Polymorphism single-crystal characterisation

Among the earliest ionic liquids for which single-crystal characterisation of polymorphs has been reported are 1,3-dialkylimidazolium chlorides and bromides [230, 566]. Monoclinic and orthorhombic forms of [C4inim]Cl are associated with differences in butyl conformation, with a conputational study [567] suggesting that the free energy difference associated with a single... 

A detailed account of polymorphism and its relevance in the pharmaceutical industry is given elsewhere in this volume and in the literature [42,46,47]. This section will focus on the use of vibrational spectroscopy as a technique for solid-state analysis. However, it should be noted that these techniques must be used as an integral part of a multidisciplinary approach to solid-state characterisation since various physical analytical techniques offer complimentary information when compared to each other. The most suitable technique will depend on the compound, and the objectives and requirements of the analysis. Techniques commonly used in solid-state analysis include crystallographic methods (single crystal and powder diffraction), thermal methods (e.g. differential scanning calorimetry, thermogravimetry, solution calorimetry) and stmctural methods (IR, Raman and solid-state NMR spectroscopies). Comprehensive reviews on solid-state analysis using a wide variety of techniques are available in the literature [39,42,47-49]. 

There are a number of methods that can be used to characterise polymorphs of a drug substance. Demonstration of a non-equivalent structure by single-crystal X-ray diffraction [ 11 ] is currently regarded as the definitive evidence of polymorphism. X-ray powder diffraction (XRPD) can also be used to support the existence of polymorphs. However supporting... 

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