Nucleation control in solution mediated polymorphic phase transformations: The case of 2,6-dihydroxybenzoic acid

This contribution describes the kinetics of the solution mediated phase transformation between forms 1 and 2 of dihydroxybenzoic acid. It is shown how a combination of kinetic, morphological, and modeling data can be used to give a full description of the rate-determining process in such a transformation. Surprisingly, secondary nucleation is found to dominate the kinetic processes. Such a phenomenon is well-known in continuous crystallization but is reported here for the first time in a polymorphic phase transformation. This observation has significant consequences for process and product control in the pharmaceutical and specialty chemicals industries.