Efficient Resolution of Racemic Guaifenesin via Batch-Preferential Crystallization Processes

The potential of enantioseparation processes based on preferential crystallization (PC) in single and coupled batch configuration is demonstrated for the active pharmaceutical ingredient (API) guaifenesin. After presenting thermodynamics and kinetics for the system guaifenesin in isopropanol, two batch crystallization-based separation approaches are exploited. First, single-batch-preferential crystallization in two different solvents has been studied. The results are described in terms of productivity, purity, and yield, with an emphasis on the role of the solvent in the enantioseparation outcome. Second, we demonstrate the applicability and performance of an alternative approach, namely, coupled batch-preferential crystallization and selective dissolution (CPCD) for the system guaifenesin/isopropanol, and highlight the advantages and drawbacks of this promising concept.