Caracterização e estudos de compatiblidade de desloratadina (em Inglês)

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1 23
Journal of Thermal Analysis and
Calorimetry
An International Forum for Thermal
Studies
 
ISSN 1388-6150
Volume 115
Number 3
 
J Therm Anal Calorim (2014)
115:2407-2414
DOI 10.1007/s10973-013-3271-4
Characterization and compatibility study
of desloratadine
Isabela P. Veronez, Josiane S. P. Daniel,
Jerusa S. Garcia & Marcello G. Trevisan
1 23
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Characterization and compatibility study of desloratadine
Isabela P. Veronez • Josiane S. P. Daniel •
Jerusa S. Garcia • Marcello G. Trevisan
Received: 27 March 2013 / Accepted: 24 May 2013 / Published online: 22 June 2013
� Akadémiai Kiadó, Budapest, Hungary 2013
Abstract Desloratadine (DL) is a selective antagonist of
the histamine H1 receptor, which has been widely used to
treat allergic symptoms, and stands out from other drugs in
this therapeutic class because it does not cause sedative
effects. In the present study, the physico-chemical prop-
erties of DL were fully characterized using six analytical
techniques such as Differential Scanning Calorimetry
(DSC), Thermogravimetric analysis (TG/DTG), Fourier
transform infrared spectroscopy (FT-IR), Raman spectros-
copy, Powder X-ray diffraction (PXRD), and scanning
electron microscopy (SEM). The DSC curve shows a sharp
endothermic event at 158.4 �C, and the TG/DTG curve
presents two decomposition events between 178.4 and
451.9 �C. A compatibility study involving DL and nine
pharmaceutical excipients generally used in pharmaceuti-
cal formulations was performed. Physical binary mixtures
of DL with each excipient were prepared in a 1:1 (w/w)
ratio. After preparation, the samples were analyzed
immediately and the results reveal solid-state interaction
with anhydrous lactose, microcrystalline cellulose, mag-
nesium stearate, and stearic acid.
Keywords Desloratadine � Compatibility � Thermal
analysis � Solid-state characterization
Introduction
Histamine H1 receptor antagonists inhibit the binding of
histamine to the histamine H1 receptor, prevent many of
histamine’s adverse effects, and are considered to be a first-
line therapy for the treatment of allergies. Most of the older
histamine H1 receptor antagonists have the potential for
adverse central nervous system effects and are character-
ized by poor receptor specificity [1].
Desloratadine (DL) is a potent and selective antagonist
of the histamine H1 receptor, which has been widely used
to treat allergic symptoms. DL does not cross the blood–
brain barrier and does not cause drowsiness or sedation. In
addition, DL effectively improves nasal and non-nasal
symptoms of allergic rhinitis and is not associated with
adverse cardiovascular or central nervous system effects
[1]. Chemically identified as 8-chloro-6,11-dihydro-11-(4-
piperdinylidene)-5H-benzo[5, 6]cyclohepta[1,2-b]pyridine,
DL is slightly soluble in water, but it is very soluble in
ethanol and propylene glycol [2].
Preformulation testing encompasses all studies on a new
drug and is an essential pre-requisite in the development of
new products, or for the reformulation of an existing one,
to produce useful information for the formulation of a
stable and biopharmaceutically suitable drug dosage form.
This stage includes the physico-chemical characterization
of the new drug, as well as stability and compatibility tests
with pharmaceutical excipients [3].
Presented orally at the 3rd Pan-American Congress of Thermal
Analysis and Calorimetry (CBRATEC 2012), Campos do Jordão, SP,
Brazil, 01–04 April 2012.
Electronic supplementary material The online version of this
article (doi:10.1007/s10973-013-3271-4) contains supplementary
material, which is available to authorized users.
I. P. Veronez � J. S. P. Daniel � J. S. Garcia �
M. G. Trevisan (&)
LACFar, Institute of Chemistry, Federal University of Alfenas
(UNIFAL-MG), Alfenas, Minas Gerais 37130-000, Brazil
e-mail: trevisan@unifal-mg.edu.br
M. G. Trevisan
National Institute of Science and Technology of Bioanalytical
(INCTBio), State University of Campinas, Campinas,
São Paulo 13084-653, Brazil
123
J Therm Anal Calorim (2014) 115:2407–2414
DOI 10.1007/s10973-013-3271-4
Author's personal copy
http://dx.doi.org/10.1007/s10973-013-3271-4
The characterization of solid-state properties at an early
stage by using appropriate analytical techniques is an
important step during the development of solid dosage
formulations, both from scientific and regulatory points of
view [4]. Furthermore, characterization tests provide
important information about the API particle shape, size,
polymorphism, and crystallinity to maintain pharmaceuti-
cal quality [4, 5]. Variations in the physico-chemical
properties of the pharmaceutical active ingredient (API)
may have an impact on therapeutic efficacy and on the
manufacturing, commercial, and legal aspects of drug
formulation [3, 4].
