(524b) Design of API Amorphous Precipitation Processes Via the Use of an FBRM Based Method

This presentation will provide an FBRM based method to aid in the design of amorphous precipitation processes for active pharmaceutical ingredients. The attributes of amorphous particles formed during precipitation from solution are dependent on the glass transition temperature of the system. Glass transition temperature measurements of amorphous wetcakes and slurries are difficult to obtain using differential scanning calorimetry. This FBRM based method provides a ‘softening temperature’ of amorphous particles in suspension. The softening temperature is shown to correlate with the glass transition temperature of amorphous solids (as determined by differential scanning calorimetry). By determining the softening point of a precipitation system as a function of solvent composition, a process can be designed to deliver desired particle properties. A case study will be provided where a precipitation process was developed to provide a narrow range of powder specific surface areas to meet formulation requirements. Another case study will be provided where the filtration rate of an amorphous slurry was drastically improved by adjusting the temperature of a precipitation. The optimal temperature to maximize filtration rate was determined by softening point measurements obtained via the FBRM based method.