Quantitative analysis and design of a spray aerosol inhaler. Part 2: improvements in mouthpiece performance.

The objective of this study was to utilize previously identified critical design attributes for the capillary aerosol generator as a model spray inhaler in order to develop a second-generation device that minimized aerosol drug deposition in the mouthpiece. Computational fluid dynamics (CFD) predictive analysis of the critical design attributes indicated that turbulence intensity should be reduced and the effective mouthpiece diameter should be increased. Two second-generation inhaler mouthpieces meeting these specifications were manufactured and tested. The first device (Design 1) implemented a larger cross-sectional area in the mouthpiece and streamlined flow, whereas the second device (Design 2) used a perforated mouthpiece wall. An in vitro deposition study was performed to quantify the deposition of drug mass in the mouthpieces and connected induction ports, and the results were compared with the CFD predictions. The two second-generation mouthpieces reduced in vitro aerosol deposition from the original value of 7.8% to values of 2.1% (Device 1) and 4.3% (Device 2), without largely altering the induction port deposition. This was achieved by design alterations aimed at reducing turbulence intensity and increasing the effective mouthpiece diameter. CFD model predictions were in good agreement with the in vitro experimental data. A second-generation spray inhaler mouthpiece with low drug deposition was developed using a predictive CFD model and in vitro experiments. Applying this quantitative analysis and design methodology to medical devices, which is similar to the Quality by Design paradigm, could provide significant advantages compared with traditional approaches.