265335 Crystallization of Active Pharmaceutical Ingredients in Scrapped Surface Crystallizers

Tuesday, October 30, 2012: 9:45 AM
Oakmont (Omni )
Jie Chen1, Shin Yee Wong1 and Allan S. Myerson2, (1)Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, (2)Novartis-MIT Center for Continuous Manufacturing & Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA

Scraped-surface heat exchanger (SSHE) (Härröd, M. 1986) is used widely in the chemical and food industries, for example the separation of para-xylene from xylene mixtures, the separation of chlorinated benzenes, the production of ice cream and margarine and etc. The scrapping motion minimizes fouling and improves the heat-transfer rates by removing the solid layer on the wall and transferring solid to the bulk. Despite SSHE’s proven efficiency, its application in pharmaceutical crystallization is very limited.

To explore the concept of SSHE, a laboratory scale scraped surface crystallizer (SSC) was designed and tested using several active pharmaceutical ingredients (API) of different crystal characteristics (needles, rods, fines, and aggregates). The crystallizer was designed using a MultiMaxTM 50 mL reactor with a custom made PTFE anchor impeller. The close clearance (~ 1 mm) between the impeller and the reactor’s interior wall prevented crystal encrustation on both the side and bottom wall. The temperatures of all crystallization experiments were controlled using the MultiMaxTM station.

The performance of SSC was investigated for cooling and anti-solvent crystallizations.  Crystallization kinetics, mixing efficiency, slurry loading tolerance of SSC were evaluated and compared to a conventional stirred tank crystallizer. The results show that SSC can operate at a significantly lower stirring speed for suspension of thick slurry. In addition the crystals produced from SSC are significantly larger, and higher yield was observed due to minimal encrustation on the crystallizer wall. This study showed that SSC is suitable for pharmaceutical crystallization applications, especially those processes with high solid loading of fines and needle-like crystals.

Härröd, M., “Scraped Surface Heat Exchangers”, J. Food Proc. Eng., 9, 1, 1986.

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