The role of intrinsic fines in the performance change of expired lactose carriers for DPI applications.

Dry powder inhalation offers a well-established administration route for either local or systemic drug delivery. Lactose-based powder blends still build the basis of respiratory drug delivery, despite of numerous emerging formulation approaches. The amount of fine lactose excipients, either extrinsic or intrinsic, crucially influences the aerodynamic performance of the corresponding blend. This study highlights the role of intrinsic fines as a fundamental performance affecting parameter during storage and expiry of lactose carrier bulk. We showed that intrinsic fines play an inferior role after expiring compared to fresh batches. If strongly adhering or even merged fines regain their mobility and contribute to the dispersion (by removal and re-addition), it will significantly enhance drug delivery. Furthermore, we provide evidence for decreased mobility of intrinsic fines caused by humidity (e.g., during inappropriate storage) resulting in decreased powder fluidisation.