Process Optimization of Filling Up Crystallization

The optimization of filling up crystallization of a specific active pharmaceutical ingredient (APIe) is presented and discussed. Filling up crystallization is a special cooling crystallization method the main goal of which is to narrow the crystal size distribution (CSD) of the product. Fast cooling of the solution is achieved in the first section of the cooling profile as the hot solution of the API for crystallization is fed into the crystallizer, where a constant but significantly lower temperature is maintained by choosing a suitable addition rate of the hot solution and utilizing the cooling efficiency of the crystallizer. The process of determination for formulation of the crystals occurs during the filling up period of the crystallization. As a result of optimization, a parameter range is specified from which the process parameters can be chosen ensuring that the product specifications comply with the limitations.