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.
- liquid propofol
- solid crystalline powder
- solid drug forms
- crystal structure
McKellar, S. C., Kennedy, A. R., McCloy, N. C., McBride, E., & Florence, A. J. (2014). Formulation of liquid propofol as a cocrystalline solid. Crystal Growth and Design, 14(5), 2422-2430. https://doi.org/10.1021/cg500155p