Evaluation of patients' real-world post-dispensing use and storage environments of tiotropium bromide Respimat® soft mist inhaler on its in vitro dose delivery and lung deposition.

ABSTRACT

BACKGROUND: Oral inhalation is the main drug delivery route for treating obstructive lung conditions. Thus, many inhaler devices with various design and pharmaceutical formulation have been introduced. The fine particle dose (FPD) and mass median aerodynamic diameter (MMAD ≤ 5 µm) of the aerosol delivered dose (DD) dictate the therapeutically effective peripheral lung deposition. This study evaluated the in vitro aerosol emission performance of tiotropium bromide emitted from Spiriva® Respimat® soft mist inhalers (R) after living under patients' real-world, post-dispensing handling environments. METHODS: This was a two-stage investigation. In the first clinical stage, research ethical approval was obtained to enrol patients already been using R for at least 3 months. Those who signed consent were given both new R to use and temperature and relative humidity (RH) handheld, portable data loggers to keep in the vicinity of the given R. The participants returned the given R and data loggers after 2 weeks. Patient recruitment took place in Amman, Jordan, during the summer (RS) and winter (RW). Subsequently, in the second laboratory stage, other R were strictly stored at an average of 21.0 °C and 46.9% RH as control (RC). The Next Generation Impactor (NGI) was used to evaluate the RS, RW and RC. The NGI was operated at a flow rate of 30 L/min. RESULTS: The RS were exposed to an average (range) 23.6 °C (18.2-37.5 °C) and 43.8% RH (21.4-60.0% RH) that were statistically comparable (p > 0.05) to that of the RW; 17.3 °C (13.2-26.7 °C) and 52.8% RH (26.3-69.1% RH). The RW and RC retention environments were statistically different (p < 0.05), whilst the RS and RC had comparable (p > 0.05) conditions. No significant differences (p > 0.05) were found in the tiotropium bromide DD (2.39 vs 2.43 µg), FPD (0.88 vs 0.90 µg) and MMAD (5.1 vs 4.98 µm) between the RS and RW, respectively. Compared to the RC inhalers, both the RS and RW devices had significantly higher FPD and relatively smaller tiotropium bromide particles. CONCLUSIONS: Using the R under the fluctuating summer and winter environments of our patients would not affect its overall tiotropium bromide emission performance. The significant increase in the respirable mass of the RS and RW might be offset by the increase in particles <1 µm particularly in patients with poor inhaler technique.