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Beyond Small Particles: Development of DPIs that Target Small Airways and Alveoli

Longest P, Tian G, Behara S, Farkas DR, Son Y, Hindle M.

Respiratory Drug Delivery 2014. Volume 1, 2014: 183-194.

Abstract:

Decreasing the particle size of pharmaceutical aerosols improves lung penetration and increases delivery of medications to the small airways resulting in more effective treatments of lung diseases. Controlled condensational growth methods that modify the size of inhaled particles may further enhance the targeting of aerosols to the small airways. The objective of this study was to review the development and performance of new excipient enhanced growth (EEG) based dry powder inhalers (DPIs) and evaluate the lung delivery characteristics with an emphasis on deposition in the small tracheobronchial (TB) and alveolar airways. The combination of highly dispersible EEG powders together with new 3D rod array based DPIs produced extremely efficient aerosolization with fine particle fractions (FPFs) less than 5 μm above 90% and emitted mass median aerodynamic diameters (MMADs) below 1.5 μm. Changes in emitted dose (ED), FPF, and MMAD were negligible for pressure drops in the range of 2 to 6 kPa across the new inhalers. Mouth-throat (MT) depositional losses with these inhalers and formulations were also extremely low. Compared with current DPI products, these new devices reduce MT depositional losses by an order of magnitude, increase drug delivery to the lower TB airways by a factor of 10-fold, and improve alveolar delivery by a factor of approximately 3-fold based on a combination of in vitro experiments and numerical predictions. These improved aerosol delivery and targeting characteristics can enhance the clinical efficacy of drugs intended for treating the small airways.