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Characterisation of aerosol delivery devices and their influence on deposition in humans and animals

thesis
posted on 2024-09-02, 23:05 authored by Ola Nerbrink

One way of administrating pharmaceutical drugs in the development phase and in the clinical situation is by inhalation. It is essential to ensure an accurate delivered dose, as the prediction of the effect and side effects of the drug action is dependent on a precise estimation of the given dose. During inhalation as compared to other techniques (oral or intravenous) this becomes more complicated as the dose is dependent on device performance and patient interaction during inhalation, both which influence the site of deposition which can be of interest for specific drug applications. This thesis will try to explain some of the main underlying factors involved, and how to control, or measure, the effect of them in order to achieve a more accurate dosing to patients.

Initially six different commercially available nebulisers were investigated in order to try to explain the nebuliser droplet generation and separation properties. The results obtained in this study indicate that the mass median diameters (MMD) of the investigated nebulisers were dependent on air velocity, and the ratio of liquid to air volumetric flow rate (QI/Qa). It was also found that changes in air velocity affects QI/Qa, and both air velocity and QI/Qa separately influence the size distribution and thus the output A novel inhalation system, called FIDO, was developed to enable a more accurate estimate of the inhaled dose than previously used methods. The data obtained supports the hypothesis that FIDO is more accurate in delivering and estimating a predefined inhaled dose compared to conventional indirect filter methods used today.

The effect of turbulence on regional deposition of Evans Blue dye tracer aerosol in normal and constricted airways was investigated using an animal (rabbit) model. This was achieved by using different aerosol carrier gases consisting of either Helium-Oxygen (80% He/ 20% 02) or air (79% N2/21% 02) in histamine-provoked and non-provoked rabbits. The results showed that bronchial provocation gave more central deposition (0.55 ± 0.11 expressed as ratio central/total deposition) compared to the non-provoked control group (0.80 ± 0.09). The He-O2 ventilated rabbits also had a significantly higher peripheral deposition compared with air ventilated rabbits when provoked.

The effect of the relative humidity of entrained ambient air on nebulised aerosol size properties was assessed in a study where two jet nebuliser designs were investigated using the proposed CEN standard. The first one was a conventional constant output nebuliser, the second one a breath enhanced nebuliser. The study showed a droplet size distribution dependency related to the relative humidity (RH) of the entrained air when using the conventional nebuliser, an effect which was not apparent for the breath enhanced nebuliser.

An inhalation study using sodium chromoglycate was performed on light to moderate asthmatic children. The effect on deposition was investigated by changing the droplet size distribution inhaled through alteration of the relative humidity (RH) (low RH corresponding to 13% and a high RH corresponding to >90% RH) of the entrained air. The droplet size was monitored with an impactor and was found to be 1.2 mm for the low RH and 2.0 mm for the high RH. A difference in the total deposition between the low and high RH, 34% and 41% respectively, was found. The results were compared with the results obtained by a lung deposition software, TGLD2, developed at Karolinska Institute. The software could differentiate between lung and extrathoracic deposition and could explain the difference in the total deposition obtained at different RH. The study also showed a correlation between the tidal volume inhaled and the total amount deposited. There was also a correlation between the RH (e.g. droplet size) and the amount deposited.

List of scientific papers

I. Nerbrink O, Dahlback M, Hansson HC (1994). "Why do medical nebulizers differ in their output and particle size characteristics? " J Aerosol Med 7(3): 259-76
https://pubmed.ncbi.nlm.nih.gov/10150483

II. Nerbrink O, Fagerstrom PO, Wendel T, Eirefelt S, Kallen A, Marchner H, Dahlback M (1997). "A novel dry powder aerosol delivery system for real time measurment of the inhaled dose of large animals (dogs)." J Aerosol and Technol 27: 141-61

III. Svartengren M, Skogward P, Nerbrink O, Dahlback M (1998). "Regional deposition of inhaled Evans blue dye in mechanically ventilated rabbits with air or helium oxygen mixture. " Exp Lung Res 24(2): 159-72
https://pubmed.ncbi.nlm.nih.gov/9555574

IV. Nerbrink O, Dennis JH, Pieron C, Pagels J (2001). "Effect of humidity on constant output and breath enhanced nebuliser designs." Aerosol Technology (Submitted)

V. Nerbrink O, Lindstrom M, Svartengren M (2001). "Inhalation and deposition of nebulised sodium chromoglycate in two different particle size distributions in young subjects with asthma." Pulm Ped (Submitted)

History

Defence date

2001-05-18

Department

  • Department of Global Public Health

Publication year

2001

Thesis type

  • Doctoral thesis

ISBN-10

91-628-4753-8

Number of supporting papers

5

Language

  • eng

Original publication date

2001-04-27

Author name in thesis

Nerbrink, Ola

Original department name

Department of Public Health Sciences

Place of publication

Stockholm

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