A Review of Inverse Gas Chromatography and its Development as a Tool to Characterize Anisotropic Surface Properties of Pharmaceutical Solids

Surface properties can profoundly impact the bulk and interfacial behavior of pharmaceutical solids, and also their manufacturability, processability in drug product processes, dissolution kinetics and mechanism in drug delivery. Variation in the inter- and intra-molecular interactions gives rise to anisotropic surface properties of crystalline solids which display direction-dependent characteristics relative to the orientation of the crystal unit structure. Despite its establishment since the 1950s, inverse gas chromatography (IGC) is still an evolving technology in the field of pharmaceutical R&D. In this review, the principles behind IGC as a physicochemical technique to measure the surface properties of solids are presented. The introduction is followed by an overview of its utility in pharmaceutical R&D, spanning a variety of applications including batch-to-batch variability, solid-solid transitions, physical stability, interfacial behavior in powder processing, and more. For anisotropic materials, IGC has been utilized to characterize the heterogeneity of materials using adsorption and energy distribution functions. Recent development and applications of IGC at finite concentration (IGC-FC) to determine the surface heterogeneity distribution of solids are presented. This methodology overcomes a number of limitations associated with traditional experiments.