Most of the solid drugs that are intended for oral
administration require formulations with different excipi-
ents to allow appropriate administration, facilitate manu-
facturing, increase the stability of the formulations,
promote release and bioavailability of the drug, improve
patient compliance, and control the drug’s release in the
body [5, 6]. Although excipients have traditionally been
considered to be inert, several current studies have shown
that they can interact with the API included in the formu-
lation [4–6]. The successful formulation of a stable and
effective solid dosage form depends on careful selection of
excipients [7].
The study of drug–excipient compatibility, which is
recommended by the International Conference on Harmo-
nization (ICH), represents an important phase in the pre-
formulation stage for the development of all dosage forms.
The drug stability guidelines (Q1A) require that stability
tests of formulations should be conducted under acceler-
ated temperature and humidity conditions, with testing
occurring every 3 months [8]. In fact, potential physical
and chemical interactions between drugs and excipients
can affect the chemical nature, stability, and bioavailability
of drugs and, consequently, their therapeutic efficiency and
safety [9].
Thermal analyses such as differential scanning calo-
rimetry (DSC) have been widely used in preformulation
studies and routine pharmaceutical analyses, as it is a
versatile, fast, low-cost, and sensitive technique [9–12].
Solid-state interactions can be evaluated by thermal anal-
ysis, allowing the extraction of information about potential
physical or chemical incompatibilities between the API and
excipients, and contributing to the development of more
stable pharmaceutical formulations [9].
In this study, DL was fully characterized using six
analytical techniques, and its compatibility with nine dif-
ferent pharmaceutical excipients, commonly used in the
development of solid dosage forms, was evaluated.
Accordingly, DSC measurements were performed on each
of the components, both in their pure forms and the cor-
responding 1:1 (w/w) physical mixtures.
Experimental
Materials and samples
DL was provided by Dr. Reddys, India. Nine pharmaceu-
tical excipients generally used in pharmaceutical formula-
tions, and purchased from qualified pharmaceuticalsuppliers, were evaluated: dibasic calcium phosphate,
microcrystalline cellulose, corn starch, talc, mannitol,
magnesium stearate, polyvinylpyrrolidone K25 (PVP K25),
stearic acid, and anhydrous lactose.
Physical mixtures of DL with each excipient were pre-
pared in a 1:1 (w/w) ratio by simple mixture of the com-
ponents in a polyethylene container (3 cm 9 2 cm
diameter). The samples were homogenized using a vortex
and two stainless steel balls for 1 min. The 1:1 (w/w) ratio
was chosen to maximize the probability of observing any
interaction [9]. After preparation, the samples were ana-
lyzed immediately.
Methods
Thermogravimetric analysis (TG/DTG)
The TG/DTG curves were recorded on a thermogravimet-
ric analyzer Q600 (TA Instruments) employing the fol-
lowing parameters: a temperature range of 25–600 �C; a
dynamic nitrogen atmosphere (50 mL min-1); a heating
rate of 10 �C min-1; Al2O3 crucibles; and samples
weighing approximately 10 mg.
Powder X-ray diffraction (PXRD)
X-ray diffraction patterns of DL were obtained with an
Ultima IV diffractometer (Rigaku), operating at 40 kV and
30 mA, using Cu Ka source. The measurements of 2h
ranged between 5� and 55� (±0.02).
Fourier transform infrared spectroscopy (FT-IR)
Infrared spectra (FT-IR) of the drug, excipients, and binary
mixtures were obtained using an IRPrestige – Shimadzu
spectrometer and employing potassium bromide disks in
the range of 2,000–400 cm-1. Each spectrum was the
average of more than 20 consecutive scans on the same
sample using a spectral resolution of 8 cm-1.
