On the dehydration enthalpies of some beta-aluminas

The energetics of the dehydration reaction of single crystal (Na, Na 50%-Li, Li) and ceramic Na beta-aluminas have been studied.From the dependence of the dehydration enthalpy values on the water content it has been deduced that lattice water can be bound in two different ways i.e. by ion-dipole interactions with conducting cations and by hydrogen bonds with spinel block oxygens. As expected, the first one gives binding energies depending on the nature of the monovalent cation (H=84.5 and 59.4 kJ/mol H₂O for Li and Na beta-alumina respectively). In contrast, the enthalpy change associated with the second one is identical for the three beta-aluminas (H=15.1 kJ/mol H₂O). The ceramic Na beta-alumina undergoes a surface reaction too (with CO₂) leading to the formation of carbonates and bicarbonates.

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Zusammenfassung Die Energetik der Dehydratisierungsreaktion von Einkristallen von Na-, Na (50%)/Li- und Li- sowie von Na--Aluminiumoxid wurde untersucht. Aus der Abhängigkeit der Dehydratisierungsenthalpie vom Wassergehalt ergibt sich, daß Wasser auf zwei verschiedene Weisen gebunden ist, nämlich durch Ion-Dipol-Wechselwirkung mit leitenden Kationen und durch Wasserstoffbrückenbindungen mit Sauerstoffatomen. Wie zu erwarten war werden für die ersteren von der Natur der einwertigen Kationen abhängige Bindungsenergien (H=84.1 kJ/Mol H₂O bzw. 59.4 kJ/Mol H₂O für Li- bzw. Na--Alumina) erhalten. Die auf die zweite Wechselwirkung zurückzuführenden Enthalpieänderung ist dagegen für die drei-Aluminiumoxide identisch (H=15.1 kJ/Mol H₂O). Das keramische Na--Aluminiumoxid zeigt auch eine Oberflächenreaktion mit CO₂, die zur Bildung von Carbonaten und Bicarbonaten führt.

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(Na, Na 50%-Li, Li)- -- . , - . , Li — Na-- , , 84.5 59.4 / ₂. , - 15.1 / ₂. Na- , .

     

Thermal analysis of a drug-polymeric excipient solid system

Differential scanning calorimetry has been applied to the study of the solid system cross-linked polyvinylpyrrolidone/trimethoprim.Different results have been systematically obtained on co-ground and not co-ground mixtures, suggesting some type of interaction to take place between components as a consequence of co-grinding.A simple phenomenological model of the interaction is proposed, which quite satisfactorily agrees with thermal data.

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Zusammenfassung Das feste System von vernetztem Polyvinyl-pyrolidin/Trimethoprim wurde mittels DSC untersucht. Unterschiedliche Ergebnisse wurden systematisch für zusammen und nicht zusammen verriebene Mischungen gefunden, was auf eine Wechselwirkung zwischen Komponenten beim Verreiben hindeutet. Ein einfaches phänomenologisches Modell dieser Wechselwirkung wird vorgeschlagen, das mit thermischen Daten befriedigend übereinstimmt.

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This work has been partially supported by Ministero Pubblica Istruzione (Fondi 60%).     

Probenecid and benzamide: DSC applied to the study of an “impossible” pharmaceutical system

Journal of Thermal Analysis and Calorimetry - The study of the binary system probenecid–benzamide is an excellent example of the power and the limits of thermal analysis applied to the...     

The Physico-Chemical Properties of Glipizide: New Findings

The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.     

Quantification methods of amorphous/crystalline fractions in high-energy ball milled pharmaceutical products

In this work, thermoanalytical, diffractometry, and microscopy measurements have been performed in order to characterize the effect of high energy milling on a drug active in the migraine prophylaxis and smoke cessation. We can assert that the mechanical treatment induces only a partial amorphisation of the solid phase, in particular it reduces the crystal order by producing lattice defects which propagate from the surface to the bulk crystal. For this reason, the DSC is able to detect the presence of ordered solid, while the powder X-ray diffractometry, because of its low penetration depth, does not reach the crystalline core of the particles.     

On the quantitative reliability of heat flux DSC

In an attempt to explain how the calibration factor of a heat flux DSC cell depends both on the standard utilized and on the experimental variables, a study has been undertaken of the entire DSC trace.This report deals with the second half of the peak and shows that, other experimental conditons being fixed, the peak area increases with increasing heating rate.This accounts for the observed decrease in the calibration factors with increasing heating rate.

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Zusammenfassung Die gesamte DSC-Kurve wurde untersucht, um zu klären, wie der Eichfaktor einer Wärmefluss-DSC vom verwendeten Eichstandard und von den Versuchsbedingungen abhängt. Der vorliegende Teil behandelt den zweiten Abschnitt eines DSC-peaks (vom Maximum an). Es wird gezeigt, dass bei Konstanthalten aller anderen Versuchsbedingungen die peak-Flächen mit steigender Aufheizgeschwindigkeit zunehmen. Das wird als Ursache für die beobachtete Verringerung des Eichfaktors mit steigender Aufheizgeschwindigkeit angesehen.

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Thermal Decomposition and Melting of A New Carboxyindole Derivative

GV150526A is a novel 2-carboxyindole derivative, recently synthesized by GlaxoWellcome, which is used in treatment or prevention of CNS disorders resulting from neurotoxic damage. It has been prepared in three forms, F1, F2 and F3, having significantly different hydration/dehydration behavior and/or diffraction patterns. Here, we extend the thermal analysis of these polymorphs above 200°C, where all forms are fully dehydrated and the main thermal phenomena are decomposition and melting. Simultaneous TG/DSC measurements have been repeated in wet and dry nitrogen atmospheres over a wide range of heating rates. Form F3 displays a qualitatively different behavior relative to F1 and F2. This fact is interpreted as an evidence of a mechanism of decomposition which sets F3 apart from F1 andF2. The thermal data are summarized by simple heuristic equations and few ‘apparent’enthalpies. This revised version was published online in August 2006 with corrections to the Cover Date.     

Quantification of drug amorphous fraction by DSC

The processes of production of drugs and dosage forms in the solid state often cause unwanted transformation of portions of the substances into amorphous state, with significant changes of properties such as stability and bio-availability. When this amorphous fraction is of the order of a few percent, it usually goes unnoticed, but it should be accurately determined within a quality control system. In this work, we consider a model drug, perphenazine, where partial amorphisation may be induced by standard mechanical treatments. We show that Differential Scanning Calorimetry (DSC) leads to consistent estimations of the amorphous fractions induced by the treatment. Furthermore, DSC also yields the expected amounts of amorphous perphenazine when analysing known mixtures of perfectly crystalline samples (untreated) and partially amorphous samples (treated). We show that even amorphous fractions of the order of 1% are accurately estimated by our method.