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Theoretical Aspects of Differential Scanning Calorimetry as a Tool for the Studies of Equilibrium Thermodynamics in Pharmaceutical Solid Phase Transitions

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Abstract

Although differential scanning calorimetry (DSC) is a non-equilibrium technique, it has been used to gain energetic information that involves phase equilibria. DSC has been widely used to characterize the equilibrium melting parameters of small organic pharmaceutical compounds. An understanding of how DSC measures an equilibrium event could make for a better interpretation of the results. The aim of this mini-review was to provide a theoretical insight into the DSC measurement to obtain the equilibrium thermodynamics of a phase transition especially the melting process. It was demonstrated that the heat quantity obtained from the DSC thermogram (ΔH) was related to the thermodynamic enthalpy of the phase transition (ΔH P) via: ΔH = ΔH P/(1 + K − 1) where K was the equilibrium constant. In melting, the solid and liquefied phases presumably coexist resulting in a null Gibbs free energy that produces an infinitely larger K. Thus, ΔH could be interpreted as ΔH P. Issues of DSC investigations on melting behavior of crystalline solids including polymorphism, degradation impurity due to heating in situ, and eutectic melting were discussed. In addition, DSC has been a tool for determination of the impurity based on an ideal solution of the melt that is one of the official methods used to establish the reference standard.

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References

  1. Clas S-D, Dalton CR, Hancock BC. Differential scanning calorimetry: applications in drug development. Pharm Sci Technol To. 1999;2:311–20.

    Article  CAS  Google Scholar 

  2. Laye PG. Differential thermal analysis and differential scanning calorimetry. In: Haines PJ, editor. Principles of Thermal Analysis and Calorimetry. Cambridge: The Royal Society of Chemistry; 2002. p. 55–93.

    Chapter  Google Scholar 

  3. Höhne GWH, Hemminger WF, Flemmersheim HJ. Differential scanning calorimetry: an introduction for practitioners. 2nd ed. Berlin: Springer; 2003.

    Book  Google Scholar 

  4. Ozawa T, Kanari K. A theoretical approach to temperature modulated power consumption DSC. J Therm Anal Calorim. 1999;56:691–7.

    Article  CAS  Google Scholar 

  5. Zhuravlev E, Schick C. Fast scanning power compensated differential scanning nano-calorimeter: 2. heat capacity analysis. Thermochim Acta. 2010;505:14–21.

    Article  CAS  Google Scholar 

  6. Agafonova EV, Moshchenskii YV, Tkachenko ML. Determining the thermodynamic melting parameters of sulfamethoxazole, trimethoprim, urea, nicodin, and their double eutectics by differential scanning calorimetry. Russ J Phy Chem. 2013;87:1291–4.

    Article  CAS  Google Scholar 

  7. Reading M, Craig DQM. Principles of differential scanning calorimetry. In: Craig DQM, Reading M, editors. Thermal analysis of pharmaceuticals. Boca Raton: CRC Press; 2006. p. 1–20.

    Google Scholar 

  8. Vyazovkin S. Therm Anal Anal Chem. 2006;78:3875–86.

    Article  CAS  Google Scholar 

  9. Bergthorsson B. Defining the degree of advancement of a reaction. J Chem Educ. 1975;52:274–6.

    Article  Google Scholar 

  10. Claudy P, Vignon JM. Temperature modulated DSC: theoretical interpretation. J Therm Anal Calorim. 2000;60:333–43.

    Article  CAS  Google Scholar 

  11. Mathot VBF. Calorimetry and thermal analysis of polymers. Munchen: Hanser Publishers; 1994.

    Google Scholar 

  12. Kabo GY et al. Thermochemistry of alkyl derivatives of urea. Bacad Sci USSR Ch. 1990;39:662–7.

    Google Scholar 

  13. Martínez F, Gómez A. Thermodynamic study of the solubility of some sulfonamides in octanol, water, and the mutually saturated solvents. J Solution Chem. 2001;30:909–23.

