Co-crystals and their Characterization

To date, a universal and agreeable definition of what constitutes a co-crystal is still not available. Other chapters of this monograph will deal with this issue in more detail. However, in this chapter, co-crystalline materials will possess the following descriptors  

In particular, infrared spectroscopy can be a very powerful tool in detecting co-crystal formation, especially when a carboxylic acid is used as a co-former and/or when a neutral hydrogen bond is formed between the 

1700 cm and aweaker C O stretch around 1200 cm while a carboxylate anion (-COO ), due to resonance, displays a single C-O stretch in the fingerprint region of 1000-1400 cm Additionally, if a neutral intermolecular O H N hydrogen bond has formed between the components, then two broad stretches around 2450 cm and 1950 cm will be observed.  

A number of different characterization techniques mentioned above are used to help distinguish between co-crystals and salts and it should be noted that in some cases differentiation between the two may still be difficult. It should also be pointed out that although salts and co-crystals often posses different properties (e.g., stability or solubility), these issues from a pharmaceutical development standpoint may not be influential as long as the process can be monitored and closely controlled. However, for intellectual property (IP) rights and regulatory issues, differentiating between a co-crystal and a salt is important. 

4 Co-crystals and their Role in the Pharmaceutical Development Process 

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