Variable temperature XRPD

Since it was known that theophylline monohydrate can be thermally dehydrated to form either the stable Form I or the metastable Form I, the effect of different drying methods on the phase composition was studied [89], Using either a multichamber microscale fluid bed dryer or the hot stage of a variable-temperature XRPD diffractometer, Form I was produced when the drying was conducted at 40-50°C. Drying at 60°C in the VT-XRPD unit yielded only Form I, while mixtures of products were produced in the microscale fluid bed dryer even at temperatures as high as 90 °C. 

Figure 3.3.6 Variable temperature XRPD measurements applied to the investigation of the dehydration of barbituric acid dihydrate with formation of Form I of barbituric acid [12].

Figure 3.3.15 Variable temperature XRPD measurements showing the monohydrate thermal behavior. The diffraction pattern of the monohydrate is shown at 32 and 50 C between 50 and 60 C dehydration leads to initial formation of the (3 and 6 forms between 80 and 95 C the monohydrate goes through complete dehydration leaving only the (3 and...

More specialized techniques are often useful in form characterization. For example, TG-infrared spectroscopy or TG-mass spectroscopy combinations allow identification of volatile materials, making hydrate or solvate identification easier. Variable-temperature and variable-humidity sample chambers on XRPD or vibrational spectroscopy instruments provide the ability to watch crystal form changes associated with changing conditions. The decision to use such methods depends on the characteristics of the particular drug substance under study. 

Modulated temperature x-ray powder diffraction (XRPD) is being used increasingly in the pharmaceutical industry both at preformulation and at formulation stages. Airaksinen et al. (11) studied polymorphic transitions during drying using two methods a multichamber microscale fluid-bed dryer or a variable temperature powder x-ray diffractometer. Relative amounts of different polymorphic... 

A very useful supplement to XRPD is to use a variable temperature hot stage as the sample holder, enabling one to heat a sample to any desired temperature and thus study the crystallographic consequences of thermally induced phenomena. Such a VT-XRPD system equipped with a heatable sample holder has been described which permitted accurately controlled heating up to 250 The system was used to study the phase transformation of phenanthrene and the dehydration of caffeine hydrate. 

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