Understanding fragility and cohesiveness in spray freeze-dried powders

Characterizing the properties of low-density powders presents significant challenges due to their unique behaviour, such as fragility and cohesiveness during processing and handling. Spray freeze drying (SFD), an emerging technique in pharmaceutical applications, is one method used to produce these powders, but it requires reliable characterization methods. In this study, we developed a novel and straightforward method for quantifying the fragility and cohesiveness of spray freeze-dried powders, combining size distribution analysis with dynamic image analysis and a pressure module. This method not only allows for the identification of fragility inducers, such as mannitol, and cohesion-reducing agents like sodium lauryl sulphate (SLS), but also provides a more comprehensive understanding of material properties. We demonstrate that traditional methods, such as the Hausner Ratio and angle of repose, fail to fully capture these key properties, limiting their utility in powder formulation optimization. Our approach offers an effective way to assess powder behaviour, with important implications for improving the handling and performance of spray freeze-dried pharmaceutical products. • Novel method for quantifying fragility and cohesion in low-density powders. • Developing new spray freeze-drying formulations to enhance powder flow and stability. • Optimizing characterization techniques to improve powder performance. • Introducing an approach for predicting powder behaviour in drug delivery.