Effects of flow lamination on aerosolized drug delivery through spatial barriers

Abstract

In this study we evaluated the effects of flow lamination on aerosol flow dynamics and deposition at the exit point in testing models with spatial barriers (narrowing or curving).We compared ModiFlow (MF) to an idealized Standard Spacer (SS) in their efficiency of delivery of aerosolized medication (fluticasone) across different types of spatial barriers. Fluticasone propionate HFA Inhaler from Prasco Labs 220 µg per actuation was used to deliver 1 spray in each test tube. To compare the efficiencies of aerosol delivery for MF vs a SS, which was defined as the amount of aerosolized medication delivered to the target surface area from a pre-defined total amount sprayed into each spacer, four different Test Tubes (TT) have been used. At the distal end one of the 4 types of spatial barriers was mounted - abrupt cross-sectional narrowing by 60 % or 80 %, or gradual 60- or 90-degree curving. To closely mimic physiological drug delivery conditions, we also assessed the deposition of aerosolized drugs using a 3D oral mucosal tissue. Quantification of fluticasone deposition on oral mucosal tissues and Petri dishes was done by Mass spectrometry. Particle size distribution and Spray Pattern Testing was done by Aerosol Research and Engineering Labs Inc. The results of the experiments have clearly demonstrated a significant advantage of MF over SS in all settings across different types of spatial barriers (narrowing and curving). However, the results are more impressive for delivery across different types of spatial barriers at a long distance (20 cm) - in some instances 10-72 times more fluticasone being delivered to the target via MF in comparison with the SS, whereas for short distance (5 cm) more modest improvements are achieved by using MF (1.2 - 3 times). The aerosol drug delivery advantage of MF over SS was more pronounced at a distance of 20 cm, but it remained significant even at 5 cm. MF demonstrated a more efficient aerosol plume geometry and particle distribution, resulting in a more coherent and less turbulent flow, particularly at the 5 cm distance from the exit compared to SS. MF has significantly outperformed the idealized SS in efficiency of delivery of aerosolized fluticasone to distant targets via pathways with two types of spatial barriers - narrowing or curving. This may indicate a better performance under conditions of complex spatial barriers in real human airways.

Keywords: Aerosol; Barrier; Fluticasone; Lamination; ModiFlow (MF); Plum geometry; Standard Spacer (SS); Turbulance.