CLAY-03370; No of Pages 9

Applied Clay Science xxx (2015) xxx–xxx

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Applied Clay Science

journal homepage: www.elsevier.com/locate/clay

Research paper

Characterization of Iranian bentonites to be used as

pharmaceutical materials
Soroush Modabberi a,⁎, Alireza Namayandeh a, Alberto López-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
b
Instituto Andaluz de Ciencias de la Tierra (CSIC—Universidad de Granada), Avda. de las Palmeras, 4, 18100 Armilla, Granada, Spain
c
Dpto. Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Granada, Spain
d
Dipartimento di Scienze della Terra e dell'Ambiente, Università di Pavia, Via Ferrata 1, 27100 Pavia, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Ten Iranian bentonites, sampled from the deposits of Chah-Golestan, Chah-Pirouz, Chah-Keshmir and Chah-Taleb
Received 29 November 2014 (Sarayan), Gholeh-Gelia and Kharman-Sar (Ferdows, Khorasan), Mehrejan (Khoor) and Manian (Zagros) were
Received in revised form 11 March 2015 analyzed to evaluate their potentialities as pharmaceutical products. The mineralogy, chemistry, pH, microbial
Accepted 14 March 2015
content, powder flow characteristics, swelling capacity, cation exchange capacity, specific surface area, sedimen-
Available online xxxx
tation volume, and rheological properties of all samples were determined. The bentonite located in carbonate
Keywords:
rocks (Zagros) is made up of calcium montmorillonite (97%) and quartz (3%). The rest of the bentonites are
Iranian bentonites hosted by Eocene volcanic rocks and are mainly made up of sodium montmorillonite (47%–84%) and cristobalite
Montmorillonite (up to 39%), with lesser quantities of quartz, calcite, plagioclase, zeolites and halite. Two of the samples (those
Pharmaceutical formulations located at Manian and Chah-Golestan C) showed appropriate composition, purity and technical properties to
Trace elements be used in pharmaceutical applications, whereas the rest would require purification or improvement of their
Thixotropy properties. In particular, the samples could be used for topical dosage forms as rheological additives.
Excipients © 2015 Elsevier B.V. All rights reserved.

1. Introduction Luckham and Rossi, 1999; Allo and Murray, 2004; Eisenhour and
Brown, 2009; Guven, 2009; Abdel-Motelib et al., 2011; Agha et al.,
Clay minerals are among the mostly used minerals in numerous ap- 2012). Because of these various properties, bentonites are being used
plications. The most common uses are foundry sand bonds, drilling in an increasing number of applications, especially in the pharmaceuti-
mud, ceramics, filtration, and iron ore pelletizing (Allo and Murray, cal industry (Williams et al., 2009; Abdel-Motelib et al., 2011; Carretero
2004). Since early times various types of clay minerals have been used et al., 2013) and in pleotherapy and medical applications (Summa and
in the traditional medicines of most countries. The term “bentonite” is Tateo, 1998; Cara et al., 2000; Veniale et al., 2004, 2007; Tateo and
used in the industry for clays mostly composed of smectite group min- Summa, 2007; Carretero et al., 2010, 2014; Karakaya et al., 2010;
erals (Grim and Guven, 1978). However in pharmaceutical literature, Gomes et al., 2013).
“bentonite” is used to refer to a natural, colloidal, hydrated aluminium The mineralogical and chemical compositions of bentonites depend
silicate (Viseras et al., 2006; USP 36–NF 31, 2013). The main minerals on their evolution from parent rocks. Hence, their chemical composition
of the smectite group are calcium montmorillonite, sodium montmoril- and physical properties should be determined carefully before any
lonite, saponite, nontronite, hectorite, and beidelite (Murray, 2007). The usage, especially in cosmetic and pharmaceutical purposes, and special
colloidal size and structure of smectite minerals mean that they have a precautions should be taken (López-Galindo et al., 2007), given that a
wide range of applications in industry as a result of their rheological clay mineral must comply with several chemical, physical, and toxico-
properties, absorbing capacity, plasticity, high specific surface area, logical requirements for use in pharmaceutical formulations, depending
CEC and swelling properties. Among all members of clay minerals, calci- on whether the purpose is therapeutic or cosmetic.
um and sodium montmorillonites are among the most frequently used
of all the clay minerals (Grim, 1962; Hartwell, 1965; Grim and Guven, 2. Geological setting
1978; Elzea and Murray, 1990; Harben and Bates, 1990; Konta, 1995;
Iranian bentonite deposits occur in six zones (Semnan–Toroud,
Alborz–Azerbaijan, Eastern Iran, Central Iran, Tafresh–Takab and
⁎ Corresponding author. Tel.: +98 21 61112985, +98 9122145463 (cellphone). Zagros), mostly in connection with Tertiary magmatism (Hejazi and
E-mail address: [email protected] (S. Modabberi). Ghorbani, 1994).

