Thermodynamic relationship between flupirtine maleate polymorphs
Flupirtine maleate (FPTM) is usually formed from a mixture of two crystal forms A and B, of which form A has very complicated thermal properties. Our goal in this study was to separate overlapping thermal events, provide insights into the thermal properties of FPTM, and finally to evaluate the thermodynamic relationships between the two forms. In this study, conventional and modulated differential scanning calorimetry (DSC, MDSC), thermogravimetry, and X-ray powder diffraction (XRPD) were used to study the thermal properties and thermodynamic relationships of FPTM polymorphs. In particular, MDSC is an effective tool for thoroughly characterizing the thermal behavior of compounds by deconvoluting overlapping melting and decomposition processes. The MDSC revealed that the melting processes of both forms occurred simultaneously with their decomposition. In addition, performing DSC at different annealing temperatures and XRPD indicated that form A begins to transform to B at 146 °C. These results helped us evaluate the relative stability of both polymorphs through the construction of an energy versus temperature diagram. According to this E/T diagram, the two forms are enantiotropically related. Moreover, form A is the more stable form below the transition temperature (Tt).
KeywordsThermodynamic relationships Flupirtine maleate Polymorphism MDSC E/T diagram
The authors would like to acknowledge the contributions of the following people: YuanjunLiang, Hongde Pharmacetical Co., Beijing for supplying the sample. We also wish to thank Edmund F. and Rhoda E. Perozzi for very extensive content and grammar editing.
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