Raman spectroscopy
Raman spectra were recorded at room temperature using a
RamanStation 400F (PerkinElmer) equipped with a
785 nm excitation laser and an attachment for solids. Each
2408 I. P. Veronez et al.
123
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spectrum was the average of four scans from 2,000 to
200 cm-1, using 1 cm-1 of spectral resolution.
Scanning electron microscopy (SEM)
SEM micrographs were obtained with a JSM-6340F Field
Emission–JEOL microscope. The samples were vacuum
coated with gold and analyzed directly by SEM (5009/
10,0009).
Differential scanning calorimetry (DSC)
Studies of the compatibility between API and excipients
were achieved by analysis of the DSC curves of the drug,
the excipients, and mixtures of the two components in 1:1
ratios (w/w). DSC experiments were conducted using a
high-sensitivity differential scanning calorimeter, model
DSC-7020 EXSTAR (SII NanoTechnology Inc.). Samples
(approx. 3.3 mg) were placed in open aluminum crucibles
and heated from an initial temperature of 25 �C to a final
temperature of 180 �C at 10 �C min-1, under a dynamic
nitrogen atmosphere (50 mL min-1). The DSC cell was
previously calibrated with indium (purity greater than
99.99 %, Tonset = 156.6 ± 0.3 �C, and heat of fusion of
28.6 ± 0.5 J g-1).
Results and discussion
Characterization of DL
In the first phase of this study, DL was fully characterized
by six analytical techniques. The TG/DTG and DSC curves
obtained for DL are shown in Fig. 1a. Thermal decompo-
sition of DL in a nitrogen atmosphere occurs in two steps
and begins at 178.4 �C. The temperature range of decom-
position is from 178.4 to 451.9 �C, with the total mass loss
of 97.1 % and DTG peak at 340.8 �C. The DSC curve of
DL shows a well-defined endothermic event, indicating
melting at 158.4 �C (Tonset = 156.4 �C and
DHfus = 105 J g
-1). In this temperature range, the TG/
DTG curves did not show mass loss.
To evaluate the stability of polymorphic forms, a cyclic
DSC (CDSC) experiment was performed. Approximately
3 mg of DL was maintained in the isotherm for 3 min at
180 �C, after the end of the fusion event. The crucible was
then cooled at a rate of 10 �C min-1 to a final temperature
of 25 �C. No exothermic peak of DL recrystallization was
observed. After cooling, the same sample was reheated at a
rate of 10 �C min-1 up to a final temperature of 300 �C,
and the curve did not show any thermal events, as shown in
Fig. 1b.
This sample was analyzed by X-ray diffraction to
investigate its nature. Powder X-ray diffractometry is a
powerful technique for the identification of crystalline solid
phases and determination of the degree of crystallinity [13,
14]. Prior to the thermal analysis, the sample showed
strong peaks at 12.14, 13.14, 18.68, 20.08, 21.16, 26.3, and
29.24�2h, which is characteristic of Form 1 crystallinity
[15] (Fig. 2a). However, after subjecting the DL to CDSC,
it did not show peaks (Fig. 2a) and was characterized as
amorphous. Thus, the heating process applied to the sample
was efficient in achieving amorphization of the API.
The SEM micrographs of the samples, both before and
after CDSC, obtained at magnification 5009 and 10,0009,
are presented in Fig. 2b. The morphological analysis of the
API before and after CDSC confirmed that the heating was
efficient at achieving amorphization of the API. Irregularly
shaped particles, including aggregates of flakes, were
visualized in the sample before CDSC [16]. In contrast, a
fused mass with agglomerated particles was observed in
the sample after CDSC.
In addition to the diffractogram data, the FT-IR spectra
of the samples, both before and after CDSC, were obtained
to evaluate the thermal stability of the API. The spectra of
DL before CDSC (Fig. 3a-I) show prominent bands at
1,479 and 1,435 cm-1, which is attributed to the C–C
stretching of aromatic rings, while the bands at 1,177 and
779 cm-1 correspond to C–N amines and C–Cl stretching,
respectively. These results are in agreement with other
published data [17]. The spectra of DL obtained after
CDSC (Fig. 3a-II) show the same absorption bands, indi-
cating that the DL did not decompose in the range of
applied temperatures. Therefore, DL is sufficiently ther-
mally stable to allow analysis by the DSC method.
