(187g) Utilization of Population Balance Models to Develop a Continuous Crystallization Process; Determination of Crystallization Kinetics | AIChE

(187g) Utilization of Population Balance Models to Develop a Continuous Crystallization Process; Determination of Crystallization Kinetics

Authors 

Lovette, M. A., Eli Lilly


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).  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.  Furthermore, we are able to perform this process optimization with the assertion of constraints on the PSD for the optimal solution. 

In this talk, experiments are conducted to provide the necessary data needed to regress kinetic parameters associated with crystallization; nucleation, growth and agglomeration.  This talk will discuss both the experimental and computation aspects of the work and subsequent refinements as continuous crystallization results are collected later in development.  This is the first of two discussions at this meeting, illustrating our proposed “universal” work flow for the design of continuous crystallizations.