(187h) Utilization of Population Balance Models to Develop a Continuous Crystallization Process; Process Design Using Optimization

Due to material and time constraints, experimentation alone often cannot provide a means for design optimization of continuous crystallization processes within the pharmaceuticals industry.  While several conventional process design software packages offer the ability to handle process optimization, such software packages often lack a robust means for predicting the effect of changing process variables on the corresponding particle size distributions (PSD).  In the crystallization of active pharmaceutical ingredients, specific PSD requirements are often a crucial to the manufacturability and bioavailability of the final drug (solid dosage form).  In this talk, we use a combined population balance and process design software (e.g., gCRYSTAL, Process Systems Enterprises) as a means for process optimization for continuous crystallization.  In performing this process optimization, we use rate constants for nucleation and growth that were obtained from regressed experimental data using the same software package (the details of this regression are contained in the talk “Utilization of Population Balance Models to Develop a Continuous Crystallization Process; Determination of Crystallization Kinetics,” which is also being given at this conference).  Furthermore, we are able to perform this process optimization with the assertion of constraints on the PSD for the optimal solution.  This talk concludes with our insights regarding the implementation of process optimization as a part of a proposed “universal” work flow for the design of continuous crystallizations.