Hindawi

Journal of Spectroscopy
Volume 2019, Article ID 2960845, 6 pages
https://doi.org/10.1155/2019/2960845

Research Article
FT-IR Spectroscopy Applied for Identification of a Mineral Drug
Substance in Drug Products: Application to Bentonite

H. Ouhaddouch ,1 A. Cheikh ,2 M. O. B. Idrissi,1 M. Draoui,1 and M. Bouatia 1

1
Laboratory of Analytical Chemistry, Team of Formulation and Quality Control of Health Products,
Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
2
Faculty of Pharmacy, Abulcasis University, Rabat, Morocco

Correspondence should be addressed to H. Ouhaddouch; [email protected]

Received 4 December 2018; Revised 28 January 2019; Accepted 5 February 2019; Published 3 March 2019

Academic Editor: Alessandra Durazzo

Copyright © 2019 H. Ouhaddouch et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The aim of this study is to prove the effectiveness of IR spectroscopy as an identification test able to discriminate between mineral
compounds in mixtures. This work is concerned with the physical characterisation of purified bentonite, bentonite in organic
mixtures and organic excipients, and mineralized organic mixture containing bentonite using FT-IR spectroscopy. The different
spectra were compared with each other in order to determine fingerprints of bentonite represented by bands located at 3632 cm−1
and 3437 cm−1. The analysis of the spectra of the nonmineralized mixture demonstrates the presence of two bands at 1454 and
2928 cm−1, superimposed on those of the excipients and which disappear after 2 hours of mineralization at 500°C. Finally, we
notice a displacement of the stretching band of H2O to the right with increasing the proportion of the excipients.

1. Introduction applied in the field of mineral chemistry, this spectroscopic

method is the reference for identification of organic drug
Over the last decade, infrared (IR) spectroscopy had proved to substances in pharmacopeia. The IR spectroscopy is mainly
be a powerful analytical method widely applied in quality complementary to X-ray diffraction (XRD) and other
control in the field of agricultural, environment, food, and methods used to study clays.
especially pharmaceutical. It is the best technique used in the The interpretation of the different IR spectra remains
investigation and identification of clays and clay minerals, empirical and consists most often in comparing the results
especially bentonite, by a combination of spectroscopic and obtained with previously recorded reference spectra or to
spatial information [1, 2]. Using this method, selected sample put in evidence important structural parts of the mole-
areas can be analyzed with reference to the identification and cules with intense vibration bands [4–6], even if the
localization of chemical species by Fourier-transform infrared substance is in mixtures or complexes [7]. It is based
spectroscopy (FT-IR) in the transmission or attenuated total mainly on the analysis of IR spectra of isolated molecules.
reflection (ATR) mode [3]. However, since these spectra can serve as fingerprints for
On the other hand, FT-IR is an excellent technique for identification, we are interested in proving the effec-
pharmaceutical analysis which offers many advantages since it tiveness of this spectral method in the identification of a
is easy to use, sensitive, selective, green, and fast (the total mineral product that cannot be detected by HPLC in a
analysis time including making the pellets, measurement, mixture.
identification, and report generation is lower than The aim of this study is to develop a new method for
10 minutes) and helps ensure regulatory compliance through identification of the drug substance as purified bentonite in a
validation protocols. Contrary to high-performance liquid drug product, using FT-IR spectroscopy in order to apply it
chromatography (HPLC) which is less fast, requires the in several fields such as industrial pharmacy to analyze
preliminary preparation of the mobile phase, and is not mineral intestinal adsorbents [8].
2 Journal of Spectroscopy

