Solvatomorphic impurities

In this chapter, the question of small amounts of polymorphic and solvatomorphic impurities in a bulk solid will be addressed. The most useful methods for performing such work will be outlined, and illustrated with appropriate examples. 

It should be noted that none of the terminologies given above adequately highlights polymorphic, solvatomorphic, and chiral impurities (see Section III). 

In addition to the residual solvents, polymorphic, solvatomorphic, and chiral impurities mentioned previously, impurities in a pharmaceutical compound or a new chemical entity (NCE) can originate during the synthetic process from raw materials, intermediates, and/or by-products. Raw materials are usually produced to lesser purity requirements than a drug substance. Therefore, it is easy to understand why they could include a number of components that in turn could have an impact on the purity of the drug substance. 

There is no doubt that single crystal X-ray diffraction is a powerful technique for the study of polymorphs and solvatomorphs, but it is equally apparent that this methodology is not well suited for the routine evaluation of the crystalline state of powdered solids. It is definitely not a technique that one would want to use in the determination of polymorphic phase impurities in a sample, since by definition only a single crystal is studied at one time. That crystal would certainly be phase-pure, and its quantitative analysis not... 

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