Cocrystallization pathways

Amorphous phases are attractive to study mechanisms of cocrystal formation because they require very small samples (3-5 mg) and can be prepared and studied in situ (by melt-quenching) in a calorimeter or on a microscope stage. Cocrystallization pathways can then be identified and kinetics measured from the analysis of thermal events, photomicrographs and spectroscopic analysis in real time. An example of the cocrystallization of CBZ NCT from an amorphous film of equimolar composition of reactants is shown in Fig. 24. 

Cocrystals can also be prepared in situ in covered depression slides on the polarized optical light microscope or Raman microscope by adding a small drop of solvent to the solid reactants. This has been shown for cocrystals of CBZ NCT with ethanol, ethyl acetate or 2-propanol. Photographs obtained through the polarized light microscope are shown in Fig. 22. These images show cocrystal formation in less than three minutes after solvent addition. In this case, the cocrystallization reaction proceeds by a similar pathway to those of macro-phase suspensions described above. In micro-phases the solvent added must allow for dissolution of both reactants so that concentrations in... 

The lesson to be taken from this study is that the development of a cocrystallization process first requires knowledge of a large part of the phase diagram with temperature and second that the possible kinetic pathways which may occur should be evaluated. Considerations based on thermodynamic... 

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