Thermal behaviour of a modified encapsulation agent: Heptakis-6-iodo-6-deoxy-beta-cyclodextrin

Article abstract of DOI:10.1007/s10973-014-3727-1

Thermal behaviour of heptakis-6-iodo-6-deoxy-beta-cyclodextrin (HIDBCD) under inert and oxidative conditions was investigated by TG/DTG/DTA, FTIR, and using the hyphenate technique TG-FTIR. Due to the fact that thermal behaviour of HIDBCD was not studied before, we set our goal in the investigation of thermal degradation process in a dynamic air atmosphere vs. nitrogen atmosphere at a heating rate of 10 °C min^-1, up to 500 °C, respectively, 600 °C. It was found that the degradation process in air occurs in a single step, with a total mass loss of 99.9 %. The results of TG/DTG/DTA-FTIR indicated that the thermal behaviour of this cyclodextrin can be divided into three stages and more information was provided about the reaction sequences and the relevant products of reaction.

Full text of DOI:10.1007/s10973-014-3727-1

J Therm Anal Calorim
DOI 10.1007/s10973-014-3727-1
Thermal behaviour of a modified encapsulation agent
Heptakis-6-iodo-6-deoxy-beta-cyclodextrin
Adriana Fulias¸
Vasile Bercean
•
Gabriela Vlase
•
Codru t¸ a S¸ oica
•
•
Titus Vlase Ionu t¸ Lede t¸ i
•
Received: 1 November 2013 / Accepted: 23 February 2014
Ó Akad e´ miai Kiad o´ , Budapest, Hungary 2014
Abstract Thermal behaviour of heptakis-6-iodo-6-deoxy-
beta-cyclodextrin (HIDBCD) under inert and oxidative
conditions was investigated by TG/DTG/DTA, FTIR, and
using the hyphenate technique TG–FTIR. Due to the fact that
thermal behaviour of HIDBCD was not studied before, we
set our goal in the investigation of thermal degradation
process in a dynamic air atmosphere vs. nitrogen atmosphere
Introduction
Beta-cyclodextrin (BCD) is considered a ‘key molecule’ in
the field of supramolecular chemistry. Beyond the limit of
supramolecular chemistry, cyclodextrins are nowadays used
in pharmaceutical field as excipients [1] or complexation
agent in order to increase solubility of poor-soluble drugs [2].
Modified BCD is used in preclinical and clinical experi-
mental treatments for Niemann–Pick type C disease [3].
According to their toroid molecular structure and dis-
position of functional groups, cyclodextrins are less
hydrophilic inside than outside, so they can form inclusion
complexes with hydrophobic compounds enhancing their
bioavailability [4]. Combined with their insignificant
cytotoxicity, cyclodextrins are considered very appropriate
to be used as vehicles for nano-delivery systems [5].
Recent studies have even revealed that exposing cells or
model membranes to BCD results in removal of cellular
cholesterol, and a molecular mechanism of cyclodextrin
mediated cholesterol extraction was proposed [6].
-
1
at a heating rate of 10 °C min , up to 500 °C, respectively,
00 °C. It was found that the degradation process in air
6
occurs in a single step, with a total mass loss of 99.9 %. The
results of TG/DTG/DTA–FTIR indicated that the thermal
behaviour of this cyclodextrin can be divided into three
stages and more information was provided about the reaction
sequences and the relevant products of reaction.
Keywords Modified cyclodextrin ꢀ Thermal behavior ꢀ
EGA study ꢀ Encapsulation agent ꢀ Iodine
A. Fulia s¸ ꢀ C. S¸ oica ꢀ I. Lede ¸t i (&)
Faculty of Pharmacy, University of Medicine and Pharmacy
In the domain of food and drinks, cyclodextrins are used
in the stabilization of volatile or unstable compounds, as
well for the decreasing or elimination of unwanted tastes
and odours [7]. BCD inclusion complexes with food col-
ourants such as carotenoids have been shown to produce an
intensification of colour, increase water solubility, and
improve light stability [8].
