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Vibrational Spectroscopy xxx (2012) xxxxxx
Vibrational Spectroscopy
journal homepage: www.elsevier.com/locate/vibspec
a r t i c l e
i n f o
Article history:
Received 31 October 2011
Received in revised form 10 April 2012
Accepted 2 May 2012
Available online xxx
Keywords:
Curcumin
Cyclodextrin
Freeze dried complex
Water soluble curcumin
a b s t r a c t
Many recent reports on curcumin, a polyphenol from Curcuma longa, provide mounting evidence on
the pharmacological activity of this natural product. However, the pharmaceutical use of this molecule is
hampered due to its poor solubility in the aqueous media. Inclusion complex formation with cyclodextrins
has been reported as a means to enhance its aqueous solubility. Most of these studies provide infrared (IR)
spectroscopic data as an evidence to support inclusion complex formation. However, characterization of
the solid inclusion complexes using IR spectroscopy is hindered due to interfering vibrations of cyclodextrin. In this study, fully water soluble complexes of curcumin with three hydroxypropyl derivatives of
cyclodextrins were isolated and characterized. Decrease in the intensity of aromatic ring vibrations and
shift in peak position from 1626 cm1 observed in Raman spectrum provided fresh insights into the type
of interactions occurring in the water soluble complex. A new structure for the inclusion complex has
been proposed. From the results it was demonstrated that Raman spectroscopy would provide clearer
and better evidence of inclusion complex formation.
2012 Elsevier B.V. All rights reserved.
1. Introduction
Turmeric, derived from the rhizome of Curcuma longa has been
used by the people of Indian subcontinent for centuries with no
known side effects, not only as a component of food but also to
treat a wide variety of ailments [1]. Curcumin is the phytochemical that gives yellow color to turmeric. Extensive research within
the last half century has proven that most of these activities, once
associated with turmeric, are due to curcumin [2]. Curcumin is
reported to have a number of pharmacological activities including
antioxidant, HIV antiproteases activity, anti-inammatory, analgesic, anticancer, etc. [3]. Of late, its potent antiamyloidogenic
effects in treating Alzheimers disease have ignited widespread
research interest on this drug [4]. Pre-clinical and clinical trials have
revealed that curcumin is safe even up to a dose level of 8.0 g/kg and
this makes it all the more important [5]. But the pharmaceutical use
of this pharmacologically potential molecule is restricted due to its
poor aqueous solubility, resulting in reduced bioavailability [6].
One way to increase its aqueous solubility is to form inclusion complexes, i.e., to encapsulate curcumin as a guest within the
internal cavity of a water soluble host [7]. Cyclodextrins (CDs) are
cyclic oligomers of glucose that can form water-soluble inclusion
Corresponding author at: Sree Chitra Tirunal Institute for Medical Sciences and
Technology, BMT Wing, Satelmond Palace Campus, Poojapura, Thiruvananthapuram
695012, Kerala, India. Tel.: +91 471 2520225; fax: +91 471 2341814.
E-mail address: rjoseph1965@rediffmail.com (R. Joseph).
0924-2031/$ see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.vibspec.2012.05.002
Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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P.R.K. Mohan et al. / Vibrational Spectroscopy xxx (2012) xxxxxx
Fig. 2. FTIR spectra of cyclodextrins. (a) HPCD, (b) HPCD and (c) HPCD.
Fig. 3. FTIR spectra of: (a) curcumin, (b) physical mixture (curcumin + HPCD),
(c) freeze dried complex (curcumin + HPCD) and (d) HPCD. [*] Indicates that
peaks due to (C Cring ) and mixed (C C), (C O) are masked due to the OH peaks
of cyclodextrin.
Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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Table 1
IR peak assignments of curcumin [26], HPCD, physical mixture (PM) and freeze dried complex (FDC).
