This research article provides an in-depth analysis of the effects of lagering conditions on the performance of Dry Powder Inhalers (DPIs). The study systematically evaluates a range of physicochemical properties under different storage conditions and time periods. The research further investigates the interfacial behavior of Fluticasone Propionate (FP) samples with various substances and compares the in vitro performance of binary and tertiary DPI formulations. The findings of this study can significantly contribute to the understanding and prediction of inter particulate forces of secondary processing of APIs in DPI systems, which is crucial for optimizing DPI product performance.