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

Please cite this article as: Modabberi, S., et al., Characterization of Iranian bentonites to be used as pharmaceutical materials, Appl. Clay Sci. (2015),
http://dx.doi.org/10.1016/j.clay.2015.03.013
2 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx

Fig. 1. Locations of the studied samples (red stars) on a geological map of Iran after Stocklin (1968) and Nabavi (1976). (For interpretation of the references to color in this figure legend, the
reader is referred to the web version of this article.)

Please cite this article as: Modabberi, S., et al., Characterization of Iranian bentonites to be used as pharmaceutical materials, Appl. Clay Sci. (2015),
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 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx 3

The deposits in Eastern and Central Iran are hosted by Eocene volca- glycol saturation for the identification of the swelling clay minerals
nic rocks and it has been suggested that they are of diagenetic origin, and heating at 550 °C in oriented aggregates. The analyses were car-
subsequent to the eruption and deposition of tuff and volcanic ash in a ried out at the University of Pavia using the following instrumental
shallow aqueous environment like a lagoon (Abedini et al., 2011; features: PW1800/10 Philips X-ray Diffractometer and X'Pert High
Namayandeh, 2011; Namayandeh et al., 2012). The Manian deposit is Score — v. 1.0b (Philips) software, Cu Kα radiation, graphite mono-
located in the carbonate rocks of the Zagros orogen, with no volcanic ac- chromator, automatic divergence slit, 45 kV, 35 mA, scan interval
tivity throughout its long geological history. from 2° to 65° 2θ, and a scan speed of 0.02° 2θ/s. The results from
About 70 bentonite mines and occurrences have been identified in the XRPD analyses were compared with those in the ICDD (Interna-
Iran, of which 59 mines are in operation producing about 400,000 t/y. tional Centre for Diffraction Data) database and with our own
50% of the mined bentonite is used in the oil industry for deep well dril- reference standards, to obtain a qualitative evaluation of the miner-
ling. The remaining 50% is used in the ceramics, paint and refining in- alogical composition of the samples. Semi-quantitative analyses
dustries (Namayandeh, 2011). were performed following Moore and Reynolds (1989), and the
Eight bentonite mines were studied in this research, including final contents of the different mineral phases were calculated by
Chah-Golestan (SGA, SGB, SGC samples), Chah-Pirouz (SP), Chah- combining XRD and chemical analytical data, following Torres-Ruiz
Keshmir (SK) and Chah-Taleb (ST) in Sarayan (Eastern Iran), and et al. (1994) and López-Galindo et al. (1996).
Gholeh-Gelia (FGH) and Kharman-Sar (FKH) in Ferdows, South Khor- The elemental compositions of bulk samples were analyzed using a
asan province (Eastern Iran zone); one mine (Mehrejan, EM) is locat- commercial wavelength dispersive X-ray fluorescence instrument
ed in Khoor, Central Iran and one mine (Manian, JM) is located in (BRUKER S4 Pioneer) equipped with an Rh anode X-ray tube (60 kV,
Jahrom, Zagros (Fig. 1). 150 mA); three analyzer crystals (OVO-55, LiF 200 and PET) and a
The bentonite deposits of Iran, except that of Manian, are associated flow proportional counter for light element detection and a scintillation
with stratabound-type volcanic rocks, and include thin gypsum layers counter for heavy elements in the same laboratory. Quantification was
(average thickness of 2 cm). The alteration of volcanic rocks to benton- made by the fundamental parameter method using Spectra Plus soft-
ite is irregular, and is more intense in some deposits such as Chah- ware linked to a BRUKER S4 Pioneer instrument. Five grams of each
Pirouz and Chah-Taleb, which show pervasive calcification, silicification powdered sample was mixed with 0.5 g of a binder (Hoechst wax C
and traces of Fe oxy-hydroxides. The color of the bentonite varies local- micropowder) and homogenized in an agate mortar. A small aluminium
ly, with white, green, red, and pink bentonites observed at the quarry sample holder about 4 cm in diameter was used to obtain an XRF-pellet.
face. However, because of percolation of Fe-bearing solutions, most The pellets were pressed at 90 bars for 30 s in a Nannetti hydraulic press.
quarry faces are red in color. Samples were heated to 900 °C for 1 h to determine loss on ignition
Chah-Golestan deposit is the biggest bentonite mine in Eastern Iran (LOI).
deposits, and Manian deposit is located in Oligocene–Miocene Trace elements were determined using inductively coupled plasma-
carbonate rocks, with a 0.5–1 m layer of green-colored bentonite, mass spectrometry (ICP-MS) in the AMDEL Labs Corp, Australia.
which is mined in small scale by underground mining techniques Scanning electron microscope (SEM) observations were performed
(Namayandeh, 2011). using a LEO 1430VP ZEISS system equipped with microanalysis (Centro
de Instrumentación Científica, Granada University). Samples were
3. Materials and methods graphite-coated before analysis.

