FBRM and PVM investigations of the double feed semi-batch crystallization of 6-aminopenicillanic acid

Abstract

6-Aminopenicillanic acid (6-APA) is a crucial pharmaceutical intermediate in the chemistry of semi-synthetic antibiotics. The focused beam reflectance measurement (FBRM) technology and particle vision measurement (PVM) technology were employed to the processes of online-monitoring of 6-APA crystallization behavior in a double-feeding semi-batch crystallizer. Experiments were carried out with four kinds of double-feeding policies and the results were compared with the traditional single-feeding. Records and analysis of FBRM indicated that the nucleation of double feeding policy was much higher than single policy, and chord length of 6-APA was almost determined and had little change after the nucleation peak. Ostwald ripening process had no significant effect on further growth of 6-APA crystal. PVM images showed that the crystal habit of 6-APA was continuously changed during the crystallization process. The development of (002) face in the final crystal for the five feeding policies were different.

Keywords

6-aminopenicillanic acid / crystallization / double-feeding / FBRM / PVM / crystal habit

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Acknowledgements

We thank North China Pharmaceutical Group Corp. (NCPC) for supplying 6-APA and the State Research Center of Industrialization for Crystallization Technology (China) for financial support.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg