Thermal stability of pentoxifylline: active substance and tablets

Thermal analysis is a routine method in the solution of pharmaceuticals problems such as the control of raw materials, to the determination of purity, to the qualitative and quantitative analysis of drug formulation, tests of thermal stability and compatibility, the determination of kinetic parameters, etc. The evaluation of thermal stability in the solid state is mostly made by analyzing their decomposition under isothermal and non-isothermal conditions. The present work reports the study on the thermal behavior of pentoxifylline—active substance and tablets, respectively, the determination of the kinetic parameters for the decomposition process under non-isothermal conditions and in a nitrogen atmosphere at five heating rates: 2.5, 5, 7.5, 10 and 15 °C min^?1. For the determination of kinetic parameters from the TG/DTG curves, the following differential methods were utilized: Friedman isoconversional and Chang, respectively, integral methods: Flynn–Wall–Ozawa, Kissinger–Akahira–Sunose, Li–Tang, and Starink. Thermoanalytical curves showed that the active substance is thermally more stable than the tablets. The decrease in stability was attributed to the presence of excipients.     

Thermal stability of metronidazole drug and tablets

TG and DSC data were used to determine the thermal parameters of metronidazole drug and tablets. Three tablets A, B and C were analysed. The TG curves of metronidazole drug and tablets A and B displayed five and C four thermal decomposition processes, respectively. Analysis of the DSC data pointed to chemical interactions between metronidazole drug and the excipients of tablets, suggested by alterations in the melting point of metronidazole. The rate constants obtained from the isothermal TG data presents following sequence of the thermal stability: tablet A>tablet C>metronidazole drug>tablet B. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thermal behaviour of melamine

Melamine undergoes condensation on heating with elimination of ammonia and formation of insoluble products. Thermogravimetry and infrared characterisation show that two products of successive condensation can be reproducibly obtained upon heating atT}<500 °C and then at 600 °C. Above 620 °C, the melamine condensate undergoes thermal degradation with quantitative formation of volatile products.

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Zusammenfassung Melanin geht beim Erhitzen eine Kondensation unter Abgabe von Ammoniak und Bildung unlöslicher Produkte ein. Durch Thermogravimetrie und Infrarotspektroskopie wird gezeigt, daß beim Erhitzen zwei Produkte von aufeinanderfolgenden Kondensationsreaktionen beiT}<500 °C undT= 600 °C reproduzierbar erhalten werden. Oberhalb 620 °C wird das Melaminkondensat vollständig unter Bildung flüchtiger Produkte thermisch zersetzt.

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. , . , 500°, — 600°. 620° .

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The authors wish to thank Dr. N. Del Fanti of Mantefluos, Italy for most helpful discussion.

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This work has been supported by the Consiglio Nazionale delle Ricerche through the Progetto Finalizzato Chimica Fine e Secondaria.     

Thermal behaviour of riboflavin

From the thermal decomposition curves of riboflavin at various heating rates in static air atmosphere, the stages of thermal decomposition of this compound were established. The following kinetic parameters were calculated for the first decomposition stage of this process: activation energy (E _a ), reaction order (n), preexponential factor (A) and reaction rate constant (k). A mechanism of the changes is proposed.

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Zusammenfassung Die Stadien der thermischen Zersetzung von Riboflavin wurden aus den Kurven der thermischen Zersetzung in Luftatmosphäre bei verschiedenen Aufheizgeschwindigkeiten ermittelt. Für den ersten Zersetzungsschritt dieses Prozesses werden die Werte für die Aktivierungsenergie (E _a ), die Reaktionsordnung (n), den präexponentiellen Faktor (A) und die Reaktionsgeschwindigkeitskonstante (k) berechnet. Für die Umwandlungen wird ein Mechanismus vorgeschlagen.

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, , . , (E _a ), (n), (A) (k). .

     

Thermal behaviour of some minerals

Thermal behaviour of some minerals (kaolinite, halloysite, two montmorillonites, quartz and calcite) for different sample amounts and heating rates has been investigated using differential thermal analysis. On the basis of the DTA analysis carried out, the PA curves of each mineral have been obtained for different heating rates. These diagrams can be employed in the semiquantitative evaluation of identical substances contained in uncharacterized polymineral samples.     

Thermal behaviour of cardanol-based benzoxazines

A novel benzoxazine monomer (Bz-C) based on agrochemical renewable resource—cardanol (by-product of cashew nut tree, Anacardium occidentale) was synthesized. Bz-C, a liquid monomer, was used as reactive diluent for the solventless synthesis of bisphenol-A benzoxazine monomer (Bz-A). Benzoxazine monomer based on cardanol and bisphenol-A in 3:1, 1:1 and 1:3 blend ratio were prepared by this method. The resins had Brookfield viscosity at 316 K in the range of 145–81,533 mPa s. The resins were characterized by ¹H-NMR, FTIR and elemental analysis. Curing characteristics were studied by DSC analysis. Thermal stability of cured resins was found to improve with increase in Bz-C content in the blends.     

Thermal behaviour of thallous perchlorate

Thermal decomposition characteristics of thallous perchlorate are investigated in nitrogen and in air using TG and DTA techniques. Isothermal studies at 380°, 400°, 420° and 440° in air and in nitrogen showed that the relative amounts of the decomposition products, namely, thallic oxide and thallous chloride, depend upon both the temperature and the atmosphere around the sample. At low pressures (5×10^–1 mm/Hg) there is volatilization of thallous perchlorate even at 200°.

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Zusammenfassung Die thermischen Zersetzungscharakteristika von Thallium(I)-perchlorate wurden in Stickstoff und in Luft unter Anwendung der TG- und DTA-Techniken untersucht. Isotherme Studien bei 380°, 400°, 420° und 440° in Luft und in Stickstoff zeigten, daß die relativen Mengen der Zersetzungsprodukte, Thallium(III)oxid und Thallium(I) Chlorid, sowohl von der Temperatur als auch von der das Muster umgebenden Atmosphäre abhängen. Bei niedrigen Drücken (5×10^–1 mm/Hg) verflüchtigt sich Thallium(I)perchlorat bei 200°.

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Résumé On a étudié par TG et ATD les caractéristiques de la décomposition thermique du perchlorate de thallium(I) dans l'azote et dans l'air. Des études isothermes à 380, 400, 420 et 440°C dans l'air et dans l'azote ont montré que les taux relatifs de produits de décomposition, c'est-à-dire l'oxyde de thallium(III) et le chlorure de thallium(I), dépendent de la température ainsi que de l'atmosphère autour de l'échantillon. Sous faible pression (5 · 10^–1 torr) le perchlorure de thallium(I) se volatilise même à 200°.

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. , 380°, 400°, 420°, 440° , , , , , . (5 · 10^–1 . .) 200°.

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One of us (A.S.G.) is thankful to the Council of Scientific and Industrial Research, India for the award of a fellowship.     

Thermal behaviour of zinc phenoxyacetate

The thermal behaviour of solid zinc phenoxyacetate was investigated by DSC and TG techniques. The results obtained showed that this compound is a dihydrate and that the water molecules are differently bonded. The compound melts and then decomposes in two steps, with the formation of ZnCO₃ and ZnO, respectively. The thermodynamic parameters associated with the thermal processes were evaluated.

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Zusammenfassung Mittels DSC und TG wurde das thermische Verhalten von festem Zinkphenoxyazetat untersucht. Die Ergebnisse zeigen, daß diese Verbindung ein Dihydrat ist, in dem die beiden Wassermoleküle unterschiedlich gebunden sind. Die Verbindung schmilzt und zersetzt sich anschließend unter der Bildung von ZnCO₃ und ZnO in zwei Schritten. Die thermodynamischen Parameter der thermischen Prozesse wurden bestimmt.

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. , . , , . .

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We thank the Italian Public Education Minister for financial support.     

Thermal behaviour of polyacrylamidoxime-copper chelates

The purpose of this work was to investigate the effect of several factors (anion type in the copper salt, pH and concentration of the salt solution) on the structure and thermo-oxidative degradation of the polyacrylamidoxime-copper chelates, by using elemental analysis, IR spectroscopy and dynamic thermogravimetry. The chelates containing copper ions as sulphate exhibit a better initial thermal stability than the polyacrylamidoxime fibre presumably due to the crosslinking generated by the intermolecular complexation of the ions; the removal of the sulphate anions takes place concomitantly with the second step of polymeric chain decomposition. The initial thermal decomposition of the chelates formed by copper ions as nitrate begins at lower temperatures as compared to the polyacrylamidoxime fibre, probably by the nitrate anion release, which partly overlaps the initial decomposition of the copper ion-crosslinked polymeric chains. Copper ions as either sulphate or nitrate catalyse the reactions involved in the main step of polyacrylamidoxime fibre decomposition; the higher the copper amount, the stronger the catalytic effect.     

Thermal behaviour of lyocell fibres

Fourier-transform infrared (FTIR) spectroscopy has been applied in combination with wide-angle X-ray diffraction and measurements of strength, fluidity, yellowness, birefringence, and moisture regain to detect microstructural changes in lyocell fibres, a regenerated cellulose fibre, subjected to direct heat and annealing treatments. TMA, and SEM were used to show the effect of direct heat and annealing on lyocell fibres. The FTIR spectroscopy results show that a decrease in intermolecular hydrogen bonding occurs at 70 and 80 °C for annealed and directly heated samples, respectively. The results demonstrate increase of the intensity of O–H stretching vibrations, this associated with hydrogen bonds reforming around 130 °C. Lyocell fibres shrink with direct heating in the temperature range 130–160 °C. The crystallinity decreases gradually with increasing temperature. There is no significant change in colour of the samples annealed up to 150 °C. A continuous increase in the fluidity occurs for the annealed samples in the range 150–230 °C. The tenacity and breaking extension of heated samples decrease with increasing temperature. The lower annealing temperatures cause no observable change in the smooth and void-free surface, but in the annealing temperature range 170–230 °C, substantial non-uniformity is apparent on the surface of the fibres.     

Thermal behaviour of modified faujasites

A derivatograph was used to follow the modification of the skeleton structure and thermal stability of zeolites in sodium and ammonium forms. Analogous investigations were carried out by independent methods such as IR and X-ray. Comparison showed good agreement between the results. The controlled dealumination of the Y-type zeolite enhanced the thermal stability     

Near-infrared determination of active substance content in intact low-dosage tablets

Near-infrared (NIR) spectroscopy can be applied to determine the active substance content of tablets. Its great advantage lies in the minimal sample preparation required, which helps to reduce the potential for error. The aim of this study is to show the feasibility of this method on low-dosage tablets. The influence of various spectral pretreatments [standard normal variate (SNV), multiplicative scatter correction (MSC), second derivative (D2), orthogonal signal correction (OSC), separately and combined] and regression methods on prediction error are compared. Partial least square (PLS) regression provided better prediction than principal component regression (PCR). SNV was applied to the first data set and SNV and a second derivative to the second set to maximise model accuracy for quantifying the active substance of intact pharmaceutical products using diffuse reflectance NIR. The models yielded standard errors of prediction (SEP) of 0.1768 and 0.0682 mg for the two products. The experiments were conducted with two low-dosage pharmaceutical forms and results of NIR predictions were comparable to currently approved methods. Diffuse reflectance NIR has the potential to become a reliable and robust quality control method for determining active tablet content.     

Thermal behaviour of urea nitrate

The thermal decomposition under argon of the boracites M₃B₇O₁₃X (M=divalent metal ion, X=halogen ion or OH^?) has been studied by thermogravimetry (TG) and differential thermal analysis (DTA) for the compositions MgCl, MgOH, CrC1, CrBr, CrI, MnCl, MnBr, MnI, FeCl, FeBr, FeI, CoCl, CoBr, CoI, NiCl, NiBr, NiI, CuCl, CuBr, ZnCl, ZnBr, ZnI, CdCl, CdBr and CdI. The lithium boracites Li₄B ₇O₁₂X, with XCl and Br, have also been studied. The stability of the boracites systematically decreases in the order MCI>MBr>MI. The most stable boracite is CrCl (1% weight loss at 1242°C) and the least stable one studied here is MgOH (1% weight loss at 717°C).     

