(381b) Strategies for Crystallization Development of Process Intermediates in Early and Late Stage Manufacturing Processes

Several tools are available for modeling crystallization attributes such as in silico solubility prediction using discreet sets of solubility screening data and regression modeling of temperature dependent solubility to aid in design of crystallization. These techniques are sometimes underutilized during intermediate isolations but provide a framework for making better judgements in initial crystallization design for process intermediates. In one case study, this approach was used to discover a suitable replacement crystallization for isolation of crude API from a high salt load process stream and was further developed to engineer Particle size control in the API isolation. In a second case study, use of distillation models in Dynochem led to the discovery of a suitable solvate form of a process intermediate that enabled complete purge of impurities originating from vendor lots of raw material in the chemical process, providing a "purity gate" which simplified the Quality attribute landscape in a fast moving development project. Prior to this discovery the material was an amorphous oil. A similar approach was used in later intermediate steps to control impurities and improve crystallization predictability and performance.