Ten representative samples averaging 1 kg in weight, were collected

3.2. Microbiological tests
from the different mines. Three samples were taken from the Chah
Golestan deposit because of the variety of bentonite types observed
In order to determine the hygienic quality of the bentonites – a pre-
there. Samples were powdered to b20 μm, dried at 65 °C, and kept in
requisite for their eventual use for purposes of human health – samples
a desiccator for at least 48 h before testing.
were tested for the presence of some microorganisms (Escherichia coli,
Macroscopic observation showed all samples to be fine-grained, ho-
Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans)
mogeneous and generally light-colored: white (SP, SK, ST, FGH, SGB),
(Viseras and López-Galindo, 1999; Viseras et al., 2006; Abdel-Motelib
beige (EM, JM, FKH) or pink (SGA, SGC).
et al., 2011; EP 7.0, 2011; USP 36–NF 31, 2013). The culture and method
of preparing suspensions were adapted from Viseras et al. (2006).
3.1. Mineralogy and chemistry

The mineralogical analyses were carried out using X-ray powder 3.3. Pharmacopoeial tests
diffractometry (XRPD) on natural samples, and after the standard
treatments for the identification of the clay minerals: ethylene– 3.3.1. Methylene blue adsorption
Samples can be classified according to their ability to adsorb this dye
Table 1 and, indirectly, their ability to retain micro-organisms, following the
Mineralogical composition of the studied samples, and d(001) spacing of montmorillonite. methodology described in USP 36–NF 31 (2013).
SGA SGB SGC SK SP ST FGH FKH EM JM
Table 2
Montmorillonite 73 56 84 65 60 71 70 68 47 97 Structural formula (per half unit cell) of Iranian montmorillonites.
Illite – – – – – – – – 11 –
Kaolinite – – – – – – – – 15 – Tetrahedral Octahedral sheet Interlayer
Quartz 1 3 1 – – – 2 1 3 3 sheet
Plagioclases – – – – – 3 9 10 – IV VI
Si Al Al Mg Fe Ti K Ca Na
Cristobalite 25 25 5 34 39 26 25 11 7 –
Calcite 1 3 6 – – – – 9 5 – SGA 3.92 0.08 1.36 0.27 0.24 0.01 0.01 0.04 0.58
Clinoptilolite – 13 – – – – – 2 – – SGC 3.80 0.20 1.34 0.30 0.27 0.02 0.04 0.02 0.59
Halite – – 4 1 1 3 – – 2 – SK 3.96 0.04 1.50 0.33 0.12 0.00 0.02 0.05 0.41
Montmorillonite SP 3.98 0.02 1.44 0.28 0.16 0.02 0.03 0.07 0.45
d(001) Å (natural 12.4 12.4 12.3 12.5 12.4 12.4 12.2 12.4 12.4 15.1 ST 3.98 0.02 1.45 0.31 0.10 0.00 0.02 0.06 0.58
smectite) FGH 3.87 0.13 1.35 0.31 0.20 0.02 0.06 0.07 0.55
d(001) Å (glycol) 16.8 16.9 17 16.9 16.8 16.9 16.9 16.9 16.9 16.7 JM 3.87 0.13 1.39 0.57 0.12 0.01 0.18 0.12 0.01

