates from 1.0 to 100 s1 (upwards). Downward
curves (100 to 1.0 s1) were also determined to evaluate the existence
of thixotropy. Tests were carried out in automatic mode to ensure that
steady state at each shear rate was reached. The tests were done at
least in triplicate.
4. Results and discussion

197

7.0, 2011; USP 36NF 31, 2013; Snchez-Espejo et al., 2014a). In the remaining samples, mineral impurities, particularly crystalline silica such
as quartz and cristobalite, must be removed from the bentonites before
eventual pharmaceutical applications, in order to prevent carcinogenic
and other effects. The amounts of such compounds should be controlled
and their use avoided as far as possible in the pharmaceutical industry
(IARC, 1997, 2012), even though the association of quartz with clay minerals inhibits most adverse effects (Schins et al., 2002; Creutzenberg
et al., 2008).
Table 2 (half unit cell) tentatively includes the structural formulae of
dioctahedral smectites in more pure samples, as deduced from chemical
analysis once the contributions of Si from quartz and cristobalite, and Ca
from calcite and Na from halite have been eliminated. The results of the
formulae suggest that montmorillonite composition prevails over
beidelite and other smectites.

4.1. Mineralogy
4.2. Chemistry
The main mineral phases found in eastern Iranian bentonites
(Sarayan and Ferdows) are sodium dioctahedral smectites (main XRD
peak around 12.4 , (060) reection at 1.50 ) (b84%), and cristobalite
(b39%). Calcite (19%) is present in Chah-Golestan and Kharman-Sar
deposits, plagioclases (39%) were detected in Ferdows deposits, and
quartz, halite and zeolites were also found in some of these deposits,
normally in very low quantities (Table 1). The only exception was sample SGB, containing 13% clinoptilolite.
The sample from central Iran (EM) showed a varied clay association,
including sodium smectite (47%), kaolinite (15%) and illite (11%). Plagioclases, cristobalite, calcite, quartz and halite were also present.
The Zagros sample (JM) was a practically pure calcic dioctahedral
smectite, with only 3% quartz. It was the only smectite showing a diffraction peak at 14.2 .
Only samples JM and SGC fulll the pharmaceutical requirements together with mineralogical composition (Lpez-Galindo et al., 2007; EP

Data on the major and trace element contents are included in

Table 3. Although according to the European and USA pharmacopoeias
(EP 7.0., 2011; USP 36NF 31, 2013), special attention must be paid to
the Pb and As contents, we also took into consideration the acceptable
limits of other elements proposed for clays recommended for topical
products by the Natural Health Product Directorate (NHPD, 2013) and
those included in the Guideline for elemental impurities in drug products, recently issued by the International Conference of Harmonization
(ICH, 2013) (resumed in Snchez-Espejo et al., 2014b).
The maximum permissible lead content in bentonite is considered to
be 50 ppm, and that of arsenic 8 ppm. All samples fulll the pharmacopoeial requirements for Pb, and sample EM exceeds the permissible
amount of As. The content of the rest of trace elements is within the
acceptable limits.
When we compared the data from Iranian bentonites with those
found in clays used in herbalist's shop or in pharmacies (Mascolo
et al., 1999) or proposed to be used for human health (Viseras and
Lpez-Galindo, 1999; Tateo et al., 2001, 2006; Mascolo et al., 2004;
Viseras et al., 2006; Snchez-Espejo et al., 2014b), we found similar
values for almost all elements (Fig. 2 and Table 3), with the exception
of very high Zn content in SP and SGC samples, and very high Ni content
in JM and FKH samples. It can be concluded that elemental impurities
should be always controlled within acceptable limits in health care
products, as well as the inuence of possible routes of administration
in the bioavailability of a particular impurity to provide route specic
safety assessment, as for instance it is the case for V, which is present
in relative high amount in samples FKH and JM. Vanadium has been
reported to have potentially benecial effects in treatment of several
diseases and it is included in dietary supplement. Nevertheless, as V
can exist in a variety of oxidation states, some of them may be toxic
(ICH, 2013).

Table 4
Microbial analysis (no. UFC/g sample).

Fig. 2. Compositional range of selected trace elements in the studied samples (boxes), and
comparison between the average of Iranian bentonites and average of published data for
health product bentonites.
Data from Mascolo et al. (1999), Viseras and Lpez-Galindo (1999), Viseras et al. (2006),
Snchez-Espejo et al. (2014b).

