Pharmaceutical Research

, Volume 32, Issue 1, pp 300–310 | Cite as

Predicting Drug Substances Autoxidation

  • P. LienardEmail author
  • J. Gavartin
  • G. Boccardi
  • M. Meunier
Research Paper



Chemical degradation and stability in formulation is a recurrent issue in pharmaceutical development of drugs. The objective of the present study was to develop an in silico risk assessment of active pharmaceutical ingredients (APIs) stability with respect to autoxidation.


The chemical degradation by autoxidation of a diverse series of APIs has been investigated with molecular modelling tools. A set of 45 organic compounds was used to test and validate the various computational settings. Aiming to devise a methodology that could reliably perform a risk assessment for potential sensibility to autoxidation, different types of APIs, known for their autoxidation history were inspected. To define the level of approximation needed, various density functional theory (DFT) functionals and settings were employed and their accuracy and speed were compared.


The Local Density Approximation (LDA) gave the fastest results but with a substantial deviation (systematic over-estimation) to known experimental values. The Perdew-Burke-Ernzerhof (PBE) settings appeared to be a good compromise between speed and accuracy.


The present methodology can now be confidently deployed in pharmaceutical development for systematic risk assessment of drug stability.


Degradation Autoxidation Computational chemistry Pharmaceutical DFT 



We wish to express our deep acknowledgement to several individuals for assistance encouragement and advice: Jean-René Authelin, Antonio Guerreiro, Jérome Kieffer, Nicolas Marchand and Guy Rossey for project initiation and scientific inputs.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • P. Lienard
    • 1
    Email author
  • J. Gavartin
    • 2
  • G. Boccardi
    • 3
    • 4
  • M. Meunier
    • 2
  1. 1.Pharmaceutical Science DepartmentSanofi R&DVitry-sur-Seine CedexFrance
  2. 2.AccelrysCambridgeUK
  3. 3.Analytical SciencesSanofi Research Centre of MilanMilanItaly
  4. 4.Institute for Chemical and Biochemical Research via G. Colombo 81MilanItaly

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