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4 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx

The methylene blue adsorption test is also used to determine the Eqs. (1) and (2), respectively, and the calculated values were used to
cation exchange capacity (CEC) and specific surface area (SSA) of clays quantify powder flow (Wells and Aulton, 2007; Rebelo et al., 2011).
in many industrial applications (ASTM, 2003). The blue halo method
was carried out on all samples to calculate these parameters (Kahr ! "
ρt −ρb
and Madsen, 1995; Viseras and López-Galindo, 1999; ASTM, 2003; CI ¼ 100 ð1Þ
ρt
Yukselen and Kaya, 2008; Abayazeed and El-Hinnawi, 2011).
All bentonites have been saturated in sodium. So, 2, 4 and 6 g of so-
dium carbonate were added to clay suspensions and methylene blue ad- ρt
HR ¼ ð2Þ
sorption was measured after 24 h repose. ρb

3.3.2. pH measurement
According to pharmacopoeial specifications for bentonite (USP 36– 3.3.4. Swelling capacity
NF 31, 2013), the pH values of clay water suspensions (2 g/50 mL) Swelling capacity of the samples was determined by measuring the
were measured after 2 min of continuous stirring. sediment volumes obtained after 2 h of repose from dispersions pre-
pared by slowly pouring (20 mg every 2 min) 2 g of powder sample in
3.3.3. Powder flow characteristics 100 mL of distilled water.
As an indirect method to address the flow characterization, the phar-
macopoeias commonly propose the measurement of bulk density (EP 3.3.5. Sedimentation volume
7.0, 2011; USP 36–NF 31, 2013). Bulk density (ρb) was measured by Sedimentation volumes were measured according to EP 7.0 (2011).
pouring samples slowly into a 250 mL calibrated measuring cylinder Briefly, 100 mL of clay suspensions (3% w/v) in distilled water was pre-
through a funnel at a fixed height above the cylinder. The tapped densi- pared by using a Silverson L5M stirrer (SILVERSON®) at 5000 rpm for
ty (ρt) was determined after 1250 taps using a pharmacopoeial tapping 20 min and then stored undisturbed at room temperature for 24 h in
density tester (Pharma test, model PT-TD200, Germany). Three repli- stoppered testing tubes. The final volumes were then recorded and
cates were carried out for each measurement and results were the corresponding sediment volumes (Sv) calculated as the ratio be-
averaged. The Carr index (CI) (Carr, 1965) and Hausner ratio (HR) tween the sediment's final volume in mL (V24) and the original volume
(Hausner, 1967) were calculated from bulk and tapped density, using (in mL) of the sample dispersions before settling (V0).

Table 3
Chemical composition of the studied samples.

SGA SGB SGC SK SP ST FGH FKH EM JM

Major elements (%)