Escherichia Staphylococcus Pseudomonas Total

Sample Total
coli
aureus
aeruginosa
spores
aerobic
microbial

Candida
albicans

SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JM

A
A
1
A
A
A
A
A
A
A

A
A
100
100
500
500
100
100
3000
200

A
A
A
A
A
A
A
A
A
A

A
A
A
A
A
A
A
A
A
A

A
A
A
A
A
A
A
A
A
A

A
A
A
A
A
A
A
A
A
A

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S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

4.3. Microbial analysis

The microbial study revealed that all samples were free from pathogenic bacteria (Table 4), and the total amount of microorganisms was
consistent with the pharmaceutical requirement (EP 7.0, 2011). The
limit for total aerobic microbial count is 103 CFU/g in non-sterile substances for pharmaceutical use, whereas for non-sterile oral dosage
forms containing raw materials of natural (animal, vegetal or mineral)
origin it increases to 104 CFU/g, reaching 105 CFU/g in some herbal
medicinal products. Similarly, the limit for combined yeasts/molds is
in the range 102104 CFU/g, depending on the nature of the starting material and the manufacturing process. Sterilization is recommended for
sample EM, which showed relatively high total aerobic bacteria when
compared with the other samples (3000 UFC/g), and also for the SGC
sample, which was the only one contaminated with C. albicans.
4.4. Morphology and texture
SEM micrographs show that all samples are characterized by the
presence of pseudo-spherical smectite aggregates ranging from 10 to
100 m in size (Fig. 3a and b, chosen as representatives) probably

cemented by cristobalite. Isolated grains of feldspars and/or quartz

have also been detected in some samples (Fig. 3c).
The smectite particles forming the aggregates are less than 2 m in
size, and they are characterized by at-lying or corn-ake morphologies
(Fig. 3d and e). Only in few cases the smectite appears as isolated particles (Fig. 3f).
4.5. Pharmacopoeial requirements
4.5.1. Cation exchange capacity and specic surface area
Table 5 summarizes the data on MBA, CEC and SSA. In samples from
eastern and central Iran, the highest values were found in sample ST,
with almost 2.5 times the average of the other samples in this group.
The lowest values were found in the EM sample, linked to the presence
of noticeable amounts of minerals such as illite, kaolinite or plagioclases.
In bentonite JM the interlayer cations were exchanged with Na+,
resulting in the highest values of all analyzed samples (around 3 times
the average of the other samples).
Even though sample JM requires a treatment, the obtained values
make it the best material for pharmaceutical uses in which specic
surface was relevant.

Fig. 3. Some examples of the bentonite micromorphology found in Iranian samples. a) SGC; b) JM; c) EM; d) EM; e) SGC; f) SGC.

S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

Table 5
Methylene blue adsorption (MBA), cation exchange capacity (CEC) and specic surface
area (SSA) of samples.

199

Table 7
Power ow characteristics of the studied samples (standard deviations in parentheses, n = 3): bulk (b) and tapped density (t), Carr index (CI) and Hausner ratio (HR).

Sample

MBA (g/100 g)

CEC (mEq/100 g)

SSA (m2/g)

Sample

b (g/mL)

t (g/mL)

CI (%)

H.R.

SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JMa

11
17
11
11
9
25
9
10
8
29

33
52
33
34
28
78
28
31
25
91

261
404
258
296
219
612
220
295
196
710

SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JM

1.05 (0.05)
0.55 (0.01)
1.03 (0.02)
0.64 (0.02)
0.57 (0.03)
0.81 (0.04)
0.68 (0.05)
1.02 (0.01)
0.98 (0.03)
0.99 (0.05)

2.09 (0.05)
0.77 (0.03)
1.23 (0.04)
0.83 (0.01)
0.74 (0.01)
1.03 (0.01)
0.89 (0.02)
1.29 (0.01)
1.21 (0.03)
1.30 (0.04)

49.76 (0.08)
28.57 (0.02)
16.26 (0.04)
22.89 (0.08)
21.97 (0.06)
21.36 (0.04)
23.60 (0.05)
20.93 (0.02)
19.01 (0.08)
23.85 (0.08)

1.99 (0.05)
1.40 (0.03)
1.19 (0.02)
1.30 (0.03)
1.30 (0.01)
1.27 (0.01)
1.31 (0.01)
1.26 (0.04)
1.23 (0.05)
1.31 (0.04)

JM sample is calcium montmorillonite in nature and has been saturated with Na.

4.5.2. pH
Na smectites show a pH value comprised in the 8.349.75 interval
(Table 6). On the contrary, the Ca montmorillonite (sample JM) exhibits
the lower value: 7.36. These pH values are appropriate for topical uses of
the studied materials (Viseras et al., 2006; Abdel-Motelib et al., 2011).
Skin surface pH depends on both endogenous and exogenous factors,
and the normal pH value (5.5) may raise or decrease after application
of topical products, returning to baseline in minutes (Korting et al.,
1987; Moldovan and Nanu, 2010).
4.5.3. Powder ow characteristics
The density, CI and HR results are listed in Table 7. According to the
HR values, almost all the studied powders showed acceptable ow characteristics (1.25 b HR b 1.5). The exceptions were SGA, with poor ow
(HR N 1.5) and SGC with good ow behavior (HR b 1.25). The Carr
index allowed a more detailed discrimination of ow properties of the
samples. According to the results, SGA would correspond to a practically null ow powder (IC N 40) and SGC to a good ow powder
(12 b IC b 18). Between these two extremes, the remaining samples
showed with an acceptable (18 b IC b 22) or poor ow characteristics
(23 b IC b 35). Technical modications and/or formulation with lubricants can improve the behavior of both acceptable and poor ow
powders (Viseras and Lpez-Galindo, 2000; Yang et al., 2005).
4.5.4. Swelling capacity and sedimentation volume
On the basis of sedimentation volumes, all dispersions yielded
occulated systems when dispersed (Gennaro, 1998) (Table 8). This
property is required for the formulation of suspensions with optimal
physical stability. Moreover, samples were also usable to formulate
ideal and pharmaceutically acceptable suspensions because no compact
sediment formation was observed (Martin et al., 1993).
Table 8 shows also the swelling capacity of the samples. Sediment
volumes higher than 22 mL correspond to good swelling of pharmaceutical clay suspensions (EP 7.0, 2011; USP 36NF 31, 2013). As observed,
the samples with high smectite content (12 ) show high swelling

