In patients using pressurized metered-dose inhalers (pMDI) for asthma, inhalation technique was improved via innovative training tools providing audio-visual feedback to patients on correct technique. The use of these app-based devices – namely, the Clip-Tone and the Flo-Tone CR – resulted in better lung deposition of salbutamol, according to study findings published recently in the Journal of Drug Delivery Science and Technology.

Poor technique using pMDIs — especially forceful inhalation — leaves the patient with subpar delivery of drugs to the lungs, leading to worse outcomes among adults with asthma. Researchers sought to evaluate the impact of pMDI add-on devices, namely the Clip-Tone and the Flo-Tone CR, which both are linked to a smartphone app. As the researchers explained, these add-on devices “produce a whistling sound corresponding to the flow of air while [patients are] trying to maintain a slow inhalation. The sounds produced are recognized by their related smartphone applications and the number of seconds of the inhalation process is shown on the smartphone screen giving immediate feedback.”

The researchers conducted an investigational cross-over study that included 12 healthy adult volunteers (31.1±10.49 years of age; 73.3±14.48 Kgs weight; 50% female). Each participant performed inhalation via the pMDI alone and then performed inhalation via the pMDI with the add-on Clip-Tone tool and the add-on Flo-Tone CR tool (in randomized order) with 48 hour washout periods between the inhalation procedures.  completions.

Continue Reading

The investigators found that the inhalation duration for Clip-Tone was (5.22±1.07 seconds), similar for Flo-Tone CR, and unreported for the pMDI alone. Urine samples were taken at 30 minutes to represent lung deposition of salbutamol and at 24 hours to represent systemic bioavailability using the urinary salbutamol excretion pharmacokinetic (in-vivo) model.

Mean measurements revealed a significant increase (P <.01) in salbutamol in urine pMDI + Clip-Tone (22.2±8.21), and pMDI + Flo-Tone CR (19.83±9.94) compared with using pMDI alone (10.68±5.82). The urine sample at 24 hours revealed no significant difference in salbutamol levels between the 3 groups. Inhalation duration showed a high positive correlation with salbutamol in urine at 30 minutes (r = 0.72; P <.001). Half of study participants said they preferred the Clip-Tone add-on tool; half said that both tools were similar, and none of the participants chose Flo-Tone CR as their first choice.

The researchers concluded that, “Using advanced training tools that provide audio-visual feedback improved the inhalation technique compared to the sole use of pMDI, which was translated into improved lung deposition of salbutamol.” They added that the Clip-Tone device did not show superiority in lung deposition of salbutamol compared with the Flo-Tone CR device.

Study limitations include age bias, underpowered sample size, lack of randomization for the order of tools used, and the inability to measure duration of inhalation in the pMDI alone.


Sobh AHM, Rabea H, Hamouda MA, Shawky F, Saeed H, Abdelrahim MEA. The impact of using different add-on devices to pressurized metered-dose-inhalers containing salbutamol in healthy adult volunteers: An in-vivo study. J Drug Deliv Sci Technol. Published online June 23, 2022. doi:10.1016/j.jddst.2022.103539

This article originally appeared on Pulmonology Advisor