‘‘Victor Babe s¸ ’’, Eftimie Murgu Square 2, 300041 Timisoara,
Romania
e-mail: ionut.ledeti@umft.ro
G. Vlase ꢀ T. Vlase
Research Centre for Thermal Analysis in Environmental
Problems, West University of Timisoara, Pestalozzi Street 16,
3
00115 Timisoara, Romania
Functionalization of naturally occurring cyclodextrins is
the main route in obtaining new modified encapsulation
agents, which can dramatically change their binding abil-
ities depending on the pH value of the medium [9].
Heptakis-6-iodo-6-deoxy-beta-cyclodextrin (HIDBCD)
is a semi-synthetic derivative (see Fig. 1) currently used as
a precursor in the synthesis of functionalised BCD that
could act as inhibitors for Anthrax toxins [10]. HIDBCD is
V. Bercean
Faculty of Industrial Chemistry and Environmental Engineering,
Politehnica University Timi s¸ oara, 6 Carol Telbisz,
3
00001 Timisoara, Romania
T. Vlase
SCIENT – Research Center for Instrumental Analysis
(
0
S.C. CROMATEC_PLUS S.R.L.), 18 Sos.Cotroceni,
60114 Bucharest 6, Romania
123

A. Fulia s¸ et al.
I
TG/DTA measurements were performed on a Perkin-
Elmer DIAMOND instrument. The experiments were car-
ried out using about 7 mg of sample which was weighted
into an open aluminium crucible. The furnace temperature
was programmed to rise under non-isothermal conditions
from ambient temperature to 500 °C linearly at a heating
O
I
O
O
I
O
HO
OH
OH
HO
-
1
HO
O
O
rate of 10 °C min . The experiments were completed in
-1
an air atmosphere at a flow rate of 100 mL min and
HO
nitrogen gas of high purity (C99.999 %) with a flow rate of
OH
-
50 mL min .
1
O
O
HO
The FTIR spectra of both pure HIDBCD and of the
remaining char after heated were carried out using a Perkin
Elmer SPECTRUM 100 device. The data was collected in
I
I
OH
O
HO
O
-1
the range of 4,000–600 cm on an UATR device, with 16
-1
acquisitions for each spectrum at a resolution of 4 cm .
HO
O
O
OH
OH
The evolved gas analysis (EGA) was carried out by a
coupled TG/FTIR technique, using a Perkin Elmer SPEC-
TRUM 100 device with an IR gas chamber connected by a
transfer line to the exit of the DIAMOND furnace which is a
HO
O
O
I
I
1
2
-m-long stainless steel tube with an internal diameter of
mm. For TG–FTIR measurements, about 10 mg sample
Fig. 1 Molecular structure of heptakis-6-iodo-6-deoxy-beta-cyclo-
dextrin (HIDBCD)
was weighted into an open aluminium crucible. In order to
assure a sufficient concentration of evolved gas mixture so
-
1
now considered an important building-block in the syn-
thesis of new modified cyclodextrins by nucleophilic sub-
stitution of iodide with different moieties [11].
FTIR spectra can be recorded, a heating rate of 20 °C min-
1
wasused, withasyntheticair/nitrogenflowof100 mL min .
Nitrogen gas of high purity (C99.999 %) was used as carried
gas. The FTIR spectra have been identified based on the FTIR
reference spectra available in the Sadtler Gas Vapor Library.
Thermal analysis is among the frequently used tech-
niques for problems solving in pharmaceutical technology
areas [12, 13]. The use of thermoanalytical methods in
pharmaceutical industry is necessary for the quality control
and for the development of new pharmaceutical formula-
tions [14, 15]. TG/DTA curves provide important infor-
mation regarding the physico-chemical properties of active
substance (stability, compatibility, kinetic analysis, and
polymorphism) [16–18]. The stability of a formulation can
be defined with the time in which this keeps its stability and
biological activity which is different of the chemical sta-
bility of the active substance when it is alone [19]. The
obtained information can be completed with the results of
hyphenate techniques which became essential in modern
methodologies of formulation development [20–23].
