Characterization of anhydrous and hydrated pharmaceutical materials with THz time-domain spectroscopy

The identification of anhydrous and hydrated forms of pharmaceutical substances is of great importance in pharmaceutical science and industry. We report the use of THz time-domain spectroscopy (THz-TDS) for pseudopolymorph investigation. The anhydrous forms of pharmaceutical substances including caffeine, theophylline, D-glucose, and ampicillin exhibit different THz absorption spectra from their hydrated forms, presumably due to their different intermolecular vibrational modes mediated by hydrogen-bonding. The data from X-ray powder diffractometry (XRPD) confirm the crystallinity differences between the anhydrous and hydrated forms. The temperature-dependent THz spectra of caffeine hydrate were also recorded, and it demonstrates that THz-TDS can be used to monitor the dehydration process of drug hydrates. We conclude that THz-TDS is an advantageous technique for the pseudopolymorph identification and study, and has great potential to become a process analytical technology (PAT) in pharmaceutical production and quality control.