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. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:932-940, 2010