Performance of Low Air Volume Dry Powder Inhalers (LV-DPI) when Aerosolizing Excipient Enhanced Growth (EEG) Surfactant Powder Formulations

Efficient delivery of dry powder aerosols dispersed with low volumes of air is challenging. This study aims to develop an efficient dry powder inhaler (DPI) capable of delivering spray-dried Survanta-EEG powders (3-10 mg) with a low volume (3 mL) of dispersion air. A series of iterative design modifications were made to a base low air volume actuated DPI. The modifications included the replacement of the original capsule chamber with an integral dose containment chamber, alteration of the entrainment air flow path through the device (from single-sided (SS) to straight through (ST)), change in the number of air inlet holes (from one to three), varying the outlet delivery tube length (45, 55, and 90 mm) and internal diameter (0.60, 0.89, and 1.17 mm). The modified devices were evaluated by determining the influence of the modifications and powder fill mass on aerosol performance of spray-dried Survanta-EEG powders. The optimal DPI was also evaluated for its ability to aerosolize a micronized powder. The optimized dose containment unit DPI had a 0.21 mL powder chamber, ST airflow path, three-0.60 mm air inlet holes, and 90 mm outlet delivery tube with 0.89 mm internal diameter. The powder dispersion characteristics of the optimal device were independent of fill mass with good powder emptying in one 3 mL actuation. At 10 mg fill mass, this device had an emitted mass of 5.3 mg with an aerosol Dv50 of 2.7 mu m. After three 3 mL actuations, >85% of the spray-dried powder was emitted from the device. The emitted mass of the optimal device with micronized albuterol sulfate was >72% of the nominal fill mass of 10 mg in one 3 mL actuation. Design optimization produced a DPI capable of efficient performance with a dispersion air volume of 3 mL to aerosolize Survanta-EEG powders.