Mechanistic and kinetic insight into spontaneous cocrystallisation of isoniazid and benzoic acid

Inese Sarcevica, Liana Orola, Karol Nartowski, Yaroslav Khimyak, Andrew Round, Laszlo Fabian

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34 Citations (Scopus)
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Solid-state cocrystallisation is of contemporary interest, because it offers an easy and efficient way to produce cocrystals, which are recognized as prospective pharmaceutical materials. Research explaining solid-state cocrystallisation mechanisms is important, but still too scarce to give a broad understanding of factors governing and limiting these reactions. Here we report an investigation of the mechanism and kinetics of isoniazid cocrystallisation with benzoic acid. This reaction is spontaneous; however its rate is greatly influenced by environmental conditions (humidity and temperature) and pre-treatment (milling) of the sample. The acceleration of cocrystallisation in the presence of moisture is demonstrated by kinetic studies at elevated humidity. The rate dependence on humidity stems from moisture facilitated rearrangements on the surface of isoniazid crystallites, which lead to cocrystallisation in the presence of benzoic acid vapour. Furthermore, pre-milling the mixture of the cocrystal ingredients eliminated the induction time of the reaction and considerably increased its rate.
Original languageEnglish
Pages (from-to)2981–2992
Number of pages12
JournalMolecular Pharmaceutics
Issue number8
Early online date18 Jun 2015
Publication statusPublished - 3 Aug 2015


  • Cocrystallization
  • mechanochemistry
  • effect of spinning
  • spontaneous reactions
  • solid-state kinetics

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