Thermal behavior of loratadine

Abstract and Figures

Simultaneous thermogravimetry (TG) and differential thermal analysis (DTA) techniques were used for the characterization the thermal degradation of loratadine, ethyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidine)-1-piperidinecarboxylate. 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 temperature range. Flynn–Wall–Ozawa method was used for the solid-state kinetic analysis of loratadine thermal decomposition. The calculated activation energy (E a) was 91±1 kJ mol–1 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.
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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 [1] 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 [2]. 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
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
ture range.
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:
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 behavior
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
composition product.
Kinetic studies
Considering that loratadine in liquid state is not vola
tile, but only its decomposition products evaporate,
the kinetic parameters were calculated as it is
described below.
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 [7].
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
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,
c–8,d–12,e–16andf–32°C min
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
A=7.2±0.2 min
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,
29 (1999) 147.
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.
DOI: 10.1007/s10973-006-7752-6
834 J. Therm. Anal. Cal., 87, 2007
... DTA thermograms of loratadine, succinic acid, cocrystal phase, both powder and tableted samples, are presented in Figure 3. Loratadine exhibited single endothermic peak of melting event at 136.4ºC [17]. Succinic acid exhibits two endothermic peaks at 190 and 250ºC attributed to melting and evaporation event, respectively [18]. ...
... Figure 3 shows thermograms of loratadine, succinic acid, physical mixture, and cocrystal phase. Thermogram of pure loratadine and succinic acid exhibited a single endothermic peak at temperature of 137.5°C and 189.3°C, respectively, due to the melting event [24][25][26]. Physical mixture of loratadine-succinic acid revealed two broad endothermic peaks at 120.9 and 176.6°C. It has been known that physical mixture of cocrystal components has specific thermogram containing two endothermic peaks attributed to eutectic and cocrystal melting [27,28]. ...
Objectives Loratadine belongs to Class II compound of biopharmaceutics classification system (BCS) due its low solubility and high membrane permeability. Cocrystal is a system of multicomponent crystalline that mostly employed to improve solubility. Succinic acid is one of common coformer in cocrystal modification. This research aims to investigate cocrystal formation between loratadine and succinic acid and its effect on solubility property of loratadine. Methods Cocrystal of loratadine-succinic acid was prepared by solution method using methanol as the solvent. Cocrystal formation was identified under observation of polarization microscope and analysis of the binary phase diagram. The cocrystal phase was characterized by differential thermal analysis (DTA), powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Solubility study was conducted in phosphate-citrate buffer pH 7.0 ± 0.5 at 30 ± 0.5 °C. Results Loratadine is known to form cocrystal with succinic acid in 1:1 M ratio. Cocrystal phase has lower melting point at 110.9 °C. Powder diffractograms exhibited new diffraction peaks at 2 θ of 5.28, 10.09, 12.06, 15.74, 21.89, and 28.59° for cocrystal phase. IR spectra showed that there was a shift in C=O and O–H vibration, indicating intermolecular hydrogen bond between loratadine and succinic acid. SEM microphotographs showed different morphology for cocrystal phase. Loratadine solubility in cocrystal phase was increased up to 2-fold compared to loratadine alone. Conclusions Cocrystal of loratadine and succinic acid is formed by stoichiometry of 1:1 via C=O and H–O interaction. Cocrystal phase shows different physicochemical properties and responding to those properties, it shows improved loratadine solubility as well.
... The thermal behavior of pharmaceuticals is crucial as it can provide important information regarding formulation stability. In addition, it may reveal incompatibilities between the drug and excipients [30]. The TG curve for ABAM shows only one well-defined stage of mass loss, which is related to its volatilization ( Figure 4). ...
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α,β Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed to develop solid dispersions (SD) of ABAM with the following hydrophilic polymers: polyvinylpyrrolidone (PVP-K30), polyethylene glycol (PEG-6000) and hydroxypropylmethylcellulose (HPMC). The SDs were prepared by physical mixture (PM), kneading (KND) and rotary evaporation (RE) methods. In order to verify any interaction between ABAM and the hydrophilic polymers, physicochemical characterization was performed by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC) analysis. Furthermore, an in vitro anti-inflammatory assay was performed with ABAM alone and as SDs with the hydrophilic polymers. The results from the characterization analysis show that the SDs were able to induce changes in the physicochemical properties of ABAM, which suggests interaction with the polymer matrix. In vitro anti-inflammatory assay showed that the SDs improved the anti-inflammatory activity of ABAM and showed no cytotoxicity. In conclusion, this study showed the potential use of SDs as an efficient tool for improving the stability and anti-inflammatory activity of ABAM without cytotoxicity.
