Terahertz spectroscopy to identify the polymorphs in freeze-dried Mannitol.

We show how terahertz time-domain spectroscopy (THz-TDS) in the range from 0.1 to 7.5 THz can be used to identify the polymorphs of Mannitol, a frequently used excipient in the freeze drying industry. The results are subsequently used to study the effect that different freeze drying techniques have on the formation of these polymorphs. We find that, depending on the freeze-drying technique, the Mannitol either crystallizes in the delta form, or in a mixture of both the delta form and the beta form. The results are in agreement with conventional X-ray diffraction measurements used to identify the polymorphs.

Quasi-near field terahertz generation and detection.

We describe a simple terahertz (THz) time domain spectrometer with a bandwidth extending up to 7.5 THz. We show that by keeping the generation and detection crystals close to each other a high signal-to-noise ratio (SNR) can be achieved without using lock-in detection and dry nitrogen flushing. The observed spectra show very good agreement with the spectra calculated based on a simple model which includes phase matching and absorption in the generation and detection crystals. Using this set-up we have measured the absorption lines in D-tartaric acid from 0.5 THz up to 7 THz. We show that the high frequency region > 3 THz is the better choice to measure small changes in the water content of a hygroscopic sample compared to the low frequency region.