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.
KEY WORDSmass median plume angle plume geometry albuterol sulfate plume induction port evaluator high-speed laser imaging
High-speed laser imaging
Mass Median Plume Angle
Plume Induction Port Evaluator
Daniel Moraga-Espinoza would like to thank CONICYT-Becas Chile for the scholarship to pursue his doctoral studies.
Compliance with Ethical Standards
Conflict of Interest
The author (HDCS) of this paper consults for and has equity ownership in Respira Therapeutics and Nob Hill Therapeutics on inhaled product development. The terms of this arrangement have been reviewed and approved by the University of Texas at Austin in accordance with its policy on objectivity in research.
- 1.Chen Y, Young PM, Murphy S, Fletcher DF, Long E, Lewis D, et al. High-speed laser image analysis of plume angles for pressurised metered dose inhalers: the effect of nozzle geometry. AAPS PharmSciTech. 2017;18(3)782–9.Google Scholar
- 16.Ohrn T, Senser DW, Lefebvre AH. Geometric effects on spray cone angle for plain-orifice atomizers. Atomization Sprays. 1991;1(3):253–68.Google Scholar
- 21.Versteeg H, Hargrave G, Harrington L, Shrubb I, Hodson D, editors. The use of computational fluid dynamics (CFD) to predict pMDI air flows and aerosol plume formation. Respiratory Drug Delivery. 2000;1:257–64.Google Scholar
- 25.FDA. Draft guidance on budesonide; formoterol fumarate dihydrate. Silver Spring: US Food and Drug Administration; 2015.Google Scholar