SiO2 63.81 65.09 48.14 68.22 70.36 60.44 65.15 51.26 52.01 52.19
Al2O3 11.76 12.10 15.56 11.27 9.75 10.78 12.48 13.81 17.56 16.42
Fe2O3 3.10 1.84 4.09 1.38 1.68 1.20 2.55 4.77 3.55 2.00
MgO 1.75 2.08 2.29 1.90 1.46 1.82 1.98 3.01 1.68 4.85
CaO 0.92 2.61 3.58 0.37 0.48 0.64 0.60 6.07 3.45 1.47
Na2O 2.90 1.95 6.06 2.36 2.86 4.60 2.71 2.83 4.02 0.06
K2O 0.09 0.41 0.33 0.12 0.16 0.13 0.46 0.92 1.89 1.82
TiO2 0.19 0.29 0.34 0.01 0.16 0.01 0.29 0.86 0.82 0.19
P2O5 0.02 0.03 0.04 0.03 0.02 0.02 0.04 0.26 0.21 0.04
MnO 0.01 0.03 0.02 0.01 0.01 0.02 0.01 0.04 0.03 0.00
Cl 0.85 0.30 2.11 0.78 0.83 1.86 0.83 0.10 1.20 0.00
LOI 14.60 13.10 17.80 13.50 11.80 18.50 12.80 15.70 13.60 20.50
Total 99.99 99.81 100.35 99.95 99.57 100.02 99.89 99.63 100.01 99.53
Trace elements (ppm) Acceptable limit (ppm) Normative
As 3.9 7.5 3.4 3.9 7.4 3.5 1.8 3.5 18.0 6.3 ≤8 EP, USP
Pb a 4.4 11.9 4.7 13.7 21.4 40.3 18.7 13.3 24.0 6.7 ≤50
Hg 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.06 0.05 0.05 1 NHPD
Mo 0.4 0.3 0.4 0.1 0.4 0.5 0.9 1.2 1.3 0.5 18 ICH b
Co 3.2 3.5 7.2 0.7 0.4 3.9 4.8 15.2 9.0 3.8 5
Tl b0.1 b0.1 0.1 0.1 b0.1 b0.1 0.1 0.3 0.6 0.2 0.8
Ba 791 578 19 258 744 388 320 469 253 490 1300
Cr 2.0 7.0 2.0 2.0 2.0 2.0 10.0 44.0 12.0 16.0 1100
Cu 12 8 9 5 2 6 5 24 27 10 130
Ni 6 5 7 b2 b2 b2 8 41 13 124 60
Li b0.5 b0.5 b 0.5 b0.5 b0.5 b0.5 b0.5 b0.5 b0.5 b0.5 78
Sn 4.5 3.4 4.4 6.7 3.6 7.7 4.0 2.1 1.7 2.4 640
V 8 23 14 77 7 2 20 164 73 123 12
Zn 76 54 102 58 188 80 61 68 79 26 Low inherent toxicity
Be 1.9 2.8 2.6 4.5 2.3 6.4 2.1 1.6 2.3 0.8 Not safety concerns according to
Cs 5.8 11.8 2.7 4.8 3.4 4.3 7.6 8.3 15.2 30.3 referred normatives
Sc 6.0 8.0 10.0 3.0 7.0 4.0 6.0 11.0 8.0 5.0
Sr 146 231 94 57 100 44 120 116 234 254
Th 23 21 22 10 21 13 20 11 7 18
U 4.0 6.4 5.3 1.3 2.3 1.9 4.7 2.0 2.4 0.9
Zr 194 153 333 70 152 79 185 206 161 113
a
“Heavy metals” assay in European Pharmacopoeia match to Pb determination (EP 7.0, 2011).
b
Oral limits in drug products, drug substances and excipients, accordingly to Table A.2.2 of the Q3D guide.

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 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx 5

