In pharmaceutical industry, most active pharmaceutical ingredients (API) are purified via crystallization process. A good crystallization process should be able to reliably reject impurities to suitably low levels and provide the greatest possible yield. From operational point of view, large crystal sizes would enable to faster liquid-solid separation, which include filtration and centrifugation. Crystallized slurry with large crystals and small amount of fines will result in a faster filtration process.

In this talk, the authors will discuss a thermal cycling crystallization process developed for an actual API manufacturing process in Abbott. The thermal cycling process is based upon the Oswald ripening principle and the solid dissolution kinetics: it promotes the crystal growth during cooling while enhancing the small crystal dissolution rate during heating. Results from in-situ FBRM and PVM during the thermal cycling will be discussed and compared with the resulting wetcake resistance and permeability.