In vivo deposition study of a new generation nebuliser utilising hybrid resonant acoustic (HYDRA) technology

• Published in: International journal of pharmaceutics Vol. 580; p. 119196
• Main Authors: Kwok, Philip Chi Lip, McDonnell, Amarin, Tang, Patricia, Knight, Callum, McKay, Erin, Butler, Sidney P., Sivarajah, Allen, Quinn, Renee, Fincher, Luke, Browne, Effie, Yeo, Leslie Y., Chan, Hak-Kim
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.04.2020
• Subjects: 99mTc-DTPA; Administration, Inhalation; Adult; Aerosol; Aerosols - administration & dosage; Aerosols - metabolism; Deposition; Female; Humans; HYDRA; In vivo; Lung - diagnostic imaging; Lung - drug effects; Lung - metabolism; Lungs; Male; Nebuliser; Nebulizers and Vaporizers; Radiolabel; Single Photon Emission Computed Tomography Computed Tomography - methods; Sound; SPECT/CT; Surface acoustic wave; Technetium Tc 99m Pentetate - administration & dosage; Technetium Tc 99m Pentetate - metabolism; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; Tissue Distribution - drug effects; Tissue Distribution - physiology; Tomography, Emission-Computed, Single-Photon - methods; Young Adult; HYDRA; FEF25–75; Nebuliser; PEFR; Aerosol; Surface acoustic wave; SPECT/CT; In vivo; FVC; Lungs; Radiolabel; FEV1; Deposition; 99mTc-DTPA; (99m)Tc-DTPA
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119196

[Display omitted] Conventional nebulisation has the disadvantages of low aerosol output rate and potential damage to macromolecules due to high shear (jet nebulisation) or cavitation (ultrasonic nebulisation). HYDRA (HYbriD Resonant Acoustics) technology has been shown to overcome these problems by using a hybrid combination of surface and bulk sound waves to generate the aerosol droplets. We report the first in vivo human lung deposition study on such droplets. Twelve healthy adult subjects inhaled saline aerosols radiolabelled with technetium-99 m complexed with diethylene triamine penta-acetic acid (99mTc-DTPA). The distribution of the aerosolised droplets in the lungs was imaged by single photon emission computed tomography combined with low dose computed tomography (SPECT/CT). The volume median diameter and geometric standard deviation of the droplets were 1.32 ± 0.027 µm and 2.06 ± 0.040, respectively. The mean delivery efficiency from the nebuliser into the body was 51.2%. About 89.1 ± 4.3% and 2.3 ± 1.4% of the inhaled radiolabelled dose deposited in the lungs and oropharynx, respectively. The deposition was symmetrical and diffusive between the two lungs, with a mean penetration index of 0.82. Thus, the prototype HYDRA nebuliser showed excellent in vivo aerosol deposition performance, demonstrating its potential to be further developed for clinical applications.