The main goal of this study was to develop immediate release Fused Deposition Modeling (FDM) 3D printed loratadine tablets using hot-melt extrusion (HME) filaments. Loratadine was used as a model drug with 10% (w/w) drug loading. Ten different formulations were prepared using Crospovidone and croscarmellose as super-disintegrants, mannitol as a pore-forming agent, and polyethylene oxide-N80 and hydroxypropyl cellulose-EF as polymeric carriers. A three-point bend test was performed to determine the filaments' elasticity, strength, and stiffness in order to evaluate the filaments printability. The printable filaments were then printed using an (Prusa i3 MK3S) FDM-3D printer in a grid pattern and with (40–60%) infill to accelerate the drug release. The physical mixtures, filaments, and 3D printed tablets were analyzed using differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) was performed to investigate the interactions between loratadine and polymeric carriers. The in-vitro drug release profile of the printed tablets was tested. Based on the filament's mechanical properties, six filaments were printable. The DSC thermograms indicated complete solubilization of loratadine in the polymeric carrier. All printed tablets exhibited a drug release of (86.1–96.9%) in 30 minutes. HME showed great potential to develop immediate release filaments which were suitable for FDM-3D printing.
Loratadine, 4-(8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylic acid ethyl ester, is an antihistamine drug with long-acting effects and has limited selectivity for peripheral H1 receptors. It is widely used for the prevention of allergic diseases such as rhinitis chronic urticaria, and asthma. This chapter discusses, by a critical extensive review of the literature, the description of loratadine in terms of its names, formulae, elemental composition, appearance, methods of preparation. The profile contains physicochemical properties of Loratadine, including pKa value, solubility and X-ray powder diffraction. In addition, it involves Fourier transform infrared spectrometry, nuclear magnetic resonance spectroscopy and mass spectroscopy for functional groups and structural confirmation of. The chapter also includes methods of analysis of the drug such as compendial, titrimetric, electrochemical, spectroscopic, chromatographic and capillary electrophoretic methods. The chapter also covers clinical applications of the drug such as its uses, doses, ADME profiles and mechanism of action.
The aim of this study was to assess the impact of a sample pan together with the atmosphere of the measurement on the kinetics of thermal degradation of the strongly sublimating, antiepileptic drug – carbamazepine (CBZ). The fusion-cooling or annealing-cooling cycle was conducted under inert gas or an oxidative atmosphere for samples that were placed in either open or hermetically sealed pans. The thermal behavior of the samples was investigated using DSC, HPLC and ATR FT-IR spectroscopy. The samples that were fused or annealed in the open pans underwent only a phase transition, whereas these that were treated in the hermetically sealed pans partially degraded. Furthermore, when performing the TGA measurements coupled with FT-IR, there were no differences in the degradation kinetics between the inert gas and oxidative atmosphere up to 650 K. Above that temperature, there was an additional weight loss, associated with the combustion of an organic residue, for the sample that was heated in the oxidative atmosphere.
Objective The present study involved enhancement of Meloxicam (MX) oral absorption for rapid onset of therapeutic action. A challenging approach using hot-melt-extrusion technique (HME) for production of stable novel preparation of MX pellets was successfully proposed. Methods Manipulating HME processing parameters (barrel-temperatures and screw-speed) and proper polymer(s) selection (Soluplus, a combination of Soluplus/Poloxamar and Polyethylene Glycol 6000) were the main strategies involved for productive extrusion of MX. Evaluation of MX solid-state (TGA, DSC and PLM), absolute percent crystallinity, in-vitro dissolution (in acidic/aqueous pHs), and stability testing in accelerated conditions up to 6-months as well as a long-term shelf for 36-months were performed. A comparative bioavailability study of selected MX-Pellets was carried-out against the innovator product (Mobic®) in 6 healthy volunteers under fed-conditions. Results TGA, DSC and PLM analyses proved the dispersion of MX in amorphous-state within polymeric matrix by HME. MX/Soluplus pellets exhibited the lowest crystallinity % and best dissolution performance among other polymers in both pHs. In addition, presence of Soluplus safeguards final pellets stability under different storage conditions. MX rate of absorption (Tmax) from Soluplus-based pellets attained a value of 45 min, which was 6-times faster than Mobic® (4.5 hr). Conclusion A promising oral MX formula prepared by HME was successfully developed with a rapid onset of analgesic action (Tmax of 45 mins; almost 2-times faster than reported intramuscular injection), hence appropriate in the early relief of pain associated with rheumatoid arthritis and osteoarthritis. Moreover, the proposed formula was physico-chemically stable up to 36 months of shelf-life storage.
