A variety of surface specific techniques have been used to determine the face-specific structure, chemistry, and wettability of model pharmaceutical crystals, i.e., N,n-octyl-d-gluconamide and sulfathiazole (polymorphic forms I and III). The surface energetics of individual crystal faces were investigated by studying their wetting characteristics and interaction with chemically modified silica spheres using colloid probe atomic force microscopy (AFM). Contact angles (dynamic and static), interaction forces, and adhesion properties have been shown to correlate strongly with the face specific surface chemistry. This, in turn, is controlled by the molecular arrangement at the specific crystal face, which has been characterized by time-of-flight secondary-ion mass spectrometry (ToF SIMS) and inferred from molecular models. Of specific note, the magnitude of the adhesion force between a crystal face and a hydrophobic colloid probe is related linearly to the face-specific equilibrium contact angle. These studies further our understanding of the face-specific properties of pharmaceutical crystals and have implications when considering processing, formulation and delivery.
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