Elucidation of lactose fine size and drug shape on rheological properties and aerodynamic behavior of dry powders for inhalation

Abstract

Pulmonary drug delivery has gained great attention in local or systemic diseases therapy, however it is still difficult to scale-up DPI production due to the complexity of interactions taking place in DPI systems and limited understanding between flowability and inter-particle interactions in DPI formulations. Therefore, finding some quantitative parameters related to DPI delivery performance for predicting the in vitro drug deposition behavior is essential. Therefore, this study introduces a potential model for predicting aerodynamic performance of carrier-based DPIs, as well to find more relevant fine powder size and optimal shape to improve aerodynamic performance. Using salbutamol sulfate as a model drug, Lactohale®206 as coarse carrier, Lactohale®300, Lactohale®230, and Lactohale®210 as third fine components individually, the mixtures were prepared at 1% (w/w) drug content accompanied with carriers and the third component (ranging from 3% to 7%), influence of lactose fines size on DPI formulation’s rheological and aerodynamic properties was investigated. The optimum drug particle shape was also confirmed by computer fluid dynamics model. This study proved that pulmonary deposition efficiency could be improved by decreasing lactose fines size. Only fines in the size range of 0–11 μm have a good linear relationship with FPF, attributed to the fluidization energy enhancement and aggregates mechanism. Once exceeding 11 μm, fine lactose would act as a second carrier, with increased drug adhesion. Computational fluid dynamics (CFD) models indicated fibrous drug particles were beneficial to transfer to the deep lung. Furthermore, good correlations between rheological parameters and FPF of ternary mixtures with different lactose fines were established, and it was disclosed that the FPF was more dependent on interaction parameters than that of flowability.