(479e) Application of Methods to Quantify Maximum Potential Segregation and Actual Segregation Risk to Design of Pharmaceutical Blends

As described in a recent publication (Gentzler Tardos, Michaels, 2015), a methodology for assessing the tendency of pharmaceutical powders to demix due to segregation is useful for predicting content uniformity risks for solid dosage forms. Examples of how pharmaceutical formulations in development can be characterized to evaluate the potential for segregation, and optimized to reduce the actual risk of content uniformity issues upon scale-up are provided. Modification to active components and excipient properties are considered with respect to typical direct compression and granulation processes. A systematic risk assessment approach for multi-component blends emerges, and examples of how the methodology can be used in material-conserving predictive measurements during development are given for both high and low dose products. Use of lab-scale measurements to understand sensitivity to raw material properties in lieu of pilot and commercial-scale production tests is described.