Journal of Thermal Analysis and Calorimetry

, Volume 134, Issue 3, pp 2057–2063 | Cite as

Thermodynamic relationship between flupirtine maleate polymorphs

  • Yumei ZhaoEmail author
  • Zhi-bing ZhengEmail author
  • Song Li


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).


Thermodynamic 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.


  1. 1.
    Rabel SR, Jona JA, Maurin MB. Applications of modulated differential scanning calorimetry in preformulation studies. J Pharm Biomed Anal. 1999;21:339–45.CrossRefGoogle Scholar
  2. 2.
    Gill P, Sauerbrunn S, Reading M. Modulated differential scanning calorimetry. J Therm Anal Calorim. 1993;40:931–9.CrossRefGoogle Scholar
  3. 3.
    Kannan V, Brahadeeswaran S. Synthesis, growth, thermal, optical and mechanical studies on 2-amino-6-methylpyridinium 4-hydroxybenzoate. J Therm Anal Calorim. 2016;124:889–98.CrossRefGoogle Scholar
  4. 4.
    Kumar L, Baheti A, Bansal AK. Effect of a counterion on the glass transition temperature (T g) during lyophilisation of ganciclovir salt forms. Mol Pharm. 2010;8:309–14.CrossRefGoogle Scholar
  5. 5.
    Górska A, Szulc K, Ostrowska-Ligęza E, Bryś J, Wirkowska-Wojdyła M. Effect of composition and drying method on glass transition temperature, water sorption characteristics and surface morphology of newly designed β-lactoglobulin/retinyl palmitate/disaccharides systems. J Therm Anal Calorim. 2017;130:177–85.CrossRefGoogle Scholar
  6. 6.
    Aubuchon SR, Thomas LC, Theuerl W, Renner H. Investigations of the sub-ambient transitions in frozen sucrose by modulated differential scanning calorimetry (MDSC®). J Therm Anal Calorim. 1998;52:53–64.CrossRefGoogle Scholar
  7. 7.
    Qiu S, Chu H, Zou Y, Xiang C, Zhang H, Sun L, Xu F. Themochemical studies of rhodamine B and rhodamine 6G by modulated differential scanning calorimetry and thermogravimetric analysis. J Therm Anal Calorim. 2016;123:1611–8.CrossRefGoogle Scholar
  8. 8.
    Rijeka AD, Zagreb MD, et al. US patent 2011/0184030 Al.Google Scholar
  9. 9.
    Landgraf KF, Olbrich A, Pauluhn S, Emig P, Kutscher B, Stange H. Polymorphism and desolvation of flupirtine maleate. Eur J Pharm Biopharm. 1998;46:329–37.CrossRefGoogle Scholar
  10. 10.
    Grunenberg A, Henck JO, Siesler HW. Theoretical derivation and practical application of energy/temperature diagrams as an instrument in preformulation studies of polymorphic drug substances. Int J Pharm. 1996;129:147–58.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  1. 1.Laboratory of Computer-Aided Drug Design and DiscoveryBeijing Institute of Pharmacology and ToxicologyBeijingChina
  2. 2.Laboratory of Toxicant AnalysisBeijing Institute of Pharmacology and ToxicologyBeijingChina
  3. 3.State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina

Personalised recommendations