Engineered Dry Powder Budesonide Particles for Improved Pediatric Inhalation Therapy

Abstract

Corticosteroids have been the cornerstone treatment for asthma; however, several challenges exist with current inhaled steroids for pediatric patients. Dry powder corticosteroids are now being prescribed to pediatric patients 蠅 6 years of age with some success; however, many younger patients lack the inhalation energy required to properly fluidize and deagglomerate the drug particles, which leads to improper drug delivery, increases oral steroid exposure, and reduces long term compliance. We tested the hypothesis that engineered budesonide NanoClusters, drug particles with decreased density per surface area, would improve fluidization and deagglomeration efficiency compared to commercially available micronized budesonide and Pulmicort™ powders at flow rates seen in pediatric patients. Micronized budesonide powder was wet milled into micron sized NanoClusters using a Netzsch MiniCer Media Mill and then lyophilized. Budesonide powders were tested at various flow rates in a custom fabricated electronically controlled flow rate adjustable pneumatic device coupled to an Anderson Cascade Impactor. NanoCluster budesonide achieved EFmax (~85%) at a flow rate of 2.5 L/minute, whereas EF of micronized budesonide and Pulmicort™ were only minimally emitted (~2‐3%) at this flow rate. Importantly, fine particle fraction (FPF) of NanoClusters was significantly elevated compared to micronized budesonide and Pulmicort™ formulations. The data suggests that NanoCluster formulation improves budesonide dispersion properties at low flow rates, potentially allowing a lower unit dose formulation of budesonide for children without altering the effective therapeutic dose; increasing overall therapeutic index.