Available online 25 August 2022
AbstractPulmonary 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 - 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.
Keywordsdry powder inhaler (DPI)
optimum fines size and shape
computational fluid dynamics
lung deposition prediction
AbbreviationsCFDcomputational fluid dynamics
FPFfine particle fraction
COPDchronic obstructive pulmonary disease
BFEbasic flowability energy
PCAprincipal component analysis
RSDrelative standard deviation
PSDparticle size distribution
SEMscanning electron microscopy
NGINext Generation Impactor
MMADmass median aerodynamic diameter
D10volumetric diameter value at 10% of cumulative distribution
D50volumetric diameter value at 50% of cumulative distribution
D90volumetric diameter value at 90 % of cumulative distribution
DFsregional deposition fractions
PC (1;2)principal component (1;2)
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