3.3.6. Rheological properties 7.0, 2011; USP 36–NF 31, 2013; Sánchez-Espejo et al., 2014a). In the re-
Clay/distilled water suspensions (33% w/v) were prepared by using maining samples, mineral impurities, particularly crystalline silica such
a Silverson L5M stirrer (SILVERSON®) at 5000 rpm for 20 min. Each as quartz and cristobalite, must be removed from the bentonites before
clay suspension was subjected to a complete rheological characteriza- eventual pharmaceutical applications, in order to prevent carcinogenic
tion by means of a Haake Rotovisco R1 (Haake instruments, Ltd, and other effects. The amounts of such compounds should be controlled
Germany), equipped with a plate–plate combination (P20 Ti L S) as a and their use avoided as far as possible in the pharmaceutical industry
measuring system. All measurements were carried out at 25.0 ± (IARC, 1997, 2012), even though the association of quartz with clay min-
0.1 °C, after a rest time of 3 min. Steady-shear flow tests were performed erals inhibits most adverse effects (Schins et al., 2002; Creutzenberg
over the range of shear rates from 1.0 to 100 s−1 (upwards). Downward et al., 2008).
curves (100 to 1.0 s−1) were also determined to evaluate the existence Table 2 (half unit cell) tentatively includes the structural formulae of
of thixotropy. Tests were carried out in automatic mode to ensure that dioctahedral smectites in more pure samples, as deduced from chemical
steady state at each shear rate was reached. The tests were done at analysis once the contributions of Si from quartz and cristobalite, and Ca
least in triplicate. from calcite and Na from halite have been eliminated. The results of the
formulae suggest that montmorillonite composition prevails over
4. Results and discussion 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 Data on the major and trace element contents are included in
peak around 12.4 Å, (060) reflection at 1.50 Å) (b84%), and cristobalite Table 3. Although according to the European and USA pharmacopoeias
(b39%). Calcite (1–9%) is present in Chah-Golestan and Kharman-Sar (EP 7.0., 2011; USP 36–NF 31, 2013), special attention must be paid to
deposits, plagioclases (3–9%) were detected in Ferdows deposits, and the Pb and As contents, we also took into consideration the acceptable
quartz, halite and zeolites were also found in some of these deposits, limits of other elements proposed for clays recommended for topical
normally in very low quantities (Table 1). The only exception was sam- products by the Natural Health Product Directorate (NHPD, 2013) and
ple SGB, containing 13% clinoptilolite. those included in the “Guideline for elemental impurities” in drug prod-
The sample from central Iran (EM) showed a varied clay association, ucts, recently issued by the International Conference of Harmonization
including sodium smectite (47%), kaolinite (15%) and illite (11%). Pla- (ICH, 2013) (resumed in Sánchez-Espejo et al., 2014b).
gioclases, cristobalite, calcite, quartz and halite were also present. The maximum permissible lead content in bentonite is considered to
The Zagros sample (JM) was a practically pure calcic dioctahedral be 50 ppm, and that of arsenic 8 ppm. All samples fulfill the pharmaco-
smectite, with only 3% quartz. It was the only smectite showing a dif- poeial requirements for Pb, and sample EM exceeds the permissible
fraction peak at 14.2 Å. amount of As. The content of the rest of trace elements is within the
Only samples JM and SGC fulfill the pharmaceutical requirements to- acceptable limits.
gether with mineralogical composition (López-Galindo et al., 2007; EP 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
López-Galindo, 1999; Tateo et al., 2001, 2006; Mascolo et al., 2004;
Viseras et al., 2006; Sánchez-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 influence of possible routes of administration
in the bioavailability of a particular impurity to provide route specific
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 beneficial 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).

Sample Total Escherichia Staphylococcus Pseudomonas Total Candida

aerobic coli aureus aeruginosa spores albicans
microbial

SGA A A A A A A
SGB A A A A A A
SGC 100 A A A A 1
SK 100 A A A A A
SP 500 A A A A A
ST 500 A A A A A
Fig. 2. Compositional range of selected trace elements in the studied samples (boxes), and
FGH 100 A A A A A
comparison between the average of Iranian bentonites and average of published data for
FKH 100 A A A A A
health product bentonites.
EM 3000 A A A A A
Data from Mascolo et al. (1999), Viseras and López-Galindo (1999), Viseras et al. (2006),
JM 200 A A A A A
Sánchez-Espejo et al. (2014b).

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6 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx

