(577b) Scale-Independent Micronization: QbD Via a Specific Energy Model

It is well established in micronization theory that specific energy provides a holistic approach to evaluating and understanding the particle size reduction operation, and it can be used to fully characterize process performance and robustness. Utilizing a Fluid Energy spiral jet mill operating at ambient temperature, and nitrogen as the feed/grind gas, three operating parameters (Venturi gas pressure, grind gas pressure, and solid material feed rate) can be actively varied in the micronization process, each of which contribute to the calculated total specific energy. This study examined the application of a specific energy model to develop a scale-independent micronization process for commercial production. To develop the model, 34 development runs were performed across a 4” mill and an 8” mill where the Venturi gas pressure, grind gas pressure, and solid material feed rate were varied to investigate the impact of specific energy on the particle size of the micronized drug substance (i.e. output X₉₀). The data gathered at both scales adhere to the same curve, confirming the scale-independent nature of the specific energy model. With specific energy as the underlying mechanism for particle size reduction, the model was used to determine an appropriate registered range for specific energy to achieve the desired particle size distribution. In conclusion, predictive specific energy models can be implemented to create a scale-independent micronization design space; however, these product-specific models will only be applicable when used to predict performance using mills with similar internal geometries, operating principles and conditions, and processing gas.