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

Abstract

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.

Differentiating Defect and Basal Plane Contributions to the Surface Energy of Graphite Using Inverse Gas Chromatography

“…This manifests itself in some surface energy profiles (see SI figure S6) where the surface energy plateaus before beginning to increase with coverage. This is generally accompanied by peak fronting in the chromatograms which has been associated with probe-probe interactions by Ho et al 29 Where such increases were observed, we removed the relevant data points and only analysed data where the measured surface energy falls or stays constant with increasing probe coverage. While this should minimise the effect of probe-probe 6 interactions, we cannot avoid the fact that surface energy values in the high coverage regime may be slightly over estimated.…”

Understanding the Dispersion and Assembly of Bacterial Cellulose in Organic Solvents

“…To measure the total surface energy of any material we can crudely sum the dispersive term, γ D , and the specific terms, γ sp . 43 γ sp can be determined using IGC, as ΔG sp using: ) i.e. the difference of RTlnV n for the specific probe and the corresponding dispersive reference line (as shown in figure 3a).…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…PXRD is a well-established technique for quantification of percentage crystallinity existing initially or transformed during manufacturing [151]. X-ray photoelectron scattering (XPS) [152] and inverse gas chromatography (IGC) [153] are very sensitive techniques for surface analysis and anisotropy. DVS plays an important role in calculating the hygroscopicity and the level of intermolecular interactions [154], while TGA may be used to calculate the moisture level in the solid form.…”