El-Gendy 2013

Development of Budesonide NanoCluster Dry Powder Aerosols

Nashwa El-Gendy1 , Shan Huang1 , Parthiban Selvam1 , Pravin Soni2 and Cory Berkland1 1University of Kansas, 2 PharMacro, LLC

PURPOSE. Delivery of drugs to the lungs as an aerosol offers exciting new product opportunities for local or systemic therapy. The objective of this study was to formulate dry powder aerosols using controlled nanoparticle agglomeration technology. Nanoparticles of budesonide were controllably assembled in suspension to form low density agglomerates. METHODS. Wet milling process for producing agglomerated budesonide nanoparticles (i.e. ‘NanoClusters’) was explored. Parameters such as milling time and drug concentration were investigated and the aerosol performance of dried NanoClusters was characterized using an Aerosizer, a Fast Screening Impactor (FSI) and an Andersen Cascade Impactor (ACI). The reproducibility of NanoCluster processing and aerosol performance was established. The physical stability of a selected budesonide NanoCluster formulation was investigated using industry standard dose content uniformity and cascade impaction techniques. The chemical stability of the lead formulation was also determined as a function of processing parameters and storage conditions. RESULTS. Wet milling produced budesonide NanoClusters (NC) within 10 h. The NanoClusters were agglomerates of drug nanoparticles (~300 nm) with a mean aerodynamic diameter between 1 and 3 μm capable of deep lung penetration. The process was indeed highly reproducible, as estimated from the mean particle sizes of the three batches. High emitted fraction (~70%) and a large fine particle fraction (~70% <5.7 m at 28.3 L/min) suggested that the NanoCluster formulations would offer highly efficient delivery of drug throughout the lung. Stored dry powder maintained the original bulk chemical and physical properties. Budesonide NanoClusters maintained excellent aerosol performance even after 1 year of storage. CONCLUSIONS. New processes for engineering particles are sought after for improving the efficiency of aerosol delivery and for facilitating drug penetration to the lung periphery. Wet milling technique was able to produce aerosol particles composed entirely of budesonide. High emitted fraction and large fine particle fraction suggested that budesonide NanoClusters would offer highly efficient delivery of drug throughout the lung to improve treatment of peripheral lung diseases such as chronic obstructive pulmonary disease (COPD). This study also confirms the reproducibility and robust stability of NanoCluster powders as a novel means to turn drug particles into high performance aerosols.