    Article  Google Scholar 

  14. Gana I et al. Benzocain polymorphism: pressure-temperature phase diagram involving forms II and III. Int J Pharm. 2013;456:480–8.

    Article  CAS  PubMed  Google Scholar 

  15. Maddileti D, Swapna B, Nangia A. Tetramorphs of the antibiotic drug trimethoprim: characterization and stability. Cryst Growth Des. 2015;15:1745–56.

    Article  CAS  Google Scholar 

  16. Charsley EL et al. DSC studies on organic melting point temperature standards. Thermochim Acta. 2006;446:29–32.

    Article  CAS  Google Scholar 

  17. Lang P et al. Polymorph screening of an active material. J Pharm Biomed Anal. 2013;84:177–83.

    Article  CAS  PubMed  Google Scholar 

  18. Ford J, Mann TE. Fast-scan DSC and its role in pharmaceutical physical form characterization and selection. Adv Drug Del Rev. 2012;64:422–30.

    Article  CAS  Google Scholar 

  19. Gaisford S, Buanz BM. Pharmaceutical physical form characterization with fast (>200°C min−1) DSC heating rates. J Therm Anal Calorim. 2011;106:221–6.

    Article  CAS  Google Scholar 

  20. Zencirci N et al. Crystal polymorphs of barbital: new about a classic polymorphic system. Mol Pharm. 2014;11:338–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gaisfold S. Fast-scan differential scanning calorimetry. Eur Pharm Rev. 2008;4:83–9.

    Google Scholar 

  22. Gaujac A et al. Investigations into the polymorphic properties of N, N-dimethyltryptamine by X-ray diffraction and differential scanning calorimetry. Microchem J. 2013;110:146–57.

    Article  CAS  Google Scholar 

  23. Toscani S et al. Stability hierarchy between piracetam forms I, II, and III from experimental pressure-temperature diagrams and topological inferences. Int J Pharm. 2016;497:96–105.

    Article  CAS  PubMed  Google Scholar 

  24. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50:47–60.

    Article  CAS  PubMed  Google Scholar 

  25. van Dooren AA, Muller BW. Purity determinations of drugs with differential scanning calorimetry (DSC)—a critical review. Int J Pharm. 1984;20:217–33.

    Article  Google Scholar 

  26. Mathkar S et al. The use of differential scanning calorimetry for the purity verification of pharmaceutical reference standards. J Pharm Biomed. 2009;49:627–31.

    Article  CAS  Google Scholar 

  27. The European Pharmacopoeia 7.0. 2008. http://180.168.103.34:7947/zl/EP7/51200E.PDF. Accessed 7 Jan 2016.

  28. Faroongsarng D, Kadejinda W, Sunthornpit A. Thermal behavior of a pharmaceutical solid acetaminophen doped with p-aminophenol. AAPS Pharm Sci Tech. 2000;1(3):62–8.

    Article  Google Scholar 

  29. Zhang SW et al. Formation enthalpies and polymorphs of nicotinamide-R-mandelic acid co-crystals. Cryst Growth Des. 2012;12:4090–7.

    Article  CAS  Google Scholar 

  30. Wang L et al. Pharmaceutical cocrystals of diflunisal with nicotinamide or isonicotinamide. Org Process Res Dev. 2013;17:1413–8.

    Article  CAS  Google Scholar 

  31. Hiendrawan S et al. Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid. Int J Pharm. 2016;497:106–13.

    Article  CAS  PubMed  Google Scholar 

  32. Wang W, Chen M, Chen G. Issues in freeze drying of aqueous solutions. Chin J Chem Eng. 2012;20:551–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The author would like to thank Dr. Brian Hodgson for the English language revision.

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Correspondence to Damrongsak Faroongsarng.

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Faroongsarng, D. Theoretical Aspects of Differential Scanning Calorimetry as a Tool for the Studies of Equilibrium Thermodynamics in Pharmaceutical Solid Phase Transitions. AAPS PharmSciTech 17, 572–577 (2016). https://doi.org/10.1208/s12249-016-0530-2

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