4.3. Microbial analysis cemented by cristobalite. Isolated grains of feldspars and/or quartz
have also been detected in some samples (Fig. 3c).
The microbial study revealed that all samples were free from patho- The smectite particles forming the aggregates are less than 2 μm in
genic bacteria (Table 4), and the total amount of microorganisms was size, and they are characterized by flat-lying or corn-flake morphologies
consistent with the pharmaceutical requirement (EP 7.0, 2011). The (Fig. 3d and e). Only in few cases the smectite appears as isolated parti-
limit for total aerobic microbial count is 103 CFU/g in “non-sterile sub- cles (Fig. 3f).
stances for pharmaceutical use”, whereas for “non-sterile oral dosage
forms containing raw materials of natural (animal, vegetal or mineral) 4.5. Pharmacopoeial requirements
origin” it increases to 104 CFU/g, reaching 105 CFU/g in some “herbal
medicinal products”. Similarly, the limit for combined yeasts/molds is 4.5.1. Cation exchange capacity and specific surface area
in the range 102–104 CFU/g, depending on the nature of the starting ma- Table 5 summarizes the data on MBA, CEC and SSA. In samples from
terial and the manufacturing process. Sterilization is recommended for eastern and central Iran, the highest values were found in sample ST,
sample EM, which showed relatively high total aerobic bacteria when with almost 2.5 times the average of the other samples in this group.
compared with the other samples (3000 UFC/g), and also for the SGC The lowest values were found in the EM sample, linked to the presence
sample, which was the only one contaminated with C. albicans. of noticeable amounts of minerals such as illite, kaolinite or plagioclases.
In bentonite JM the interlayer cations were exchanged with Na+,
4.4. Morphology and texture resulting in the highest values of all analyzed samples (around 3 times
the average of the other samples).
SEM micrographs show that all samples are characterized by the Even though sample JM requires a treatment, the obtained values
presence of pseudo-spherical smectite aggregates ranging from 10 to make it the best material for pharmaceutical uses in which specific
100 μm in size (Fig. 3a and b, chosen as representatives) probably 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.

Please cite this article as: Modabberi, S., et al., Characterization of Iranian bentonites to be used as pharmaceutical materials, Appl. Clay Sci. (2015),
http://dx.doi.org/10.1016/j.clay.2015.03.013
 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx 7

Table 5 Table 7
Methylene blue adsorption (MBA), cation exchange capacity (CEC) and specific surface Power flow characteristics of the studied samples (standard deviations in parenthe-
area (SSA) of samples. ses, n = 3): bulk (ρb) and tapped density (ρt), Carr index (CI) and Hausner ratio (HR).

Sample MBA (g/100 g) CEC (mEq/100 g) SSA (m2/g) Sample ρb (g/mL) ρt (g/mL) CI (%) H.R.

SGA 11 33 261 SGA 1.05 (0.05) 2.09 (0.05) 49.76 (0.08) 1.99 (0.05)
SGB 17 52 404 SGB 0.55 (0.01) 0.77 (0.03) 28.57 (0.02) 1.40 (0.03)
SGC 11 33 258 SGC 1.03 (0.02) 1.23 (0.04) 16.26 (0.04) 1.19 (0.02)
SK 11 34 296 SK 0.64 (0.02) 0.83 (0.01) 22.89 (0.08) 1.30 (0.03)
SP 9 28 219 SP 0.57 (0.03) 0.74 (0.01) 21.97 (0.06) 1.30 (0.01)
ST 25 78 612 ST 0.81 (0.04) 1.03 (0.01) 21.36 (0.04) 1.27 (0.01)
FGH 9 28 220 FGH 0.68 (0.05) 0.89 (0.02) 23.60 (0.05) 1.31 (0.01)
FKH 10 31 295 FKH 1.02 (0.01) 1.29 (0.01) 20.93 (0.02) 1.26 (0.04)
EM 8 25 196 EM 0.98 (0.03) 1.21 (0.03) 19.01 (0.08) 1.23 (0.05)
JMa 29 91 710 JM 0.99 (0.05) 1.30 (0.04) 23.85 (0.08) 1.31 (0.04)
a
JM sample is calcium montmorillonite in nature and has been saturated with Na.

