Abstract
This article focuses on the development of an innovative method, based on thermodynamic considerations and with the use of Differential Scanning Calorimetry (DSC), for the estimation of the melting enthalpy of crystalline compounds which are metastable near their melting temperature. The curves obtained, at various heating rates, are analysed in two steps. In the first step, the area of a zone generated by the melting endothermic peak is calculated following a specific method. In the second step, the melting enthalpy is extracted from this area through an enthalpy balance. This method is applied to both identified crystallographic forms, named form I and form II, respectively, of Etiracetam (UCB Pharma). The results show that the melting enthalpy of the stable form II compare well with the ones obtained using conventional methods. The curves of the metastable form I present thermal instabilities (partial solid–solid polymorphic transition and beta-recrystallization) near the form I melting peak leading to difficulties for a direct determination of the melting enthalpy by conventional methods. The proposed method is therefore very useful for the estimation of the form I melting enthalpy.
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Notes
DSC figures are given in degree celsius. The program used does not allow the conversion to Kelvin.
All initial and final temperature combinations, for each heating rate, are summarised in the Supporting information (SI, Tables S2, S3, S4 and S5).
These results are given in the Supporting information (SI, Figs. S5 and S6).
All initial and final temperatures combination, for each of the heating rates, are summarised in the Supporting information (SI, Tables S6, S7 and S8).
A zoom of each sub-figure of Fig. 11 is given in the Supporting information (SI, Fig. S7).
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Acknowledgements
Christelle Herman acknowledges technical support from UCB Pharma, based in Braine l’Alleud (Brussels), Belgium, and financial support from the Fonds National de la Recherche Scientifique (F.R.S.-F.N.R.S.), Belgium.
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Herman, C., Leyssens, T., Vermylen, V. et al. A new approach for the estimation of the melting enthalpy of metastable crystalline compounds using differential scanning calorimetry. J Therm Anal Calorim 107, 777–788 (2012). https://doi.org/10.1007/s10973-011-1555-0
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DOI: https://doi.org/10.1007/s10973-011-1555-0