Nucleation, Growth, and Solvated Behavior of Erythromycin as Monitored in Situ by Using FBRM and PVM

The application of in situ FBRM and PVM in monitoring the erythromycin dilution crystallization process and the transformation of erythromycin solvates is introduced. Influences of seeding strategies on nucleation and growth were examined in acetone aqueous solutions. It is noted by FBRM monitoring that the dominant chord length of crystal products is dependent on the supersaturation when seed crystals are added. Higher supersaturation leads to a smaller dominant chord length. In the crystallization process, breakage and agglomeration are not determined, and secondary nucleation mainly originates from induced nucleation by local high supersaturation resulting from water addition. The transformation process from metastable erythromycin acetone solvate to stable dihydrate was successfully monitored in pure water by using both PVM and FBRM, and the transformation mechanism can be identified as mediated-solution phase transformation. PVM is proven to be more appropriate to monitor transformation between erythromycin solvates as compared with FBRM.