Thermal degradation mechanism for citalopram and escitalopram

  • B. V. Pinto
  • A. P. G. Ferreira
  • E. T. G. Cavalheiro
Article
  • 20 Downloads

Abstract

Citalopram, [(R,S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile] hydrobromide and its S-isomer, escitalopram oxalate, were analyzed regarding thermal degradation by TG/DTG–DTA, DSC, hot-stage microscopy and coupled TG-FTIR techniques. Citalopram presented a decomposition in a single step after melting at 189.3 °C (ΔHfus= 94.4 J g−1), without evidences of crystallization on cooling. Thermal techniques results combined with those from evolved gas analysis suggested decomposition via HBr, dimethylamine and fluorobenzene. Escitalopram presented a thermal degradation that started with the decomposition of the counter ion, after melting at 158.3 °C (ΔHfus= 106.2 J g−1), without evidences of crystallization on cooling followed by the release of dimethylamine and fluorobenzene. GC–MS of the residues confirmed the observations from the thermal analysis, but revealed several intermediates in the degradation of the racemate, probably due to the mixture of isomers. Differences in thermal behavior were attributed to differences in structure and counter ions. A tentative mechanism for their thermal behavior is proposed in both cases.

Keywords

Citalopram Escitalopram Thermal degradation mechanism FTIR evolved gas analysis CG–MS intermediate characterization 

Notes

Acknowledgements

The authors are grateful to agencies FAPESP (Processes: 2014/22142-4 and 2015/09299-4) and CNPq for support.

Supplementary material

10973_2018_7226_MOESM1_ESM.docx (4.1 mb)
Supplementary material 1 (DOCX 4196 kb)

References

  1. 1.
    Jagtap A, Bhaskar M. Evaluation of antidepressant and antinociceptive activity of escitalopram. Ind J Pharm Edu Res. 2013;47:97–102.Google Scholar
  2. 2.
    Burke WJ, Christopher J, Kratochvil MD. Stereoisomers in psychiatry: the case of escitalopram. Prim Care Companion J Clin Psychiatry. 2002;4:20–4.CrossRefGoogle Scholar
  3. 3.
    Balawejder M, Mossety-Leszczak B, Poplewska I, Lorenz H, Seidel-Morgenstern A, Pistkowski W, Antos D. Resolution of a diastereomeric salt of citalopram by multistage crystallization. Cryst Growth Des. 2012;12:2557–66.CrossRefGoogle Scholar
  4. 4.
    Giridhar T, Srinivasa RK, Srinivasulo G, Gudipati S, Kotaru SR, Thota G. New crystalline form of citalopram diol intermediate useful for preparation of citalopram and its salt used as antidepressant drug. WO2010004575A2. 01/14/2010.Google Scholar
  5. 5.
    Pires SA, Mussel WN, Yoshida MI. Solid-state characterization and pharmaceutical compatibility between citalopram and excipients using thermal and non-thermal techniques. J Therm Anal Calorim. 2016;127:535–42.CrossRefGoogle Scholar
  6. 6.
    Hotová G, Slovak V. Quantitative TG–MS analysis of evolved gases during the thermal decomposition of carbon containing solids. Thermochim Acta. 2016;632:23–8.CrossRefGoogle Scholar
  7. 7.
    Nicolet-ThermoScientific Co. Nicolet EPA Vapor Phase database. Omnic 8.0 software. ThermoScientific, Madison.Google Scholar
  8. 8.
    Coblentz Society, Inc., “Evaluated infrared spectra” in NIST chemistry webbook, NIST standard reference database Number 69, In: Eds. PJ Linstrom, WG Mallard, National Institute of Standards and Technology, Gaithersburg, 20899, http://webbook.nist.gov (recovered at 11/10/2016). Coblentz No. 10480.
  9. 9.
    Coblentz Society, Inc., “Evaluated infrared spectra” in NIST chemistry webbook, NIST standard reference database Number 69, In: Eds. PJ Linstrom, WG Mallard, National Institute of Standards and Technology, Gaithersburg, 20899, http://webbook.nist.gov (recovered at 11/10/2016). Coblentz No. 8839.

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  1. 1.Instituto de Química de São CarlosUniversidade de São Paulo – USPSão CarlosBrazil

Personalised recommendations