Formulation of liquid propofol as a cocrystalline solid

Scott C. McKellar, Alan R. Kennedy, Neil C. McCloy, Eileen McBride, Alastair J. Florence

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


This work details a crystal engineering strategy to obtain a novel solid form of the liquid drug molecule propofol using isonicotinamide as a cocrystal former. Knowledge of intermolecular hydrogen bonded supramolecular synthons has been exploited to select a potential cocrystal former based on the likely growth unit formed. The structure of the cocrystal, solved using single-crystal X-ray diffraction, is reported, confirming the molecular packing and key intermolecular interactions adopted in the novel solid form. The potential to enhance a drug’s properties is demonstrated by an increased melting point compared to the native drug form, such that the liquid drug becomes a stable solid at room temperature. Unusually, the propofol/isonicotinamide complex has three structurally similar, temperature-dependent polymorphs, and the crystal structure of each form is reported herein.
Original languageEnglish
Pages (from-to)2422-2430
Number of pages9
JournalCrystal Growth and Design
Issue number5
Early online date27 Feb 2014
Publication statusPublished - 27 Feb 2014


  • liquid propofol
  • solid crystalline powder
  • solid drug forms
  • crystal structure


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