Physico-chemical solid-state characterization of pharmaceutical pyrazolones: An unexpected thermal behaviour

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Abstract

In this work, the thermal behaviour of three active substances (phenazone, aminophenazone, phenylbutazone) was studied by drawing up the TG/DTG/DTA curves in air/nitrogen atmosphere at 10 °C min−1 heating rate. The information on the thermal-induced events was corroborated with the IR spectra of the solid samples (pharmaceutical compounds and the remaining chars after heating treatment), respectively with the ones obtained by evolved gases analysis (EGA).

The data on a possible drug–excipient interaction were obtained from the thermoanalytical study of mixtures of these active compounds with talc, magnesium stearate, starch and microcrystalline cellulose. No changes were observed by TG/DTG/DTA curves of mixtures in comparison with the pure compound.

Even if the three active substances contain the same heterocyclic ring, having similar molecular structures, their thermal behaviour is not similar. According to thermal and evolved gas analysis, it was proved that formation of CO2 does not involve atmospheric oxygen. By stoichiometric means, the molecular breakdown of aminophenazone can generate only carbon monoxide, which undergoes disproportionation, generating CO2.

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