Due to the fact that thermal behaviour of HIDBCD was
not studied before, we set our goal in the investigation of
thermal degradation process in a dynamic air atmosphere and
Results and discussion
TG/DTG/DTA curves corresponding to the thermal behav-
-1
iour of HIDBCD at the heating rates 10 °C min in air
atmosphere are shown in Fig. 2. The TG curve indicated that
the thermal behaviour of HIDBCD was characterized by two
stages with a total mass loss of almost 100 % in 25–500 °C
temperature range. The first peak had an endothermic nature
and was assigned to the loss of water molecules from the
analysed cyclodextrin. The first mass loss process
(Dm = 5.40 %) which occurs in 25–204 °C temperature
range can be associated with the release of six molecules of
water from cyclodextrin (DTApeak = 99 °C).
Above 99 °C, DTA curve exhibits three processes with
the peak temperatures 217.1, 222.7, and 334.2 °C, respec-
tively. The first peak (217.1 °C) corresponds to an endo-
thermic event, namely, the phase transition (melting) of the
anhydrous cyclodextrin. The second and third events present
exothermic peaks and correspond to the degradation process
of the polysaccharide structure (see Fig. 2a).
-
1
in nitrogen atmosphere, at a heating rate of 10 °C min , up
to 500 °C, respectively, 600 °C.
Experimental
The HIDBCD is a commercial product and used as
received without further purification. It was obtained from
Acros Organics, Geel, Belgium and has a purity of 99.6 %.
The analysis of TG/DTG/DTA curves obtained in
nitrogen atmosphere reveals a similar thermal behaviour in
solid state for HIDBCD, namely in the temperature range
1
23

Thermal behaviour of a modified encapsulation agent
thermo-oxidations cannot occur, the mass loss process has
a slower tendency. Total mass loss in this case is 82 % at
600 °C, which is considerable lower than the one obtained
in air atmosphere at 500 °C. The difference can be
explained by the fact that degradation of HIDBCD up to
230 °C does not require the presence of oxygen and can be
associated with the molecular structure of the cyclodextrin.
After internal degradation of HIDBCD, the lack of oxida-
tive medium from nitrogen atmosphere restrains the
advanced degradation of cyclodextrin skeleton and
(
a)
100
60
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
0
50
TG
DTA
DTG
40
–3
3
2
0
0
–
–
–
6
9
10
obstructs the formation of CO (see Fig. 2).
2
-1
12
The EGA was carried out at a heating rate b = 20 °C min
0
in both nitrogen and air atmosphere. The temperature of the
EGA-FTIR device and transfer line is similar with the one
inside the furnace.
–10
–15
0
100
200
300
400
500
Temperature/°C
Gram–Schmidt profiles for the case in which the nitrogen
was used as carrier gas (Fig. 3a) indicated that the gaseous
products began to evolve at &230 °C and reached their
maximum releasing rate at 248 °C (t & 10 min) which
coincided with the DTGpeak (244 °C). At this point, the
EGA spectrum was recorded for the analysed cyclodextrin.
The FTIR spectra of the evolved gas from degradation
of HIDBCD drawn up in air/nitrogen atmosphere were
compared (Fig. 4a, b).
(
b)
1
00
4
1
20
9
0
0
0
0
0
0
0
0
0
0
TG
0
4
8
8
7
6
5
4
3
2
1
DTG
100
–
–
8
6
0
0
–
12
–16
20
–24
28
40
Similarity of the EGA spectra recorded in nitrogen at
different temperature values is observed throughout the
analysed process; the wavenumbers are identical and they
characterize the existence of the same compounds which
result from total breakdown of the initial cyclodextrin.
The main difference consists in the fact that in air
atmosphere, the mechanism of decomposition is different
than the one in nitrogen, fact sustained by the differences
of the absorption bands which appear in the spectra: in the
case of air thermo-oxidation, the presence of a sharp and
–
2
0
0
DTA
100
–
–20
600
0
200
300
400
500
Temperature/°C
Fig. 2 The TG, DTG, and DTA curves of HIDBCD in a air
atmosphere; b nitrogen atmosphere
-
1
strong band at m = 2,293 cm , characteristic for the
asymmetrical stretching vibration of CO molecules and at
2
5–204 °C, six molecules of water from cyclodextrin are
released, but at considerable lower temperature
DTApeak = 46 °C). This similar behaviour was expected,
2
-
1
a
m = 800 cm , characteristic for the bending suggest its
formation by the destruction of the hydrocarbonated chain.
