The Effect of Carrier Particle size on Adhesion, Content Uniformity and Inhalation Performance of Budesonide using Dry Powder Inhalers

Abstract

Low drug delivery efficiency to the lower airway regions is still a major challenge for dry powder inhaler (DPI) formulations. Several studies were reported on the effect of drug particle size on DPI performance; however, much less attention has been paid to particle size of the carrier. The purpose of this study was to provide, for the first time, a systematic study showing the effect of lactose carrier particle size on aerosolisation efficiency of budesonide from Aerolizer® inhaler device. The results showed that the smaller the lactose particle size the weaker the budesonide-lactose adhesion forces within DPI formulations and consequently higher amounts of budesonide were delivered to lower airway regions. However, it was found that the smaller the lactose particle size the poorer the drug content homogeneity within DPI formulations, which is expected to negatively affect budesonide dose delivery during inhalation. Also, higher amounts of budesonide were deposited on throat airway region for lactose particles with smaller size which is likely to maximize the potential of local side effects including irritations and infections. Furthermore, higher amorphous lactose content and poorer flowability were observed for DPI formulations containing lactose particles with smaller size, which is expected to be disadvantageous in terms of DPI formulation stability, dose metering and processing at handling scale. In conclusion, despite that using lactose particles with smaller size can considerably enhance drug aerosolisation efficiency from DPIs; other limitations should be taken into account including higher side effects potency, higher dose variability, less stability and poorer flowability.