Determination of Operating Conditions in Batch Mode

The development of a co-crystallization in solution is similar to the development of the crystallization of the API itself since the mechanisms of nucleation and growth are similar in both cases. Control of the nature of the solid phase is essential during the operation and we have to keep in mind these two following points  

Start the co-crystallization with the desired co-crystal phase. 

Prevent the occurrence of other solid phases due to inopportune primary nucleation events which may lead to the partial or total loss of the cocrystal population by SMPT. 

The first point can be achieved by means of seeding. The second point can be obtained by defining an operating region in the phase diagram over the temperature range of the batch process. Finally in the case of a final desired co-crystal phase which does not fulfil the purity requirements due to the presence of another crystal phase, a retreatment process may be set up with the addition of the correct amount of one of the co-crystal components in order to provoke a SMPT which eliminates this undesirable solid phase and produces co-crystals. 

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