These products identified in the EGA spectra are in
accordance with the molecular skeleton of HIDBCD and
demonstrate a significant destruction of the structure.
Regarding the degradation in inert atmosphere, it can be
(
due to the fact that formation of anhydrous cyclodextrin is
not influenced by the nature of the surrounding gas (air or
nitrogen). The degradation of HIDBCD in nitrogen is
similar with the one that occurs in air atmosphere, but only
up to 230 °C. DTA curve exhibits two processes with the
peak temperatures 210 and 219.5 °C, respectively. The
peak at 210 °C corresponds to an endothermic event,
namely, the melting of the anhydrous cyclodextrin. The
peak at 219.5 °C presents an exothermic effect and corre-
sponds to the degradation process of the HIDBCD (see
Fig. 2b).
noticed that the formation of CO
Another important bands that can be identified are the ones
molecules does not occur.
2
-
1
corresponding to CH
I
(2,955 cm
,
intense and
3
-
1
2,984 cm , intense), as well the ones corresponding to
degradation products of 6-deoxy-D-glucose: m(O–H) bands are
-
1
observed in the 3,500–3,200 cm spectral region. Further,
the resolution of this band is poor due to the overlap of m(O–H)
of water molecule. The vibrational frequencies of the ring for
At temperature higher than 230 °C, thermal behaviour
of HIDBCD is different in air atmosphere vs. nitrogen
atmosphere. Due to the fact that in nitrogen atmosphere,
the bending modes of dðOCH; CH and CCHÞ are observed at
2
-
1
1,460–1,340 cm
.
123

A. Fulia s¸ et al.
(
a)
100
(b)
100
120
550
120
100
80
5
450
00
5
5
4
00
50
90
9
8
7
6
5
4
3
2
0
0
0
0
0
0
0
0
0
4
1
00
0
8
0
0
TG
HF
DTG
TG
HF
DTG
T
–5
–10
–5
–10
–15
350
300
250
80
400
50
7
3
T
60
6
4
0
0
60
–15
300
250
50
–
–
20
25
–20
–25
40
200
40
2
1
1
5
00
50
00
0
30
20
10
0
150
100
50
20
0
–30
20
–
30
35
–
–
35
40
0
–
–40
–20
–45
–20
0
5
10
15
20
25
0
3
6
9
12
15
18
21
Time/min
Time/min
1
.4
.2
.0
.8
.6
.4
.2
.0
1.2
1.0
0.8
0.6
0.4
1
1
0
0
0
0
0
0.2
0.0
GS profile
15
GS profile
15
5
10
20
5
10
20
Time/min
Time/min
-
1
Fig. 3 Gram–Schmidt profile and thermoanalytical curves for HIDBCD (b = 20 °C min ); a nitrogen atmosphere; b air atmosphere
(
a)
(
(
240 °C)
248 °C)
(9.5 min)
(9.9 min)
2913
3312
1655
941 747
1149
1035
(
(
10.7 min)
11.4 min)
(
(
264 °C)
278 °C)
4000 3500 3000 2500 2000 1750 1500 1250 1000 750
500
Wavenumber/cm–1
4000 3600 3200 2800 2400 2000 1600 1200
800
400
Wavenumber/cm–1
Fig. 5 FTIR spectra for pure HIDBCD at 25 °C (top spectrum),
respectively, for remaining char after thermal treatment at 230 °C
(
b)
(
bottom spectrum) in air atmosphere
(
11 min)
(
250 °C)
(
(
12 min)
14 min)
(
270 °C)
The analysis of FTIR spectrum of HIDBCD before
thermal treatment reveals characteristic bands of the
polysaccharidic structure, namely: 3312, 2913, 1149, and
(
310 °C)
(
17 min)
400
-
1
(
370 °C)
1
,035 cm
which corresponds to the symmetric and
antisymmetric stretching of mOH, mCH, mC–C, and bending
vibration of mOH, respectively. The presence of the C–I
bond by the corresponding stretch band could not be
revealed by FTIR spectra, due to the fact that occurs at
4
000 3600 3200 2800 2400 2000 1600 1200
800
Wavenumber/cm–1
Fig. 4 FTIR spectra of gaseous mixtures observed for HIDBCD in
nitrogen (a) and air (b) measured by the online TG–FTIR system
-
1
wavenumbers between 200 and 500 cm [24]. Even if the