The use of ternary amorphous solid dispersions (ASDs) comprised of surfactants and synthetic polymers to improve the solubility of low water soluble active pharmaceutical ingredients (APIs) have been widely investigated as an emerging concept. Shellac is used as complex resin for coating purposes, but to the best of our knowledge, the use of shellac as natural excipient in ASDs has not been reported. The current study has sought to prepare binary and ternary ASDs of shellac, alone or in combination with HPMC, with the model API loratadine (LOR) via spray drying and hot melt extrusion to achieve solubility improvement and supersaturation maintenance. The ASDs were characterized and tested for their in-vitro dissolution performance. Among various shellac fractions within the ternary ASDs, the 10% weight fraction was found to increase the solubility 30 folds and maintain the supersaturation for 3 h compared to other binary and ternary formulations. This superiority was due to specific and stronger API matrix interactions detected via ATR-IR, which was further studied in terms of stability. It was found that there exists a correlation between the amount of the dissolved API and the API crystallinity, which dictates the level of supersaturation. While the crystallinity is set by the LOR concentration at the end of the test, the dissolution rate depended on the origin of the crystals.
The thermal behavior of carvedilol and loratadine was studied by differential scanning calorimetry (DSC). The glass-forming ability, the tendency for crystallization from the glass (glass stability) and from the metastable and equilibrium melt was investigated by DSC. This technique was also used to characterize the glass transition of carvedilol and loratadine by determining the activation energy of the structural relaxation, the dynamic fragility, and the heat capacity jump associated with the glass transformation. Different aspects of the molecular mobility in carvedilol and loratadine were analyzed by Thermally Stimulated Depolarization Currents (TSDC), while in carvedilol the Dielectric Relaxation Spectroscopy (DRS) technique was also used. Carvedilol stands out for its high values of specific heat jump and dynamic fragility, which has been attributed to the particular mobility of this glass-former in the glass transformation region, a consequence of specific characteristics of its molecular structure. These molecular features are also at the origin of a relaxation above Tg that has been detected and characterized by TSDC; the DRS investigation allowed to better understand the molecular dynamics in carvedilol in the amorphous solid, in the metastable liquid state and in the glass transformation region. Finally, the secondary relaxations in loratadine were studied by TSDC, while those in carvedilol were studied by the two dielectric techniques and the results were compared and discussed.
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Poor bioavailability of ophthalmic drops is mainly due to drainage through the nasal-lacrimal duct and a very low permeability through corneal epithelium. The aim of our study was to prepare and characterize an ocular hydrogel of loratadine, as an example of a lipophilic drug, to increase drug concentration and residence time at the site of action in the eye. In this study, a 2³ full factorial design was employed to design and compare the properties of eight different loratadine containing hydrogel formulations. Results showed a significant correlation between the swelling and porosity ratios of the hydrogels and the Pluronic percentage and Pluronic/ carbomer ratio in the formulations. Moreover, the release profiles showed fast and sustained release of all the formulations. Evaluation of hydrogels structure by the FT-IR technique indicated that Pluronic interacts with hydroxyl and carboxylic groups in carbomer, which is the main reason of the hydrogel network formation and interacts with loratadine.The permeation of loratadine through rabbit cornea showed that drug permeation percentages for the F2 and F7 formulations were 15 and 70 folds more than that of the control. © 2018, Iranian Journal of Pharmaceutical Research. All rights reserved.
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In the present work, the thermal decomposition of glimepiride (sulfonylurea hypoglycemic agent) was studied using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG). Isothermal and non-isothermal methods were employed to determine kinetic data of decomposition process. The physical chemical properties and compatibilities of several commonly used pharmaceutical excipients (glycolate starch, microcrystalline cellulose, stearate, lactose and Plasdone) with glimepiride were evaluated using thermoanalytical methods. The 1:1 physical mixtures of these excipients with glimepiride showed physical interaction of the drug with Mg stearate, lactose and Plasdone. On the other hand, IR results did not evidence any chemical modifications. From isothermal experiments, activation energy (Ea) can be obtained from slope of lnt vs. 1/T at a constant conversion level. The average value of this energy was 123 kJ mol–1. For non-isothermal method Ea can be obtained from plot of logarithms of heating rates, as a function of inverse of temperature, resulting a value of 157 and 150 kJ mol–1, respectively, in air and N2 atmosphere, from the first stage of thermal decomposition.