2. Materials and Methods Table 1: Composition of the studied mixtures.

Bentonite Glucose Menthol
2.1. Preparation of Mixture. The starting material is ben- Code Mixtures
(mg) (mg) (mg)
tonite clay, which belongs to the family of crystalloids. Five
M80 Mixture 80% 80 19 1
mixtures of drug products were prepared of each pro-
M60 Mixture 60% 60 39 1
portion of bentonite (Sigma-Aldrich, analytical grade), M40 Mixture 40% 40 59 1
pure glucose monohydrate (Riedel-de Haën, analytical B Bentonite 100 — —
grade), and menthol (BASF, pharmaceutical grade) (Ta- G Glucose — 100 —
ble 1). The mixtures thus formed are triturated in a por-
celain mortar to reduce the average particle size to 1-2 μm
in order to promote the homogeneity of the samples [9]. In sample. Spectra Manager II spectroscopy software developed
effect, the size of the particles influences the amount of by JASCO ensures spectral acquisition and processing.
absorption of the sample and the intensity of the absorption The first part of this work was reserved to record the
peaks of its spectrum. The difference in particle size be- spectra of mineralized mixture MM80 for different dura-
tween the different constituents of the mixture then tions in the aim to determine the time required for the
complicates the analysis of the mixture spectra in which the complete mineralization of glucose and menthol (excipi-
coarsest compound becomes predominant [10]. ents). The second part of this work is to identify functional
The aim is to have mixtures sufficiently simple to acquire groups of nonmineralized mixture by measuring the ab-
a knowledge of the interaction spectra related to the su- sorption at specific wavelengths of bonds that vibrate in-
perposition of the absorption spectra of the different species, dependently of one another in order to confirm that the FT-
knowing that the additivity of the absorbances is an ideal IR spectroscopy is the most efficient method able to dis-
case. The mixtures thus prepared will be read after by IR criminate between different compounds of drug product.
spectroscopy.
3. Results and Discussion
2.2. Mineralization of the Mixture. The determination of the 3.1. Mineralization of the Mixture. Disappearance of func-
time required for the complete mineralization of glucose and tional groups during the process of mineralization can be
menthol (excipients) led us to prepare six samples of mixture successfully monitored by transmission FT-IR spectrometry.
80% (M80) and one sample of purified bentonite (B). Each The focus was on the band located at 2928 cm−1 corre-
100 mg sample was placed in a porcelain crucible at a tem- sponding to C-H stretching which is specific to organic
perature of 500°C in a temperature-controlled oven of the compounds: glucose and menthol. The IR spectra of the
Conacom Italia type. The crucibles of the mixture were re- mixture M80 mineralized at 500°C for 30, 60, 90, and
covered one after the other every 30 minutes for 3 hours, in 120 min (Figures 1 and 2) show a gradual decrease in the
order to be analyzed by FT-IR spectroscopy using the intensity of this band, until disappearance from the second
transmission mode. hour (crucibles 4, 5, and 6). The disappearance of this peak
testifies to a complete mineralization of the organic matter
used in the preparation of the mixture (glucose and men-
2.3. Measurement by Fourier-Transform Infrared Spectroscopy
thol). Consequently, the MM80 mixture used in our study
(FT-IR). The FT-IR spectroscopy using the transmission
represents a M80 mixture mineralized at 500°C for 2 hours.
mode is an intuitive method which does not require so-
phisticated sampling accessories. The sample can be placed
directly into the path of the infrared beam (with the help of a 3.2. Data Processing of the Infrared Spectrometry. IR spec-
sample holder), and 128 scans were collected with a reso- troscopy analysis of the different mixtures studied requires
lution of 4 cm−1 for each measurement over the spectral an understanding of the absorption bands attributable to the
range of 500–4000 cm−1. different physical and chemical properties of the material
FT-IR spectroscopy using KBr-pressed disk technique was and which are used to assist in the identification of the
conducted on a JASCO FT-IR 460 PLUS spectrometer (Pike various compounds that make up the mixture.
Technologies, Madison, USA) equipped with a pyroelectric It is well known that molecule analyzed by IR spec-
DLATGS detector. 2.5 mg of each mineralized sample and troscopy absorbs only the frequencies of IR light that
100 mg of potassium bromide (Honeywell Fluka, infrared match vibrations that cause a change in the dipole moment
grade) were weighted, ground in an agate mortar, and pressed of the molecule. Every molecule, with the exception of
for 2 minutes at 10 tones/cm2 to form a semitransparent pellet enantiomers, has a unique infrared spectrum. This is due to
which lets light to be transmitted to the detector [11, 12]. The the fact symmetrical structures and identical groups at
pellet was placed in the IR beam using the sample trans- each end of one bond will not absorb in the IR range [13].
mission holder. The samples analyzed were nonmineralized The spectrum has two regions. The fingerprint region is
glucose (G), purified bentonite (B), mineralized bentonite unique for a molecule, and the functional group region is
(MB), nonmineralized mixture 80% (M80), mineralized identical for molecules with the same functional groups
mixture 80% (MM80), nonmineralized mixture 60% (M60), [13].
and nonmineralized mixture 40% (M40). Three measure- The FT-IR spectral examination of purified bentonite
ments were carried out in the transmission mode for each revealed different bands (Table 2) comparable to those
Journal of Spectroscopy 3

2
Abs.

1
Figure 2

0
4000 3000 2000 1000 500
Wavenumber (cm–1)
30 minutes 90 minutes
60 minutes 120 minutes
Figure 1: FT-IR spectra of nonmineralized mixture 80% (M80) mineralized at 500°C for different durations.

