The impact of using different add-on devices to pressurized metered-dose-inhalers containing salbutamol in healthy adult volunteers: An in-vivo study

Abstract

BackgroundImproper handling of pMDIs results in suboptimal delivery of the drug to the lungs and poor clinical outcomes in adult asthmatics. Forceful inhalation is one of the most critical errors in the pMDI inhalation technique. Using advanced tools to optimize the inhalation technique is required to enhance the inhalation flow and hence the drug delivery to the lungs. MethodsTwo newly adopted add-on devices; the Clip-Tone and the Flo-Tone CR, along with their respective smartphone applications were tested and compared to the normal pMDI inhalation. 12 healthy volunteers (6 females) were trained to use the pMDI alone, pMDI + Clip-Tone, and pMDI + Flo-Tone CR in a cross-over study design. Using the urinary salbutamol excretion pharmacokinetic model, urine samples of 30 min (USAL0.5) and collective urine of 24 h (USAL24) were collected for each experiment; the first represents the lung deposition and the latter represents the systemic bioavailability. Samples were solid-phase extracted and then assayed using HPLC to determine the amount of salbutamol in urine. Since subjects were trained to perform through 2 different add-on tools in addition to the pMDI alone, they reported their personal preference regarding the delivery method. Also, a correlation between inhalation time to USAL 0.5 was determined. ResultsComparing means (SD) of USAL0.5 among the 3 groups, pMDI + Clip-Tone, 22.2 (8.21), and pMDI + Flo-Tone CR, 19.83 (9.94), showed a significant increase (p < 0.01) compared to using pMDI alone, 10.68 (5.82). Comparing means (SD) of USAL24, no significant difference was found among salbutamol amounts in the urine of the pMDI + Clip-Tone group, 54.77 (20.18), and pMDI + Flo-Tone CR group, 49.76 (25.30), and pMDI sole use group, 56.48 (24.42). Studying the associations between the inhalation duration measured and the amount of salbutamol in urine after 30 min, there was a significantly high positive correlation (r = 0.72) (p < 0.001). 50% of the subjects preferred training using the Clip-Tone add-on tool while the other half felt comfortable using both add-on tools. ConclusionUsing 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. The more preferred add-on tool by subjects, the Clip-Tone device, has not shown significant superiority to the Flo-Tone CR in terms of lung deposition of salbutamol.