Loratadine, ethyl 4-(8-chloro-5,6-dihydro-11H-
piperidinecarboxylate is a long acting non-sedative
antihistaminic agent that was developed for the treat-
ment of seasonal allergic rhinitis  whose action is
more effective than the other commercially available
antihistaminic drugs. It is a white to off-white pow-
der, m.p. 136°C, not soluble in water, but very soluble
in acetone, alcohol, ether and chloroform . The
structural formula of loratadine is:
Thermal analytical techniques can provide im
portant information regarding storage and stability of
pharmaceuticals. Examples of the importance of such
studies are given in [3, 4].
Solid-state kinetic studies have increasing im
portance in thermal analysis, in which the main pur
poses are to calculate the parameters of the Arrhenius
equation and to determine the mechanism(s) of pyrol
ysis reaction. These data can provide valuable infor
mation about time and condition of storage. The
knowledge of such parameters for pure drugs and for
drug–excipient mixtures is also meaningful in order
to elucidate miscibility/incompatibility and its effects
on thermal stability.
In this work TG/DTG and DTA were used to char-
acterize the decomposition pathways of loratadine both in
air and nitrogen atmospheres. Flynn–Wall–Ozawa
method [5, 6] was used for kinetic analysis on the thermal
decomposition of loratadine, since few information on E
of the thermal decomposition of loratadine obtained from
TG/DTA analysis is reported in the literature.
Loratadine, pharmaceutical grade min. 99.48% (Natu
ral Pharma, Brazil) was used without further purifica
tion. Simultaneous TG/DTG - DTA runs were carried
out with initial sample mass of 7.0 mg, in alumina pans
(90 μL), using simultaneous SDT-Q600 equipment
(TA Instruments). Dynamic nitrogen and air atmo
spheres (flow rate of 50 mL min
) and heating rates
of 2, 4, 8, 12, 16 and 32°C min
were used. The appa
ratus was calibrated for temperature with zinc stan
dard. For the kinetic study, the experiments were per
formed at least in duplicates, using the above described
conditions. Standard calibration weights were used for
mass calibration recommended by TA Instruments in
Thermal Advantage for Q-Series software.
DSC curves were recorded using 3.0 mg of ini
tial sample mass, a covered aluminum pan with a cen
1388–6150/$20.00 Akadémiai Kiadó, Budapest, Hungary
© 2007 Akadémiai Kiadó, Budapest Springer, Dordrecht, The Netherlands
Journal of Thermal Analysis and Calorimetry, Vol. 87 (2007) 3, 831–834
THERMAL BEHAVIOR OF LORATADINE
L. A. Ramos and É. T. G. Cavalheiro
Departamento de Química e Física Molecular, Instituto de Química de S±o Carlos, Universidade de S±o Paulo
Av. do Trabalhador S±o-Carlense, 400 Centro, Caixa Postal 780, CEP: 13560-970 S±o Carlos, SP, Brazil
Simultaneous thermogravimetry (TG) and differential thermal analysis (DTA) techniques were used for the characterization the ther
mal degradation of loratadine, ethyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidine)-1-piperidine
carboxylate. TG analysis revealed that the thermal decomposition occurs in one step in the 200–400°C range in nitrogen atmosphere.
DTA and DSC curves showed that loratadine melts before the decomposition and the decomposition products are volatile in nitrogen.
In air the decomposition follows very similar profile up to 300°C, but two exothermic events are observed in the 170–680°C tempera
Flynn–Wall–Ozawa method was used for the solid-state kinetic analysis of loratadine thermal decomposition. The calculated
activation energy (E
for α between 0.02 and 0.2, where the mass loss is mainly due to the decomposition than to
the evaporation of the decomposition products.
Keywords: decomposition kinetic, DTA, loratadine, thermogravimetry
* Author for correspondence: firstname.lastname@example.org
tral pinhole in the lid, 10°C min
heating rate under
nitrogen flow. TA DSC-910 unit cou
pled to a TA-2000 Thermal Analyzer (both from TA
Instruments). Temperature and enthalpy calibration
of the equipment have been done using metal indium
with 99.99% purity.
Results and discussion
Thermal decomposition of loratadine in nitrogen at
mosphere lead to 100% mass loss between 200
and 400°C (Fig. 1a).
The thermal decomposition in air starts at 170°C
and about 80% mass loss occurs in the first step (up
to 410°C) resulting a carbonaceous residue, (Fig. 1b).
Between 410 and 680°C, the remaining 20% of initial
mass is lost in a second decomposition step, accompa
nied by the burning of the carbonaceous residue.
The DTG curve in nitrogen atmosphere exhibits
one peak (peak temp.: 345°C). The DTG curve in air
atmosphere shows two peaks at 332 and 533°C.
In nitrogen the endothermic peak at 137°C is re
lated to the melting of the sample (DTA curve, Fig. 2a)
while the broader one at 345°C (in agreement with
TG/DTG data) is due to the evaporation of the sample.
