On the relationship between drug and carrier deposition from dry powder inhalers in vitro

Abstract

Dry powder inhaler formulations usually contain micronised drug particles and lactose as a carrier. Although the fine particle fraction (FPF) of drug from many different formulations has been reported previously, there have been few studies which have determined the deposition of both drug and carrier. In this study, drug and lactose particle deposition was characterised by means of a twin stage impinger (TSI) and an Andersen cascade impactor (ACI). The flow rate was varied between 28.3–90 l/min. The particle size distribution of the lactose carrier in the formulation highly influenced the drug FPF. The higher the flow rate, the higher the FPF of drug when micronised lactose was employed in the formulation. However, when a larger particle size carrier (Lactochem lactose) was employed in the formulation, the FPF was not changed when the flow rate increased (30–90 l/min). Deposition patterns of fine lactose carrier from each formulation at different air flows were broadly similar to those of the drug. At 28.3 l/min, the drug particles were deaggregated to a median particle size of 4.89±0.11 μm (Lactochem formulation) and 4.07±0.09 μm (micronised lactose formulation). When the flow rate was increased to 60 l/min, the degree of dispersion that resulted led to the deaggregation of the drug to particles with a median size of 2.80 μm in both formulations. The coarser particles of lactose in fractions of carrier containing a wide particle size distribution impacted in the throat and preseparator of the ACI and only particles less than 10 μm entered stage 0 to stage 7. The median size of the lactose obtained in both formulations at a flow rate of 28.3 and 60 l/min varied between 5.67 μm to 4.42 μm and hence the carrier particles did not penetrate to stage 3 in the ACI. These results show that in impactors the deposition pattern of both drug and carrier is highly dependent upon air flow rate and particle size distribution of the carrier used to prepare the formulation.