(661c) Development of a Laboratory and Mathematical Model to Predict Scale up Performance of an API Slurry Milling and Isolation Step

Control of Active Pharmaceutical Ingredient particle size can be a significant challenge when designing a crystal that yields good flow properties for drug product formulation.  This must also be balanced with a need for ensuring adequate bioavailability and content uniformity of the formulated product. When slurry milling can be employed for particle size control, a dry milling step and the associated costs and potential exposure can be significantly reduced.   In this study, we examine an Active Pharmaceutical Ingredient crystallization requiring careful particle size control and the subsequent scale up for manufacturing.   This analysis includes development of a laboratory model and a mathematical model to predict milling performance, including a prediction of system shear rate at full manufacturing scale to determine milling and attrition of particles for optimization of particle size and isolation cycle time.