Raman spectroscopy was used to complement the data
obtained by FT-IR. The Raman spectra of DL, both before
and after CDSC, were recorded at ambient conditions
(Fig. 3b). The spectra show strong bands at 1,635 and
1,585 cm-1, corresponding to C=N stretching and C=C
stretching of aromatic rings, respectively, and a band at
689 cm-1 which is attributed to C–Cl stretching.
Compatibility studies with excipients
DSC has been proposed to be a rapid method for evaluating
the physico-chemical interactions between components of
formulations and, therefore, to aid in the selection of ex-
cipients with suitable compatibility [9–11].
The DSC curves obtained for DL and the tested excip-
ients are shown in Fig 4a. Each curve shows unique
behavior, depending on the characteristics of each excipi-
ent. None of the excipients showed any thermal event near
the melting peak of DL; thus, it was possible to investigate
the interactions between the components of binary
Characterization and compatibility study of desloratadine 2409
123
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mixtures of drug and excipient by comparing the temper-
ature profiles obtained for the mixtures with those of their
individual components [4, 5, 10, 11].
The possible interactions between components are
deduced from DSC curves by examining the appearance,
shift, or disappearance of DSC peaks, especially the
melting peak, and/or variations in the expected enthalpy
(DH) values. An interaction was assumed to result in a
decrease or, in the case of overlapping, an increase in the
enthalpy, which is a more complex process [9].
The thermo-analytical data regarding isolated DL and
the physical mixtures, obtained from the thermal curves,
are presented in Table 1. The data show that the thermal
profile of DL, particularly the parameters of fusion (Tonset
and DHfus), remained almost constant in the binary mix-
tures for the majority of the tested excipients. In a practical
sense, the thermal curves of binary mixtures can be con-
sidered as superpositions of the individual curves of DL
and the excipients. However, for mixtures containing
microcrystallinecellulose, magnesium stearate, stearic
acid, and anhydrous lactose, there were some changes with
the API melting temperature and enthalpy, as shown in
Fig. 4b.
For mixtures containing anhydrous lactose, there was a
small decrease in the value of the melting peak, which is a
sign of possible solid–solid interactions but not necessarily
an indication of chemical incompatibility between the drug
and excipient. Anhydrous lactose is a reducing sugar with
the potential to interact with primary and secondary amines
when stored under conditions of high humidity for exten-
ded periods [18]. Anhydrous lactose is employed as a dil-
uent for tablets and capsules, and several incompatibilities
[18–20] and compatibilities [21] with other APIs are
reported in the literature.
The values obtained from the heat of fusion were
compared statistically by using an analysis of variance. The
1 % significance test showed that the composition of the
mixture influences the value of the enthalpy (p \ 0.0001).
The Scott–Knott test was performed to compare the mean
values (data not shown). After analyzing the data, a sta-
tistically significant change in the heat of fusion was
observed for the blends containing excipients, such as
0
100
a
b
50
0
–500
–1000
H
ea
t f
lo
w
/W
 g
–1
M
as
s 
lo
ss
/%
–1500
E
nd
o
100
0
–400
–800
–1200
–1400
30 60 90 120 150 180 210 240 270 300
200 300
Temperature/°C
400 500 600
D
er
iv
at
iv
e 
m
as
s/
%
 °
C
–1
DSC
DTG
TG
0.5
0.0
–0.5
–1.0
–1.5
–2.0
H
ea
t f
lo
w
/W
 g
–1
Temperature/°C
E
nd
o
Tp = 158.4 °C
1st Heating
Cooling
2nd Heating
Fig. 1 TG/DTG and DSC
curves of DL (a) and CDSC
curves of DL (b)
2410 I. P. Veronez et al.
123
Author's personal copy
microcrystalline cellulose, anhydrous lactose, magnesium
stearate, and stearic acid, which may indicate interactions
between these components and the API.
The differences in enthalpy between the binary mixtures
containing microcrystalline cellulose and those containing
anhydrous lactose suggest physical interactions, but not
chemical incompatibilities (degradation products). The
microcrystalline cellulose is used as a tablet and capsule
diluent and as a tablet disintegrant [18], and some inter-
actions between this excipient and drugs, such as the
production of enalapril maleate, are detailed in the litera-
ture [22].
The most obvious changes were observed in the mixture
containing stearic acid, in which the endothermic peak
relating to the melting point of DL disappeared and the
signals of stearic acid were altered, indicating the occur-
rence of a strong interaction between the components as the
temperature changed. The appearance of a new peak at
99.1 �C shows a clear chemical interaction between the
components of the binary mixture (Fig. 5a).