Thermal behaviour of ground vermiculite

Thermal behaviour of natural vermiculite (Santa Olalla, Huelva, Spain) was investigated by TG, DTA, emanation thermal analysis (ETA) and high temperature XRD on heating in the temperature range from 30 to 1100°C before and after vibratory mill grinding. Microstructure changes of natural and ground vermiculite samples were characterized by using ETA under in situ conditions of heating. By comparing the ETA and XRD results it was demonstrated that a decrease of radon release rate measured by ETA characterized the decrease in the interlayer spacing of the vermiculite samples that followed the dehydration. Dedicated to the memory of Professor Dr. Ferenc Paulik who passed away on October 12, 2005.     

Thermal behaviour studies of procaine and benzocaine

The analysed substances, procaine and benzocaine, are two anaesthetic agents currently being administered in tablet form, also in the topical (cream, gel, balm) and injectable dosage forms. The TG/DTG/DTA curves were obtained in air at different heating rates. For determination of the heat effects, the DTA curves (in μV) were changed with the heat flow curves (in mW), so that the peak area corresponds to an energy in J g^?1 or kJ mol^?1. The non-isothermal experiments are preformed to investigate the thermal degradation process of these active substances, both as a solid and are performed in a dynamic atmosphere of air at different heating rates, by heating from room temperature to 500 °C. The kinetic analysis was performed using the TG data in air for the first step of substance’s decomposition at four heating rates: 7, 10, 12 and 15 °C min^?1. The data were processed according to an appropriate strategy to the following kinetic methods: Kissinger–Akahira–Sunose, Flynn–Wall–Ozawa, Friedman and NPK, to obtain realistic kinetic parameters, even if the decomposition process is a complex one. Thermal analysis was supplemented using Fourier Transform infrared spectroscopy coupled with the TG device to identify the anaesthetics with any products which may have formed (EGA—the evolved gas analysis).     

Thermal behaviour and thermochemistry of ethanaminium iodides

Dynamic thermoanalytical methods (DTA, TG, DTG) have been applied to the investigation of the thermal features of compounds of general formula (Et_nNH_4–n)I, withn=0–4. The primary decomposition step of these derivatives is accompanied by the release of amine and HI to the gaseous phase. The enthalpies of this process have been evaluated on the basis of the van't Hoff equation and analytical TG curves. Values thus derived together with the available literature data were used to estimate the enthalpies of formation and the energies of the crystal lattice of the compounds. Further information regarding this latter quantity was also drawn from the Kapustinskii-Yatsimirskii formula.

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Zusammenfassung Unter Anwendung dynamischer thermoanalytischer Methoden (DTA, TG, DTG) wurden die thermischen Eigenschaften von Verbindungen der allgemeinen Formel (Et_nNH₄–n)I mitn=0–4 untersucht. Im ersten Schritt der Zersetzung werden Amin und HI freigesetzt und gehen in die Gasphase über. Die Enthalpien dieses Prozesses wurden auf der Grundlage der Van't Hoffschen Gleichung und analytischer TG-Kurven ermittelt. Experimentell ermittelte Werte sowie zugängliche Literaturangaben wurden benutzt, um die Bildungsenthalpie und die Kristallgitterenergie dieser Verbindung zu schätzen. Weitere Informationen bezüglich letzterer Größe wurden auch über die Kapustinskij-Yatsimirskij-Formel erhalten.

     

Thermal behaviour of polyetherimide peek blends

PEEK is characterised by high impact and fatigue resistance andT _g of 145C. Blends of PEEK and PEI have been made and scanning electron micro-graphs of the broken specimen show that the two polymers are completely miscible in all proportions. The study also shows that PEEKPEI 5050 blend, can be used as matrix for composite applications with appreciable enhancement ofT _g to 177C.