Crystallographic and physicochemical characterization of salcaprozoic acid: a structural basis for SNAC-enabled drug delivery systems

Salcaprozate sodium (SNAC) is a clinically approved oral permeation enhancer, notably used in the formulation of oral semaglutide. Despite its pharmaceutical importance, the crystallographic information of SNAC or its free acid form, salcaprozoic acid {systematic name: 8-[(2-hydroxyphenyl)formamido]octanoic acid, C₁₅H₂₁NO₄, denoted HNAC}, has not been reported previously. Here, we present the first crystallographic and physicochemical characterization of HNAC using single-crystal X-ray diffraction and complementary analytical techniques. The structure reveals the molecular conformation, hydrogen-bonding network and packing features of HNAC, supported by a complementary solid-state dataset. These findings provide fundamental insights into the structural and physicochemical properties of this physiologically relevant form of SNAC.