100a
b
80
60
40
R
el
at
iv
e 
in
te
ns
ity
/%
20
0
5 10 15
(I) (II)
20 25 30
2θ/°
35 40 45 50 55
Before CDSC
After CDSC
Fig. 2 PXRD of DL before and
after CDSC (a) and SEM
photomicrographs of DL at
5009 and 10,0009
magnification (b): (I) before
CDSC; (II) after CDSC. (Color
figure online)
Characterization and compatibility study of desloratadine 2411
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Stearic acid and magnesium stearate are used as lubri-
cants to improve the flow properties of the mixtures and
reduce the loss during compression [5, 18]. Several inter-
actions in pharmaceutical formulations between magne-
sium stearate and drugs, such as ketoprofen, captopril,
ibuproxan, and ibuprofen, are detailed in the literature
[5, 7, 9, 20]. Magnesium stearate cannot be included in
products containing aspirin, those containing certain vita-
mins or most alkaloidal salts [18].
Commercially available magnesium stearate is a mix-
ture of long-chain aliphatic acids with variable water
content [23]. The DSC curves of the DL/magnesium stea-
rate mixture showed three endothermic events, with the
first occurring at approximately 80–110 �C, a second
occurring at 110–130 �C, and a third occurring at
155–160 �C. The first event is attributable to a loss of
water from the hydrated state of the magnesium stearate,
the second event indicates that the material melted at this
point [4, 23], and the third event corresponds to the melting
point of DL (Fig. 5b). In the mixture containing magne-
sium stearate, a slight reduction in the melting enthalpy of
the DL was observed, an alteration that can be explained by
the partial solubility of the DL in the excipient as mag-
nesium stearate melts around 130 �C, which is below the
melting point of the API.
FT-IR spectroscopy was used as a supplementary tech-
nique to investigate the possible chemical interactions
between the drug and excipients. The appearance of new
absorption bands, broadening of the absorption bands, and
alterations in their intensity are the main signals of inter-
actions between the drug and excipients [9, 24].
2000
I
a
II
Tr
an
sm
ita
nc
e/
%
R
el
at
iv
e 
in
te
ns
ity
/%
1600 1200
Wavenumber/cm–1
800 400
200 400 600 800 1000
Raman shift/cm–1
1200 1400
I
II
1600 1800 2000
b
Fig. 3 FT-IR spectra (a) and Raman spectra (b) of DL: before (I) and
after (II) CDSC
E
nd
o
DL
a
Dibasic calcium phosphate
Microcrystalline cellulose
Corn starch
Talc
Mannitol
Magnesium stearate
PVP
Stearic acid
Anhydrous lactose
30 60 90 120
Temperature/°C
150 180
DL
DL + Dibasic calcium phosphate
DL + Microcrystalline cellulose
DL + Corn starch
DL + Talc
DL + Mannitol
DL + Magnesium stearate
DL + PVP
DL + Stearic acid
DL + Anhydrous lactose
E
nd
o
30 60 90 120
Temperature/°C
150 180
b
Fig. 4 DSC curves of DL and excipients (a) and DSC curves of DL
and binary mixtures (b)
2412 I. P. Veronez et al.
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The spectra of the drug and all tested excipients were
obtained for the pure compounds, as well as for binary
mixtures of the two components in 1:1 ratios (w/w), to
identify possible chemical interactions between the two
species. The FT-IR spectra show that the characteristic
bands of DL and each excipient individually were not
altered in binary mixtures, which indicates no interactions
between DL and the selected excipients when immediate
contact is established at room temperature (supplementary
material).
X-ray diffraction is another approach used for qualita-
tive and quantitative determination of crystallinity to
investigate the possible interactions between DL and ex-
cipients. Such interactions between the drugs and excipi-
ents, observed in the DSC curves, should result in the
partial or complete disappearance of the reactant phases
and appearance of new phases. These changes can be
inferred from X-ray diffraction patterns. X-ray diffraction
patterns of the mixture, as prepared at room temperature,
when compared to the patterns produced by the individual
components, show the appearance of new lines and the
disappearance of some of the lines characteristic to the
individual components [9, 24]. The diffractograms of two
of the binary mixtures—DL/stearic acid and DL/magne-
sium stearate—do not show the appearance of new lines in
the XRD patterns (supplementary material). These results
indicate that there are no interactions between DL and
these excipients when immediate contact is established at
room temperature. However, the interactions could
increase if the temperature was increased.
