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

• Published in: Journal of drug delivery science and technology 2022-08, Vol.74, p.103539, Article 103539
• Main Authors: Sobh, Ahmed H.M., Rabea, Hoda, Hamouda, Manal Ali, Shawky, Farid, Saeed, Haitham, Abdelrahim, Mohamed E.A.
• Format: Article
• Language: English
• Subjects: Asthma; Clip-tone; Flo-tone CR; Inhalation technique; Pharmacokinetic model; Urinary salbutamol
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103539

Improper 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. Two 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. Comparing 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