Effect of Inhalation Flow Rate on Mass-Based Plume Geometry of Commercially Available Suspension pMDIs.

Although high-speed laser imaging is the current standard to characterize the plume angle of suspension-based pressurized metered dose inhalers (pMDIs), this method is limited by the inability to identify the drug content in a droplet and simulate inhalation flow. The Plume Induction Port Evaluator (PIPE) is a modified induction port for cascade impactors that allows for the calculation of the angle of a plume based on direct drug mass quantification rather than indirect droplet illumination under airflow conditions. The objective of this study was to investigate the use of the PIPE apparatus to evaluate the effect of airflow on the Mass Median Plume Angle (MMPA) of commercially available suspension-based pMDIs (Ventolin® HFA, ProAir® HFA, and Proventil® HFA). Deposition patterns within PIPE were log-normally distributed allowing for the calculation of the MMPA for the three suspension products. Mass-based plume angles were significantly smaller (narrower angle) when inhalation airflow was used compared to no flow conditions (reduction of MMPA was 8, 16, and 13% for Ventolin® HFA, ProAir® HFA, and Proventil® HFA, respectively). Additionally, new parameters for characterizing plume geometry were calculated (MMPA ex-actuator and plume orientation). Mass-based plume angles of the suspension-based pMDI formulations were highly reproducible and demonstrated the effect of inhalation flow rate. These results suggest that plume geometry tests should be evaluated under flow conditions which is not possible using current methodologies. Graphical Abstract ᅟ.

Development, Characterization, and In Vitro Testing of Co-Delivered Antimicrobial Dry Powder Formulation for the Treatment of Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is an opportunistic bacteria responsible for recurrent lung infections. Previously, we demonstrated that certain materials improved the activity of tobramycin (Tob) against P. aeruginosa biofilms in vitro. We aimed to develop prototype dry powder formulations comprising Tob and a mixture of excipients and test its aerodynamic properties and antimicrobial activity. First, we evaluated different combinations of excipients with Tob in solution against P. aeruginosa biofilms. We selected the compositions with the highest activity, to prepare dry powders by spray drying. The powders were characterized by morphology, bulk density, water content, and particle size distributions. Finally, the antimicrobial activity of the powders was tested. The combinations of Tob (64 µg/mL) with l-alanine and l-proline (at 10 and 20 mM; formulations 1 and 2, respectively) and with l-alanine and succinic acid (at 20 mM; formulation 3) showed the highest efficacies in vitro and were prepared as dry powders. Formulation 1 had the best aerodynamic performance as indicated by the fine particle fraction and the best in vitro activity against P. aeruginosa biofilms. Formulation 3 represents a good candidate for further optimization because it demonstrated good dispersibility potential and optimization of the particle size distribution may achieve high delivery efficiencies.