supplier does not mention the presence of water molecules
-
1
)
(
initial sample mass: 6.879 mg, heating rate: 20 °C min
1
23

Thermal behaviour of a modified encapsulation agent
in the cyclodextrin cavity, the FTIR spectra, corroborated
with thermal analysis, reveal its presence in the molecular
structure with the characteristic bending for H–O–H at
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By the analysis of the FTIR spectra of the cyclodextrin
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acteristic vibrational bands disappear, suggesting an
advanced destruction of the polysaccharide moieties. The
lack of bands obtained for this char suggests that it mainly
consist in carbon residues, which decompose with the
increasing of temperature, so at 500 °C, no remaining char
is observed. Corroborating these data with the ones
obtained by EGA technique, it is clearly that in the
2
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9
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Conclusions
A comparative thermal behaviour of HIDBCD in both air
and nitrogen atmosphere was realized. It was proved by
FTIR spectroscopy and thermal analysis that commercial
HIDBCD contains up to six molecules of water which are
released under heating with the formation of anhydrous
cyclodextrin. The degradation of HIDBCD in inert atmo-
sphere is similar with the one that occurs in air atmosphere,
but only up to 230 °C. Due to the fact that the inert
atmosphere prevents thermo-oxidations, the mass loss
process is considerably slower.
1
1
3. Anghel M, Vlase G, Bilanin M, Vlase T, Albu P, Fulias A, Tolan I,
Doca N. Comparative study on the thermal behavior of two similar
triterpenes from birch. J Therm Anal Calorim. 2013;113(3):
1379–85.
14. Fulias A, Ledeti I, Vlase G, Vlase T. Physico-chemical solid-state
characterization of pharmaceutical pyrazolones: an unexpected
thermal behaviour. J Pharm Biomed Anal. 2013;81–82:44–9.
Even if in nitrogen atmosphere the thermal behaviour
was studied up to 600 °C, a complete degradation of
molecular skeleton was not achieved; while in air atmo-
sphere, a mass loss of 99.9 % was reached at 500 °C. All
the data obtained from thermal curves were corroborated
with the ones obtained by FTIR spectroscopy and the ones
from TG–FTIR-hyphenated technique.
1
5. Fulias A, Vlase G, Grigorie C, Ledeti I, Albu P, Bilanin M, Vlase
T. Thermal behaviour studies of procaine and benzocaine.
J Therm Ana Calorim. 2013;113(1):265–71.
6. Fulias A, Ledeti I, Vlase G, Popoiu C, Heghe s¸ A, Bilanin M,
Vlase T, Gheorgheosu D, Craina M, Ardelean S, Ferechide D,
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1
Acknowledgements This work was supported by a grant from the
University of Medicine and Pharmacy ‘Victor Babe s¸ ’ Timi s¸ oara
17. Ledeti I, Simu G, Vlase G, Savoiu G, Vlase T, S¸ uta L-M, Popoiu
˘
C, Fulias A. Synthesis and solid-state characterization of Zn(II)
metal complex with acetaminophen. Rev Chim Bucharest.
(
Grant PIII-C1-CFI-2014/2015-03 to A.F.; I.L. and C.S.).
2
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1
8. Fulias A, Vlase G, Vlase T, Soica C, Heghes A, Craina M,
Ledeti I. Comparative kinetic analysis on thermal degradation of
some cephalosporins using TG and DSC data. Chem Cent J.
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