Small amount of loratadine was heated in a 20 cm
long open glass tube, under nitrogen. It was observed
that heated up to 300°C a non-volatile liquid was ob-
tained. The non-volatile nature of the liquid was con-
firmed since no any drops referring to condensation
have been observed in the cold part of the tube. When
the temperature reached 320°C the liquid becames yel-
lowish and a liquid condensate was observed in the up-
per part of the tube. At 350°C the liquid becomes
brownish and evaporates without condensation.
Under air (Fig. 2b) an endothermic melting peak
was observed at 137°C. However, in this case the de
composition was represented by two exothermic
events with peaks at 332 and 525°C. A peak at 618°C
represents the burning of the carbonaceous residue.
A DSC curve obtained under nitrogen (Fig. 3)
shows the melting endotherm at 138°C (ΔH
33.2 kJ mol
). Then the decomposition can be ob
served starting with a small exotherm peak followed
832 J. Therm. Anal. Cal., 87, 2007
Fig. 1 —–TGand⋅⋅⋅ – DTG curves of loratadine in
a – nitrogen andb–air
Fig. 2 DTA curves of loratadine in a – nitrogen andb–air
Fig. 3 DSC curve of loratadine in nitrogen
by a broad endotherm one at 376°C and again an
exotherm appears at 415°C.
This is in agreement with the observation of the
heating in an open tube (see above).
Thus one can conclude that upon heating the
thermal behavior of loratadine involves a fusion, fol
lowed by decomposition and evaporation of the de
Considering that loratadine in liquid state is not vola
tile, but only its decomposition products evaporate,
the kinetic parameters were calculated as it is
Non-isothermal kinetic analysis was based on
TG experiments performed at six different heating
rates 2, 4, 8, 12, 16, 32°C min
in nitrogen atmo
sphere (flow rate of 50 mL min
). The TG and DTG
curves shifted to higher temperatures with increasing
heating rates (Figs 4 and 5).
Therefore, Ozawa–Flynn–Wall equation (Eq. (1))
was applied to describe the overall degradation reac
tion and the activation energy was calculated as a func
tion of the degree of reaction.
log – . – .
log – log[
0 4567 23115
where β – heating rate, E
– apparent activation energy,
R – gas constant, T – absolute temperature, A – pre-ex
ponential factor and g(α) – mathematical expression
related to the TG curve. Guinesi et al.presentedade
tailed description how Eq. (1) was obtained .
Straight lines were obtained for the logβ vs.1/T
plots (Fig. 6). Between α=0.02–0.9, when α>0.1, the
correlation coefficients are larger than 0.999.
Figure 7 shows the dependence of the activation
energy as a function of conversion (%). There are lin
ear parts, suggesting changes in the decomposition
mechanism. The first related to the decomposition of
J. Therm. Anal. Cal., 87, 2007 833
THERMAL BEHAVIOR OF LORATADINE
Fig. 4 TG curves of loratadine at different heating rates under
dry nitrogen atmosphere.a–2,b–4,c–8,d–12,
e – 16 and f – 32°C min
Fig. 5 Overlaid DTG curves of loratadine using different heat
ing rates under dry nitrogen atmosphere.a–2,b–4,
Fig. 6 logβ vs.1/T plots for loratadine ata–2,b–5,c–10,
Fig. 7 Dependence of the activation energy vs. degree of con
version for loratadine in nitrogen for 0.06<α<0.9
the liquid loratadine, the second is representative to a
process involving decomposition and evaporation of
the decomposition products and the third one mostly
related to the evaporation of the brownish decomposi
tion product (see above).
These results suggested E
in the first linear portion where the
mass loss is the mainly due to the thermal decomposi
tion, in the 0.06<α<0.22 range.
These studies suggest that the decomposition of
loratadine occurred after melting in a single step in ni
trogen atmosphere, when the sample is heated from 300
to 350°C, with E
and A=7.2±0.2 min
Only the decomposition products are volatile. In air af
ter melting decomposition took place with the formation
of carbonized residue.
1 G. G. Kay and A. G. Harris, Clin. Expert Allergy,
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2 The Merck Index, 12
Edition, Merck and Co., Inc.,
Rahway, NJ, USA 1996.
3 A. C. Schmidt, J. Therm. Anal. Cal., 81 (2005) 291.
4 L. C. S. Cides, A. A. S. Araujo, M. Santos-Filho and
J. R. Matos, J. Therm. Anal. Cal., 84 (2006) 441.
5 T. Ozawa, Bull. Chem. Soc. Jpn., 38 (1965) 1881.
6 J. H. Flynn and L. A. Wall, J. Polym. Sci., B4 (1966) 323.
7 L. S. Guinesi, C. A. Ribeiro, M. S. Crespi, A. F. Santos
and M. V. Capela, J. Therm. Anal. Cal., 85 (2006) 301.
834 J. Therm. Anal. Cal., 87, 2007