Formulation of Liquid Propofol as a Cocrystalline Solid

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.