Relative Stability of the Solid Phases in Solution

During the crystallization in solution, several solid phases may develop separately or simultaneously. The development in solution of CBZ single crystals 

Domain 1 a solution represented by a point in this domain is undersaturated with respect to CBZ crystals, NCT crystals and CBZ/NCT cocrystals. No crystalline phase is able to develop. 

Domain 2b a solution in this domain is supersaturated with respect to CBZ crystals and CBZ/NCT co-crystals. CBZ and CBZ/NCT solid phases are able to develop together. With regard to their respective solubilities, the CBZ/NCT eo-crystal is the metastable phase whereas the CBZ crystal is the stable one. 

Domain 4a a solution in this domain is supersaturated with respect to CBZ crystals and CBZ/NCT co-crystals. These two crystalline phases are able to nucleate and grow together temporarily. With regard to the solubilities, CBZ is the metastable phase, whereas CBZ/NCT is the stable one. Domain 4b a solution in this domain is supersaturated with respect to CBZ crystals, NCT crystals and CBZ/NCT co-crystals. These three crystalline phases are able to nucleate and grow together temporarily. With regard to the solubilities, CBZ and NCT crystals are the metastable phases, whereas CBZ/NCT is the stable one. 

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Co-crystals represent a novel class of crystalline solids which possess scientific and regulatory advantages along with enormous intellectual property potential. In the earlier stages of pharmaceutical process development, an efficient cocrystal screening is essential in order to determine the different possible stoichiometries and the different polymorphic forms for each stoichiometry. When all the different phases are identified, the relative stability of the solid phases in solution has to be determined. This step requires the construction of the... 

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