0.17 defined by the literature [14–18]. Two bands of different

30 min intensities, located at 3632 cm−1 and 3437 cm−1, also
0.15 60 min
defined by Jeddi et al. [19], constitute the spectral sig-
90 min 120 min
nature specific to bentonite which allows its identification
in a mixture of species. These bands correspond, re-
spectively, to the vibrational modes of hydroxyl groups
0.1
and water molecules absorbed in the interstitial spaces of
Abs.

the bentonite.
According to the spectra of the mineralized bentonite
0.05 and purified bentonite obtained (Figure 3), the general
appearance is similar, but we can see a significant decrease
in the intensity of the band at 3437 and 1638 cm−1 related
to H2O absorbed on the samples, and a well-resolved band
0 at 3632 cm−1 assigned to OH− stretching vibrations of
2960 2940 2920 2900 2880 2870 structural hydroxyls remained [20]. This change of in-
Wavenumber (cm–1)
tensity means that the hydrophilicity of the bentonite
Figure 2: Spectral band characteristic of nonmineralized mixture decreased.
80% (M80) after mineralization at 500°C for 30, 60, 90, and Figure 4 shows FT-IR spectra of the mineralized ben-
120 minutes. tonite and the excipients as well as those of the mixtures M80
and MM80. The different spectra were compared with each
other in order to obtain information on the differences
between the mineralized bentonite and the mixtures M80
Table 2: IR bands characteristic of the purified bentonite spectrum. and MM80. The spectra of the mixture MM80 are com-
pletely confused with those of the mineralized bentonite.
Transmission vibrational
Strength Functional groups However, those of the mixture M80, unlike the mixture
frequency (cm−1)
MM80, have in the field ranging from 1300 to 4000 cm−1 and
3632 Medium OH stretching
in addition to the bands characteristic of the hydroxyl group
3437 Medium H2O stretching
1638 Weak H2O bending
(3632 cm−1) and water (3437, 1638 cm−1), a small band at
1042 Broad Si-O stretching 1454 cm−1 and a sharper band at 2928 cm−1. This supports
915 Broad Al-OH-Al bending the additivity of absorbances of the excipients and the
884 Medium Al-OH-Fe bending bentonite.
842 Medium Al-OH-Mg bending The FT-IR spectroscopy of the mixtures M80, M60,
795 Weak
Si-O stretching of M40, and excipients shown in Figure 5 was carried out for a
quartz and silica comparative purpose in order to obtain information about
Al-O + Si-O out-of-plane the modification of the mixture spectra while increasing the
622 Weak
vibration proportion of the excipients. The position, the shape, and
522 Broad Al-O-Si bending the intensity of the stretching band of H2O at 3437 cm−1
4 Journal of Spectroscopy

2
Abs.

1
B
MB

0
4000 3000 2000 1000 500
Wavenumber (cm–1)
Figure 3: FT-IR spectra of purified bentonite (B) and mineralized bentonite (MB).

2
Abs.

M80

1
MM80 Excipient
MB

0
4000 3000 2000 1000 500
Wavenumber (cm–1)
Figure 4: FT-IR spectra of mineralized bentonite (MB) and mineralized mixture 80% (MM80) versus those of nonmineralized mixture 80%
(M80) and excipients.

Excipient
Abs.

