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.
Liu
Hai-Bo
HB
Center for Terahertz Research, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Chen
Yunqing
Y
Zhang
X-C
XC
D000667:Ampicillin / Q000737:chemistry; D002110:Caffeine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005947:Glucose / Q000737:chemistry; D006860:Hydrogen Bonding; D013057:Spectrum Analysis / Q000379:methods*; D013806:Theophylline / Q000737:chemistry; D014867:Water; D014961:X-Ray Diffraction
D014867:Water; D002110:Caffeine; D000667:Ampicillin; D013806:Theophylline; D005947:Glucose