4.5.2. pH characteristics, whereas the JM sample, mainly composed of smectite

Na smectites show a pH value comprised in the 8.34–9.75 interval with interlayer space around 14 Å, showed a very low swelling capacity.
(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 4.5.5. Rheological properties
the studied materials (Viseras et al., 2006; Abdel-Motelib et al., 2011). Fig. 4a and b show the flow curves of the clay suspensions. In these
Skin surface pH depends on both endogenous and exogenous factors, figures, suspensions prepared with SK and SGB show the highest flow
and the normal pH value (5.5) may raise or decrease after application profiles, whereas sample JM presents the lowest shear stress values.
of topical products, returning to baseline in minutes (Korting et al., FKH and SGC show similar profiles with relatively low shear stress
1987; Moldovan and Nanu, 2010). values. Fig. 4b shows flow 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
4.5.3. Powder flow characteristics
clay samples in semisolid health care products (Viseras et al., 2006).
The density, CI and HR results are listed in Table 7. According to the
Table 9 summarizes the apparent viscosities of the clay suspensions
HR values, almost all the studied powders showed acceptable flow char-
(at 50 s− 1 shear rate). The average apparent viscosities were higher
acteristics (1.25 b HR b 1.5). The exceptions were SGA, with poor flow
than 4 Pa s in all samples, except JM. This value was described in semi-
(HR N 1.5) and SGC with good flow behavior (HR b 1.25). The Carr
solid clay systems used in pelotherapy (Cara et al., 2000). The JM sam-
index allowed a more detailed discrimination of flow properties of the
ple, with low swelling capacity, also had the lowest apparent viscosity.
samples. According to the results, SGA would correspond to a “practical-
ly null” flow powder (IC N 40) and SGC to a “good” flow powder
5. Conclusions
(12 b IC b 18). Between these two extremes, the remaining samples
showed with an acceptable (18 b IC b 22) or poor flow characteristics
Smectites can be considered as raw pharmaceutical materials once
(23 b IC b 35). Technical modifications and/or formulation with lubri-
their quality attributes have been assessed. In particular, their identity,
cants can improve the behavior of both acceptable and poor flow
purity, richness and technical properties must be controlled. With
powders (Viseras and López-Galindo, 2000; Yang et al., 2005).
these premises, we analyzed the mineral and chemical composition of
ten Iranian bentonites. Most of the samples mainly consisted of mont-
4.5.4. Swelling capacity and sedimentation volume morillonite, but the presence of important quantities of cristobalite in
On the basis of sedimentation volumes, all dispersions yielded some samples could compromise their use and would require mineral
flocculated systems when dispersed (Gennaro, 1998) (Table 8). This purification treatments before use. Sample JM could be considered a
property is required for the formulation of suspensions with optimal “pharmaceutical grade bentonite”.
physical stability. Moreover, samples were also usable to formulate As mined materials, smectites contain metal impurities that must be
ideal and pharmaceutically acceptable suspensions because no compact controlled. In the studied samples, these are within the required limits,
sediment formation was observed (Martin et al., 1993). except for the high amount of As in EM sample. Microbial testing of the
Table 8 shows also the swelling capacity of the samples. Sediment samples guarantees the safety of using Iranian bentonites as pharma-
volumes higher than 22 mL correspond to good swelling of pharmaceu- ceutical excipients.
tical clay suspensions (EP 7.0, 2011; USP 36–NF 31, 2013). As observed, Regarding technical properties, the samples showed adequate
the samples with high smectite content (12 Å) show high swelling performance. In particular, the swelling capacity, sedimentation volume

Table 8
Table 6
Swelling capacity and sedimentation volumes (SV) of the studied samples (standard
pH of the analyzed samples.
deviations in parentheses, n = 3).
Samples pH values
Sample Swelling capacity SV
(2 g/50 mL) (mL of sediment)

SGA 8.52 SGA 34 (1.3) 0.99 (0.02)

SGB 8.80 SGB 22 (1.1) 0.97 (0.04)
SGC 9.75 SGC 36 (1.0) 0.99 (0.05)
SK 8.34 SK 36 (1.2) 0.98 (0.01)
SP 8.89 SP 32 (1.2) 0.98 (0.01)
ST 8.90 ST 36 (1.4) 0.98 (0.03)
FGH 8.59 FGH 36 (0.9) 0.98 (0.02)
FKH 9.12 FKH 26 (0.8) 0.99 (0.04)
EM 9.48 EM 34 (1.2) 0.98 (0.08)
JM 7.36 JM 4 (0.2) 0.96 (0.05)

Please cite this article as: Modabberi, S., et al., Characterization of Iranian bentonites to be used as pharmaceutical materials, Appl. Clay Sci. (2015),
http://dx.doi.org/10.1016/j.clay.2015.03.013
8 S. Modabberi et al. / Applied Clay Science xxx (2015) xxx–xxx

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.

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