Inverse gas chromatography: considerations about appropriate use for amorphous and crystalline powders

The use of inverse gas chromatography to assess surface properties of a range of pharmaceutical powders was examined. The powders were two sources of hydroxy propylmethyl cellulose (HPMC), microcrystalline cellulose, magnesium stearate, and acyclovir. These were selected to cover a range for properties from amorphous to crystalline, hydrophilic to hydrophobic, and high to low aqueous solubility. It was found that many powders gave a similar value for the dispersive surface energy, which is surprising given the differences in chemical nature. It is likely that this is due to the use of infinite dilution giving rise to the study of specific regions of the powder surface only. The values obtained for dispersive energies were not influenced by packing mass or flow rate of the carrier gas. The retention of polar probes on the column was a concern for the amorphous HPMC samples. This gave rise to derived values for acid-base nature which varied depending on sample mass and carrier gas flow rate. The data show that care must be taken when studying amorphous samples for which it is possible to obtain diffusion into the material rather than just surface adsorption of probes. Despite these problems, it was still possible to differentiate between the samples (including differences between the two HPMC samples) by use of polar probes. It was also possible to see differences in absorption into the sample, reflecting the different physical forms. For example, microcrystalline cellulose behaved very differently to HPMC. It can be concluded that inverse gas chromatography is a valuable characterization tool, but it must be used with care especially with respect to polar probes on amorphous samples.