M40
M60
1 MM80
M80

0
4000 3000 2000 1000 500
Wavenumber (cm–1)
Figure 5: FT-IR spectra of mineralized mixture 80% (MM80), nonmineralized mixture 80% (M80), nonmineralized mixture 60% (M60),
nonmineralized mixture 40% (M40), and excipients.
Journal of Spectroscopy 5

were influenced by the addition of the excipients. Indeed, References

we notice a displacement of this band to the right with
increase in its intensity while going from the mixture M80 [1] M. L. McKelvy, T. R. Britt, B. L. Davis et al., “Infrared
to the mixture M40. The absorption bands observed at 1454 spectroscopy,” Analytical Chemistry, vol. 68, pp. 93–160, 1996.
[2] B. Stuart, Modern Infrared Spectroscopy, p. 180, John Wiley &
and 2928 cm−1 in the FT-IR spectra of the M80 mixture
Sons, New York and Chichester, UK, 1996.
increase their intensity with increasing concentration of the
[3] O. Kolomiets, U. Hoffmann, P. Geladi, and H. W. Siesler,
excipients. “Quantitative determination of pharmaceutical drug formu-
Unlike to FT-IR spectroscopy which is a simple, fast, lations by near-infrared spectroscopic imaging,” Applied
cheaper, and extremely useful for the characterisation of Spectroscopy, vol. 62, no. 11, pp. 1200–1208, 2008.
both organic products and inorganic products, the HPLC is [4] A. A. Bunaciu, H. Y. Aboul-Enein, and S. Fleschin, “Appli-
a method which represents some limitations rarely discussed cation of Fourier transform infrared spectrophotometry in
that promotes the utilisation of FT-IR spectroscopy. pharmaceutical Drugs analysis,” Applied Spectroscopy Re-
The HPLC requires a sophisticated instrumentation with views, vol. 45, no. 3, pp. 206–219, 2010.
bewildering number of modules, columns, and mobile [5] J. M. Chalmers and P. R. Griffiths, Handbook of Vibrational
phases, operating parameters render HPLC difficult for the Spectroscopy, John Wiley & Sons, London, UK, 2002.
novice, and it is relatively expensive [21]. It can also be time- [6] B. Özlem, Determination of Narcotic and Psychotropic Sub-
consuming, tedious, arduous, involve extensive chemical stances Using Infrared Spectroscopy, M.S. Thesis, Middle East
use, need regular maintenance requirements, and sometime, Technical University Ankara, 2005.
require pretreatment of samples [21, 22]. But, the main [7] E. A. Budura, D. Lupuleasa, C. Aramă, G. M. Nitulescu, and
T. Balaci, “Preparation and characterization of inclusion
drawbacks of HPLC are the lack of a high-sensitivity uni-
complexes formed between simvastatin and hydroxypropyl–
versal detector and the insufficient chromatographic effi-
β–cyclodextrin,” Farmacia, vol. 59, p. 512, 2011.
ciency to separate many complexes like the inorganic [8] GUIDELINE, “ICH Harmonized Tripartite, “Specifications:
products [22–24]. test procedures and acceptance criteria for new drug sub-
Therefore, we can confirm that the FT-IR spectroscopy, stances and new drug products: chemical substances Q6A”,”
applied to study drug product, is a very sensitive technique Current Step 4 version, Dated October 6, 1999, 2015.
that provides a relatively easy and fast way to determine an [9] G. Krishna, M. Muthukumaran, B. Krshnamoorthy, and
unknown mineral drug substance, by giving detailed A. Nishat, “A critical review on fundamental and pharma-
qualitative information on chemical composition of the ceutical analysis of FTIR spectroscopy,” International Journal
analyzed material along with a unique fingerprint that of Pharmacy, vol. 3, p. 396, 2013.
often enables confirmation of its identity [25]. This iden- [10] J. K. Crowley and N. Vergo, “Near-infrared reflectance spectra
tification and recognition of its presence in mixtures are of mixtures of kaolin-group minerals: use in clay mineral
more certain when its absorption bands are numerous and studies,” Clays and Clay Minerals, vol. 36, no. 4, pp. 310–316,
sharply defined and if there appears a distinctive region of 1988.
the spectrum. [11] J. Madejová, “FTIR techniques in clay mineral studies,” Vi-
brational Spectroscopy, vol. 31, no. 1, pp. 1–10, 2003.
[12] L. Ohannesian and A. J. Streeterhandbook, Handbook of
4. Conclusions Pharmaceutical Analysis, Marcel Dekker, New York, NY,
USA, 2002.
The present study clearly demonstrates that FT-IR spec- [13] A. E. Segneanu, I. Gozescu, A. Dabici, P. Sfirloaga, and
troscopy is an efficient method for the characterisation of the Z. Szabadai, “Organic compounds FT-IR spectroscopy,” in
purified bentonite in an organic mixture. This technique Macro To Nano Spectroscopy, InTech, Romania, 2012.
remains economical, rapid, and specific. The spectrum can [14] J. Madejová and P. Komadel, “Baseline studies of the clay
be obtained in a few minutes using the inexpensive in- minerals society source clays: infrared methods,” Clays and
struments, which can be available in many analytical lab- Clay Minerals, vol. 49, no. 5, pp. 410–432, 2001.
oratories and can be served as a fingerprint for new drugs of [15] A. Eisazadeh, K. A. Kassim, and H. Nur, “Solid-state NMR
mineral origin as an alternative to chromatographic re- and FTIR studies of lime stabilized montmorillonitic and
tention time in HPLC. lateritic clays,” Applied Clay Science, vol. 67-68, no. 5,
Indeed, the FT-IR spectroscopy can be combined with pp. 5–10, 2012.
other spectral methods such as X-ray diffraction in order to [16] Z. Hubicki, E. Zieba, G. Wojcik, and J. Ryczkowski, “FT-IR/
increase the specificity of the technique. PAS and SEM EDX studies on aluminosilicates modified by
Cs(I), Th(IV) and U(VI),” Acta Physica Polonica A, vol. 116,
no. 3, pp. 312–314, 2009.
Data Availability [17] S. İşçi, C. H. Ünlü, O. Atici, and N. Güngör, “Rheology and
structure of aqueous bentonite polyvinyl alcohol dispersions,”
The data used to support the findings of this study are in- Bulletin of Materials Science, vol. 29, no. 5, pp. 449–456, 2006.
cluded within the article. [18] A. Eisazadeh, A. K. Kassim, and H. Nur, “Physicochemical
characteristics of phosphoric acid stabilized bentonite engi-
Conflicts of Interest neering,” EJGE, vol. 15, p. 327, 2010.
[19] S. Jeddi, A. Ouassini, M. El Ouahhaby, and H. Mghafri,
The authors declare that they have no conflicts of interest “Valorisation of natural mineral substances (NMS) at ad-
regarding the publication of this article. sorption techniques: case of olive oil mill waste waters,”
6 Journal of Spectroscopy