Curcumin [cm1 ]
HPCD [cm1 ]
PM [cm1 ]
FDC [cm1 ]
3360
3360
3360
2929
1658
2928
2929
1658
3508
3293
2972
2945
1626
1601
1508
1429
1372
1272
1530
1458
1367
1626
1601
1510
1429
1516
1456
1367
1155
1367
1280
1155
1082
1032
1082
1031
1082
1032
944
851
753
711
948
852
753
711
950
851
753
711
1155
1150
1023
959
852
713
Peak assignment
OH stretching of phenol group, intra-molecular H bond
OH stretching
CH stretching, intermolecular H bond stretching
Asymmetric CH stretch of CH3
CH stretch of OCH3
Asymmetric CH stretching of CH2
HOH of water of crystallization, C C stretching
C O, Cring C C stretching
Aromatic C C stretching
C O stretching, CCC, CC O in plane bending
In plane bending of aromatic (CCC, CCH), enolic (COH), CH in plane
bending due to CH2
In plane bending of CH3
In plane bending of CH, enolic COH, skeletal CCC
CH in plane bending of C CH, aromatic C O stretching
CH overtone stretching, C O C stretching
In plane bending of aromatic CCH, skeletal CCH
C O, C C stretching, in plane bending of OCH
C O, C C, CCO, C O C stretching of glucose units
C O C stretching, out of plane bending of CH3 , in plane bending of
aromatic CCH
C O stretching, in plane bending of CCH
CH out of plane bending of aromatic CCH and skeletal CCH
Skeletal C C stretching, CH out of plane bending
In plane bending of skeletal CCH and aromatic CCH, C C stretching
Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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Fig. 5. Raman spectra of: (a) curcumin, (b) freeze dried complex of curcumin with
HPCD, (c) physical mixture of curcumin with HPCD, and (d) HPCD.
Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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by Sanphui et al. [31], their decrease in peak intensity was associated with a peak shift of about 9 cm1 . In the present case little
shift in peak position was observed and we can expect a different
type of interaction. It is likely that when the complex is formed the
benzene ring at one end of the curcumin will move into the cavity
of cyclodextrin where the enolic OH of curcumin form OH O bond
with the hydroxyl group of the cyclodextrin. This is depicted as a
cartoon in Scheme 1.
The cyclodextrin cage may restrict the aromatic vibrations in
Raman spectra leading to decreased peak intensity. The intensities
of the peak at 1601 cm1 (I1601 ) of curcumin and complexes, shown
Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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Table 2
Raman intensity values and curcumin content in the freeze dried complexes.
Sample details
Absorption band
position A
Raman
intensity IA
Absorption band
position B
Raman
intensity IB
IA /IB
Curcumin content
in the complex/%
Curcumin
HPCD:Curcumin (2:1) complex
HPCD:Curcumin (2:1) complex
HPCD:Curcumin (2:1) complex
1626
1635
1635
1635
3.747
0.022
0.021
0.081
1601
1603
1604
1601
6.304
0.022
0.018
0.072
0.59
1.00
1.17
1.13
0.47
0.30
2.39
Fig. 8. XRD spectra of: (a) HPCD, (b) freeze dried complex of curcumin with HPCD
and (c) curcumin.
amorphous, it did not show any melting endotherm. Physical mixture shows peaks corresponding to the melting of curcumin and
loss of water from HPCD (Fig. 9d). However, shift in peak positions are observed in this case and the melting peak is not very
sharp. It may be noted that the curcumin content in the physical
mixture was only 10 wt.%. The dilution effect by HPCD contributed
to the sharp decrease in intensity of the melting peak and its shift
towards higher temperatures. Thermogram of freeze dried complex
appears exactly like that of HPCD. The total absence of melting
endotherm of curcumin indicates that changes occurred in the
molecular level prevented crystallization of curcumin molecule.
Fig. 9. DSC analysis of: (a) curcumin, (b) HPCD, (c) freeze dried complex of curcumin with HPCD, and (d) physical mixture of curcumin with HPCD.
Authors wish to acknowledge Dr. V.K. Krishnan for the provision of spectroscopy data. They also thank the Director, SCTIMST,
Trivandrum for the facilities extended and the kind permission to
publish this work.
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FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002
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Please cite this article in press as: P.R.K. Mohan, et al., Water soluble complexes of curcumin with cyclodextrins: Characterization by
FT-Raman spectroscopy, Vib. Spectrosc. (2012), http://dx.doi.org/10.1016/j.vibspec.2012.05.002