Examples of Crystal Form Identification and Characterization

A series of crystallization experiments under a variety of conditions led to the discovery of two new crystal forms, a third anhydrate and a previously unreported monohydrate. Thorough study of the appearance and thermal behavior of the monohydrate led to the conclusion that it, in fact, is the y form reported by Groth the third anhydrate form was designated 6. The MNPU molecule adopts four different conformations in the four crystal structures as shown in Fig. 3.3.8 hence, the system exhibits conformational polymorphism [30]. 

The 13C solid state NMR spectra for the a, 3 and monohydrate forms, shown in Fig. 3.3.11, clearly exhibit distinguishing characteristics for each of the three forms. 

While the HSM experiments often provide dramatic visual evidence for phase transformations, the calorimetric methods (e.g. DSC/TGA) can provide precise thermodynamic data and quantitative information on the composition and nature of solvates and hydrates. The DSC traces for the a, 3/8 and monohydrate are shown in Fig. 3.3.13 and 3.3.14. They confirm the thermal events observed in the HSM experiments. 

The connection between the thermal and structural aspects of these events can be followed by carrying out XRPD studies as a function of temperature. Such an experiment is demonstrated in Fig. 3.3.15. 

Since different crystal forms have different structures, they can, potentially, exhibit different physical properties and different responses to experimental analytical methods. Some of the more commonly used of these methods have been demonstrated above. A central question for any polymorphic system is the relative stability of the various crystal forms. As noted above, these may be investigated qualitatively by HSM methods, and more quantitatively using thermal analytical techniques. The combined results of these measurements are conveniently summarized on a semi-empirical energy-temperature diagram [31], as shown in Fig. 3.3.16. The thermal 

---

MgO is a particularly well studied oxide the structure of the (100) single crystal surface is extremely flat, clean, and stoichiometric. Recent grazing incident X-ray scattering experiments have shown that both relaxation, -0.56 0.4%, and rumpling, 1.07 0.5%, are extremely small [66]. However, no real crystal surface consists of only idealized terraces. A great effort has been undertaken in recent years to better characterize the MgO surface, in particular for polycrystalline or thin-film forms which in some cases exhibit an heterogeneous surface, due to the presence of various sites. All these sites can be considered as defects. The identification and classification of the defects is of fundamental importance. In fact, the presence of appreciable concentrations of defects can change completely the chemical behavior of the surface. A typical example is that of the reaction of CO on MgO (see 3.1). 

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. 

---