El-Gendy 2014

Novel Delivery System for Administering Budesonide NanoCluster Dry Powder Aerosols using a Mechanical Ventilator

Nashwa El-Gendy1, Warangkana Pornputtapitak1, Caitlin Uyemura2, Parthiban Selvam1, Joel Mermis3, Amy O’Brien Ladner3 and Cory Berkland1,2

1Department of Pharmaceutical Chemistry and 2Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, Kansas, 66047; 3 Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Kansas Medical center, Kansas City, Kansas 66160

PURPOSE. Clinical results for nebulized therapeutics to mechanically ventilated patients are highly variable and long dosing times are often required. Nebulized formulas suffer from ‘rain-out’ (condensation of aerosol droplets containing drug). A key to successful delivery is maintaining aerosol as a fine droplet or particle through ventilator tubing all the way to the distal end of tracheal tubing. An engineered budesonide NanoClusters successfully passed through endotracheal tubes whereas traditional dry powder formula failed. Here, a novel delivery system “AeroVent” composed of dry powder inhaler (DPI) attached to a catheter was designed to efficiently deliver therapeutic formulas to mechanically ventilated patients.

METHODS: Different capsule-based dry powder inhaler (DPI) devices were designed and fabricated by varying the mesh size and the inlet/outlet opening size. The novel designs were evaluated using device air resistance measurements and aerosol impaction techniques. The performance of Bud-NC dry powder was studied using the novel DPIcatheter system. The DPI was fitted to a catheter and explored as a unique system to bypass highly variable ventilator environment by delivering a fine Bud-NC aerosol through the catheter inserted in the endotracheal tube (Figure 1). Variables such as inhalation volume, ventilator flow rate, and catheter dimensions were explored. The results were accessed by one-way ANOVA followed by Tukey’s Multiple Comparison Test.

RESULTS: The resistance of the devices was not significantly different upon increasing the mesh size from 0.15 mm to 1.00 mm; however, the resistance increased when the inlet opening decreased from 2.5 mm to 1.5 mm. Surprisingly, the %EF (~90%) of NanoClusters delivered through these devices was not significantly different when the airflow was provided by negative pressure suggesting efficient performance of the Bud- NC powder itself. Variables were optimized to consistently deliver Bud-NC while minimizing sensitivity to ventilator settings. AeroVent circumvented the humid environment of the ventilator circuit and effectively aerosolized ~65% of fine budesonide powder (particle size <5 μm).

CONCLUSION: ‘NanoCluster’ particle engineering technology offers a unique and simple method to create high performance, excipient-free dry powder aerosols. The original DPI-catheter system “AeroVent” allowed placement, drug delivery and removal without disturbing the ventilator circuit, similar to procedures used for suctioning endotracheal tubes. As a platform technology for delivering engineered dry powder aerosols to ventilated patients, the novel system has a large market potential spanning multiple classes of drugs. The efficient and reproducible dosing of therapeutic amounts of Bud-NC suggests clinical utility of this delivery system. AeroVent combined with NanoCluster formulation technology has the potential to dramatically improve the convenience and effectiveness of drug delivery to ventilated patients in critical care.