Skip to main content

Advertisement

SpringerLink
Log in

Preparation and thermodynamic properties of Felodipine form IV

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

Form IV of the calcium channel blocker, Felodipine was obtained consistently via solvent evaporation in a pH-controlled solution, and followed by large-scale crystallization through seeding the saturated solution of Felodipine. Comparing with form I, the crystal form used in the marketed products, form IV has higher melting temperature but lower melting enthalpy. Hence, according to the heat of fusion rule, polymorphs I and IV should be in an enantiotropic relationship. Form I is thermodynamically more stable than form IV at room temperature. Their theoretical polymorphic transformation temperature was estimated at 87.6 °C, which was also confirmed by the solvent-mediated polymorphic transformation experiments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Desiraju GR. Polymorphism: the same and not quite the same. Cryst Growth Des. 2008;8:3–5.

    Article  CAS  Google Scholar 

  2. Láng P, Kiss V, Ambrus R, Farkas G, Szabó-Révész P, Aigner Z, Várkonyi E. Polymorph screening of an active material. J Pharm Biomed Anal. 2013;84:177–83.

    Article  Google Scholar 

  3. Elguero J. Polymorphism and desmotropy in heterocyclic crystal structures. Cryst Growth Des. 2011;11:4731–8.

    Article  CAS  Google Scholar 

  4. Haleblian J, McCrone W. Pharmaceutical applications of polymorphism. J Pharm Sci. 1969;58:911–29.

    Article  CAS  Google Scholar 

  5. Aaltonen J, Allesø M, Mirza S, Koradia V, Gordon KC, Rantanen J. Solid form screening–a review. Eur J Pharm Biopharm. 2009;71:23–37.

    Article  CAS  Google Scholar 

  6. Perlovich GL, Blokhina SV, Manin NG, Volkova TV, Tkachev VV. Polymorphs and solvates of felodipine: analysis of crystal structures and thermodynamic aspects of sublimation and solubility processes. CrystEngComm. 2012;14:8577–88.

    Article  CAS  Google Scholar 

  7. Lu J, Rohani S. Polymorphism and crystallization of active pharmaceutical ingredients (APIs). Curr Med Chem. 2009;16:884–905.

    Article  CAS  Google Scholar 

  8. Cabri W, Ghetti P, Pozzi G, Alpegiani M. Polymorphisms and patent, market, and legal battles: cefdinir case study. Org Process Res Dev. 2007;11:64–72.

    Article  CAS  Google Scholar 

  9. Nussinovitch N, Carroll J, Shamiss A, Grossman E, Katz A, Rachima C, Rosenthal T. Felodipine in the treatment of severe refractory hypertension. J Hum Hypertens. 1996;10:S165–7.

    Google Scholar 

  10. Srčič S, Kerč J, Urleb U, Zupančič I, Lahajnar G, Kofler B, Šmid-Korbar J. Investigation of Felodipine polymorphism and its glassy state. Int J Pharm. 1992;87:1–10.

    Article  Google Scholar 

  11. Lou B, Boström D, Velaga SP. Polymorph control of Felodipine form II in an attempted cocrystallization. Cryst Growth Des. 2009;9:1254–7.

    Article  CAS  Google Scholar 

  12. Surov AO, Solanko KA, Bond AD, Perlovich GL, Bauer-Brandl A. Crystallization and polymorphism of Felodipine. Cryst Growth Des. 2012;12:4022–30.

    Article  CAS  Google Scholar 

  13. Crystal data for Felodipine form IV: C18H19Cl2NO4, formula weight = 384.24, monoclinic, space group P 21/n, a = 11.2433 (7) Å, b = 12.6209 (9) Å, c = 13.5826 (9) Å, β (deg) = 107.774(7), V = 1835.4 (2) Å3, Z = 4, Mo Kα radiation, λ = 0.71073 Å, T = 223 (2) K, 7551 reflections collected, 3421 unique. Final GooF = 1.041, R1 = 0.0988, wR2 = 0.2681. The crystal data are in line with previous report (CCDC: 864027).

  14. Konno H, Taylor LS. Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci. 2006;95:2692–705.

    Article  CAS  Google Scholar 

  15. Song YJ, Wang LY, Yang P, Wenslow Jr RM, Tan B, Zhang HL, Deng ZW. Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion. J Pharm Sci. 2013;102:1915–23.

  16. Fossheim R. Crystal structure of the dihydropyridine Ca2+ antagonist felodipine. Dihydropyridine binding prerequisites assessed from crystallographic data. J Med Chem. 1986;29:305–7.

    Article  CAS  Google Scholar 

  17. Chadha R, Arora P, Garg M, Bhandari S, Jain DS. Thermoanalytical and spectroscopic studies on different crystal forms of nevirapine. J Therm Anal Calorim. 2013;111:2133–42.

    Article  CAS  Google Scholar 

  18. Terada K, Kurobe H, Ito M, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H. Polymorphic and pseudomorphic transformation behavior of acyclovir based on thermodynamics and crystallography. J Therm Anal Calorim. 2013;113:1261–7.

    Article  CAS  Google Scholar 

  19. Chickos JS, Acree WE. Enthalpies of vaporization of organic and organometallic compounds, 1880–2002. J Phys Chem Ref Data. 2003;32:519–878.

    Article  CAS  Google Scholar 

  20. Burger A, Ramberger R. On the polymorphism of pharmaceuticals and other molecular crystals. I. Mikrochim Acta. 1979;72:259–71.

    Article  Google Scholar 

  21. Bauer-Brandl A, Marti E, Geoffroy A, Poso A, Suurkuusk J, Wappler E, Bauer KH. Comparison of experimental methods and theoretical calculations on crystal energies of ‘isoenergetic’ polymorphs of Cimetidine. J Therm Anal Calorim. 1999;57:7–22.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 21205129) and Jiangsu Provincial Fund for Natural Sciences (No. BK2012191).

Author information

Authors and Affiliations

  1. College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, People’s Republic of China

    Lin Wang & Ping Yang

  2. Division of Nanobionics, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of Sciences, Suzhou, 215123, People’s Republic of China

    Lin Wang, Yuejun Song, Bo Tan, Hailu Zhang & Zongwu Deng

Authors
  1. Lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuejun Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hailu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zongwu Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ping Yang or Hailu Zhang.

Supporting Information

10973_2014_4083_MOESM1_ESM.doc

13C solid state NMR spectra and TGA curves of Felodipine form I&IV, comparison of the experimental and theoretical powder XRD patterns of Form IV after Rietveld refinement, and DSC curve of Felodipine form I at a heating rate of 1.0 °C min−1. (DOC 1261 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Song, Y., Yang, P. et al. Preparation and thermodynamic properties of Felodipine form IV. J Therm Anal Calorim 120, 947–951 (2015). https://doi.org/10.1007/s10973-014-4083-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-014-4083-x

Keywords

Search

Navigation