This work aims the evaluation of the kinetic triplets corresponding to the two successive steps of thermal decomposition of Ti(IV)–ethylenediaminetetraacetate complex. Applying the isoconversional Wall–Flynn–Ozawa method on the DSC curves, average activation energy: E=172.49.7 and 205.312.8 kJ mol–1, and pre-exponential factor: logA=16.380.84 and 18.961.21 min–1 at 95% confidence interval could be obtained, regarding the partial formation of anhydride and subsequent thermal decomposition of uncoordinated carboxylate groups, respectively. From E and logA values, Dollimore and Mlek methods could be applied suggesting PT (Prout–Tompkins) and R3 (contracting volume) as the kinetic model to the partial formation of anhydride and thermal decomposition of the carboxylate groups, respectively.
A new method of obtaining the kinetic parameters from thermogravimetric curves has been proposed. The method is simple and applicable to reactions which can not be analyzed by other methods. The effect of the heating rate on thermogravimetric curves has been elucidated, and the master curve of the experimental curves at different heating rates has been derived. The applications of the method to the pyrolyses of calcium oxalate and nylon 6 have been shown ; the results are in good agreement with the reported values. The applicability of the method to other types of thermal analyses has been discussed, and the method of the conversion of the data to other conditions of temperature change has been suggested. From these discussions, the definition of the thermal stability of materials has been criticized.
Chloroprocaine hydrochloride (2-CPCHC) is a local anaesthetic agent of the ester type preferentially used for epidural anaesthesia. The compound, official in the USP, was found to exist in two polymorphic crystal forms which have been characterized by thermomicroscopy, differential scanning calorimetry (DSC), pycnometry, FTIR-, FT-Raman-spectroscopy as well as X-ray powder diffractometry. Based on these data the relative thermodynamic stability of the two forms was determined and is represented in a semi-schematic energy/temperature diagram. Mod. I° is the thermodynamically stable form at room temperature. This form is present in commercial products and can be crystallized from ethanol. Mod. II can be obtained by annealing the supercooled melt in a temperature range between 100 and 130°C. Upon heating mod. II exhibits an exothermic phase transition (ΔtrsH II-I: -5.0±0.5 kJ mol-1) at about 134°C to mod. I° (melting point 175°C, ΔfusH I: 46.6±0.6 kJ mol-1). The exothermic transformation of mod. II to mod. I° confirms that mod. I° is thermodynamically stable in the entire temperature range (heat of transition rule) whereas mod. II is monotropically related to mod. I°, i.e. is metastable at all temperatures below its melting point. Mod. II is of low kinetic stability at room temperature and the transformation to mod. I° starts within a few minutes at room temperature. The N-H band in the infrared spectrum of mod. I° (3433 cm-1) lies at significantly higher wavenumbers than that of mod. II (3413 cm-1) indicating differences in the hydrogen bonding arrangement. Furthermore, the measured density of mod. I° is lower than the density of mod. II and thus both, the IR- and the density-rule are violated in this polymorphic system.
This work aims the evaluation of the kinetic triplets corresponding to the two successive steps of thermal decomposition of Ti(IV)- ethylenediaminetetraacetate complex. Applying the isoconversional Wall-Flynn-Ozawa method on the DSC curves, average activation energy: E=172.4±9.7 and 205.3±12.8 kJ mol-1, and pre-exponential factor: logA=16.38±0.84 and 18.96±1.21 min -1 at 95% confidence interval could be obtained, regarding the partial formation of anhydride and subsequent thermal decomposition of uncoordinated carboxylate groups, respectively. From E and logA values, Dollimore and Málek methods could be applied suggesting PT (Prout-Tompkins) and R3 (contracting volume) as the kinetic model to the partial formation of anhydride and thermal decomposition of the carboxylate groups, respectively.
Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.
  • C S Cides
  • A A S Araujo
  • M Santos-Filho
  • J R Matos
  • J Therm
C. S. Cides, A. A. S. Araujo, M. Santos-Filho and J. R. Matos, J. Therm. Anal. Cal., 84 (2006) 441.
  • G G Kay
  • A G Harris
G. G. Kay and A. G. Harris, Clin. Expert Allergy, 29 (1999) 147.
  • Bull Ozawa
Ozawa, Bull. Chem. Soc. Jpn., 38 (1965) 1881.