Conclusions
The solid-state characterization of crystalline forms of drug
candidates is important to the pharmaceutical development
process. In this study, DL was fully characterized using
thermal analyses (DSC, TG), FT-IR, Raman, PXRD, and
SEM, demonstrating the drug’s physico-chemical proper-
ties. The CDSC reaction confirmed that the heating process
applied to the sample was efficient at achieving amorph-
ization of the API. FT-IR spectra confirmed the thermal
stability of the API within the working temperature range,
which indicates that analysisby DSC is appropriate.
Table 1 Thermo analytical fusion event data for DL in different physical mixtures (n = 3)
Sample Tonset/�C Tf/�C Tpeak/�C DHf/J g-1
Desloratadine (DL) 156.4 ± 0.2 161.3 ± 0.1 158.4 ± 0.1 105.0 ± 0.2
DL ? dibasic calcium phosphate 155.6 ± 0.1 160.3 ± 0.4 158.5 ± 0.5 51 ± 3
DL ? microcrystalline cellulose 155.4 ± 0.1 162.0 ± 0.5 158.2 ± 0.1 44 ± 5
DL ? corn starch 155.5 ± 0.1 162.6 ± 0.3 158.5 ± 0.4 50 ± 2
DL ? talc 155.7 ± 0.1 161.1 ± 0.6 158.2 ± 0.1 47.5 ± 0.7
DL ? mannitol 151.9 ± 0.2 157.2 ± 0.3 154.6 ± 0.2 56 ± 4
DL ? magnesium stearate 155.10 ± 0.01 161.0 ± 0.7 157.8 ± 0.1 37 ± 3
DL ? PVP 151.2 ± 0.3 159.8 ± 0.5 156.3 ± 0.1 56 ± 7
DL ? stearic acid 94.6 ± 0.4 101.3 ± 0.2 99.1 ± 0.2 39 ± 2
DL ? lactose anhydrous 150.1 ± 0.1 158.1 ± 0.5 155.10 ± 0.01 42 ± 1
0
a
–500
–1000
H
ea
t f
lo
w
/W
 g
–1
–1500
30 60 90
Temperature/°C
120
DL
Stearic acid
DL + Stearic acid
150 180
0
–500
–1000
H
ea
t f
lo
w
/W
 g
–1
–1500
DL
Magnesium stearate
DL + Mg stearate
30 60 90
Temperature/°C
120 150 180
b
Fig. 5 DSC curves of DL, excipient, and 1:1 binary mixtures (w/w):
DL/Stearic acid (a); DL/magnesium stearate (b)
Characterization and compatibility study of desloratadine 2413
123
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In the compatibility studies with excipients, the DSC
results indicated that the dibasic calcium phosphate, corn
starch, and talc present in the binary mixtures were stable
and that there was no incompatibility between the DL and
these excipients. However, preliminary interactions may be
presumed in the case of mixtures containing microcrys-
talline cellulose, anhydrous lactose, magnesium stearate,
and stearic acid. These results confirm the utility of DSC in
preformulation studies, as it is a fast and appropriate
technique for determining the most suitable excipients.
Additionally, FT-IR and X-ray analyses were per-
formed, and no evidence of solid-state interaction or
incompatibility was observed when immediate contact
between the components was established at room
temperature.
Acknowledgements This study was supported by FAPEMIG
(Process APQ-04835-10) and CAPES (Fellowship). The authors
would like to thank the Laboratory of Crystallography/UNIFAL-MG
for PXRD analysis and the Institute of Chemistry/UNICAMP for
SEM microscopies.
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2414 I. P. Veronez et al.
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http://dx.doi.org/10.1007/s10973-012-2476-2
	Characterization and compatibility study of desloratadine
	Abstract
	Introduction
	Experimental
	Materials and samples
	Methods
	Thermogravimetric analysis (TG/DTG)
	Powder X-ray diffraction (PXRD)
	Fourier transform infrared spectroscopy (FT-IR)
	Raman spectroscopy
	Scanning electron microscopy (SEM)
	Differential scanning calorimetry (DSC)
	Results and discussion
	Characterization of DL
	Compatibility studies with excipients
	Conclusions
	Acknowledgements
	References