Journal of Materials and Environmental Science, vol. 7, p. 488,

2016.
[20] P. Djomgoue and D. Njopwouo, “FT-IR spectroscopy applied
for surface clays characterization,” Journal of Surface Engi-
neered Materials and Advanced Technology, vol. 03,
pp. 275–282, 2013.
[21] M. W. Dong, “The essence of modern HPLC: advantages,
limitations, fundamentals, and opportunities,” LCGC North
America, vol. 31, p. 472, 2013.
[22] J. C. J. Bart, Additives in Polymers: Industrial Analysis and
Applications, John Wiley & Sons, Geleen, Netherlands, 2005.
[23] M. W. Dong, Modern HPLC for Practicing Scientists, Wiley,
Hoboken, NJ, USA, 2006.
[24] M. Swartz, M. Emmanuel, A. Awad, and D. Hartley, “Ad-
vances in HPLC systems technology,” Supplement to LCGC
North America, vol. 27, p. 40, 2009.
[25] R. I. Iliescu, E. Andronescu, G. Voicu, A. Ficai, and
C. I. Covaliu, “Hybrid materials based on montmorillonite
and citostatic drugs: preparation and characterization,” Ap-
plied Clay Science, vol. 52, no. 1-2, pp. 62–68, 2011.
 Nanomaterial
Nanomaterials
Journal of

Journal of
The Scientific
Photoenergy
International Journal of
Analytical Methods Journal of

Hindawi
in Chemistry
Hindawi
World Journal
Hindawi Publishing Corporation
Applied Chemistry
Hindawi Hindawi
www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.hindawi.com
www.hindawi.com Volume 2018
2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Advances in International Journal of

Physical Chemistry
Hindawi
Medicinal Chemistry
Hindawi
www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Submit your manuscripts at

www.hindawi.com

Bioinorganic Chemistry Journal of

and Applications
Hindawi
Materials
Hindawi
www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Advances in Journal of BioMed International Journal of International Journal of

Tribology
Hindawi
Chemistry
Hindawi
Research International
Hindawi
Spectroscopy
Hindawi
Electrochemistry
Hindawi
www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

International Journal of Journal of Journal of Enzyme Biochemistry

Analytical Chemistry
Hindawi
Spectroscopy
Hindawi
Nanotechnology
Hindawi
Research
Hindawi
Research International
Hindawi
www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018