4.5.5. Rheological properties

Fig. 4a and b show the ow curves of the clay suspensions. In these
gures, suspensions prepared with SK and SGB show the highest ow
proles, whereas sample JM presents the lowest shear stress values.
FKH and SGC show similar proles with relatively low shear stress
values. Fig. 4b shows ow curves of very similar intermediate behavior,
corresponding to samples EM, FGH, SGA, SP and ST. Most of the samples
showed thixotropy. This property is very important, allowing the use of
clay samples in semisolid health care products (Viseras et al., 2006).
Table 9 summarizes the apparent viscosities of the clay suspensions
(at 50 s 1 shear rate). The average apparent viscosities were higher
than 4 Pa s in all samples, except JM. This value was described in semisolid clay systems used in pelotherapy (Cara et al., 2000). The JM sample, with low swelling capacity, also had the lowest apparent viscosity.
5. Conclusions
Smectites can be considered as raw pharmaceutical materials once
their quality attributes have been assessed. In particular, their identity,
purity, richness and technical properties must be controlled. With
these premises, we analyzed the mineral and chemical composition of
ten Iranian bentonites. Most of the samples mainly consisted of montmorillonite, but the presence of important quantities of cristobalite in
some samples could compromise their use and would require mineral
purication treatments before use. Sample JM could be considered a
pharmaceutical grade bentonite.
As mined materials, smectites contain metal impurities that must be
controlled. In the studied samples, these are within the required limits,
except for the high amount of As in EM sample. Microbial testing of the
samples guarantees the safety of using Iranian bentonites as pharmaceutical excipients.
Regarding technical properties, the samples showed adequate
performance. In particular, the swelling capacity, sedimentation volume
Table 8
Swelling capacity and sedimentation volumes (SV) of the studied samples (standard
deviations in parentheses, n = 3).

Table 6
pH of the analyzed samples.
Samples

characteristics, whereas the JM sample, mainly composed of smectite

with interlayer space around 14 , showed a very low swelling capacity.

pH values

Sample

Swelling capacity
(mL of sediment)

SV

SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JM

34 (1.3)
22 (1.1)
36 (1.0)
36 (1.2)
32 (1.2)
36 (1.4)
36 (0.9)
26 (0.8)
34 (1.2)
4 (0.2)

0.99 (0.02)
0.97 (0.04)
0.99 (0.05)
0.98 (0.01)
0.98 (0.01)
0.98 (0.03)
0.98 (0.02)
0.99 (0.04)
0.98 (0.08)
0.96 (0.05)

(2 g/50 mL)
SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JM

8.52
8.80
9.75
8.34
8.89
8.90
8.59
9.12
9.48
7.36

200

S. Modabberi et al. / Applied Clay Science 116117 (2015) 193201

Geology of the University of Tehran for sample preparation and some

geochemical tests. The authors also express their gratitude to Dr. M.A.
Amouzgar, professor of the School of Biology of the University of Tehran
and his assistant, Ms. Mehrshad, for microbiological tests.

References

Fig. 4. a. Flow curves of suspensions prepared with SGB, SGC, SK, FKH and JM samples. b. Flow
curves of suspensions prepared with EM, FGH, SGA, SP and ST samples.

and rheological properties of their water suspensions were, in general,

adequate to their use in semisolid health care products.
As a general conclusion, two of the studied samples (JM and SGC)
showed appropriate composition, purity and technical properties to be
used in pharmaceutical applications, whereas the rest would require
purication or improvement of their properties. In particular, the samples could be used for topical dosage forms as rheological additives.
Acknowledgments
This research was partly funded by the Iran National Science Foundation (contract no. 90004849). We also acknowledge the School of
Table 9
Apparent viscosities of the sample suspensions (30% w/v) in
distilled water (standard deviations in parentheses, n 3).
Sample

Apparent viscosity
at 50 s1 (Pa s)

SGA
SGB
SGC
SK
SP
ST
FGH
FKH
EM
JM

11.04 (0.06)
14.73 (0.07)
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17.91 (0.32)
8.65 (0.10)
8.84 (0.24)
8.16 (0.19)
4.22 (0.58)
7.73 (0.08)
0.43 (0.05)

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