LAUSR

Low-solubility active pharmaceutical ingredients (APIs) are increasingly formulated as nanosuspensions comprising pure API nanocrystals (i.e. d50 ~ 100 nm) stabilized by surfactants or polymeric steric stabilizers [1]. The physicochemical properties of such nanosuspensions are characterized extensively using a range of predominantly bulk analytical techniques including imaging, spectroscopy and thermal analysis [1]. These techniques elucidate the overall properties of the nanosuspension but do not directly assess the local atomic structure of individual API nanocrystals. Revealing the local structure of individual nanocrystals could enhance product development, motivating technique development. Transmission electron microscopy (TEM) is a natural choice for nanoscale characterization but its application to APIs has been limited by electron beam damage. Here, we report on the development and application of new electron diffraction microscopy techniques, namely scanning electron diffraction (SED) microscopy [2] and continuous rotation tomography [3, 4], that minimize electron dose to overcome previous limitations. These techniques enable detailed characterization of individual cabotegravir (GSK1265744) nanocrystals, similar to those used in the formulation of cabotegravir long-acting nanosuspensions.