Is driving gas flow rate clinically important for nebulizer therapy?

Hadfield, J W; Windebank, W J; Bateman, J. R. M.

doi:10.1016/0007-0971(86)90009-4

Cited by 19 publications

(5 citation statements)

References 10 publications

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“…The same change in DGF produced a larger increase in quantity of drug depositing upon the filter of 79% when the tidal volume was set at 400 ml. The dose deposited upon the filter increased from 2-09 mg (0-1-98-1 [22) to 3-74 mg (3-57-3-94). The dose deposited on the filter when nebulising 4 ml of a 0 5% solution of sodium cromoglycate for five minutes was 0-57 mg (0-53-0-59) when using a DGF of 81/minute and a tidal volume of 50 ml.…”

Section: Resultsmentioning

confidence: 99%

Drug delivery from jet nebulisers.

Everard

Clark

Milner

1992

Archives of Disease in Childhood

143

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Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may aliow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery was studied by constructing a model to simulate the respiratory pattern of individuals with different tidal volumes using a Starling ventilator and filter. Sodium cromoglycate was nebulised under a variety of operating conditions and the dose deposited on the filter was assayed. Tidal volumes of 50 and 400 ml were used at a frequency of 32 breaths per minute.Increasing the DGF from 4 to 8 I/minute produced a 264% increase in the rate of drug output but only a 32% increase in aerosol concentration. The mass of drug contained within droplets <5 ,tm increased from 26*8% to 70-8% of the total. The resultant increase in rate of drug delivery to the filter was 34% for a tidal volume of 50 ml and 79% for a tidal volume of 400 ml though the dose contained within droplets <5 itm increased by 4-fold at 50 ml tidal volume and by more than 5-fold at the higher tidal volume. Halving the solution concentration halved the rate of drug delivery. Increasing the tidal volume 8-fold from 50 to 400 ml resulted in an increase in the rate of drug deposition upon the filter of only 2.2 to 3-fold depending upon the DGF so that substantially more drug per ml inhaled was delivered at the lower tidal volume.These results are explained by considering factors that influence the rate of drug delivery. At low tidal volumes the rate of drug delivery at a given respiratory rate is dependent on the tidal volume and aerosol concentration. At high tidal volumes it is dependent upon aerosol concentration and volume of available aerosol and is essentially independent of tidal volume.

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Section: Resultsmentioning

confidence: 99%

Drug delivery from jet nebulisers.

Everard

Clark

Milner

1992

Archives of Disease in Childhood

143

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“…Studies by Hadfield et al (1986) and Douglas et al (1986), failed to demonstrate a significant change in clinical response upon changing droplet size. However, in each of these studies only the upper respiratory tract response was investigated.…”

Section: Discussionmentioning

confidence: 96%

“…Despite the fact that the production of a small droplet size is used as an indicator of an efficient nebuliser, there are relatively few studies that demonstrate clear clinical benefits o f producing smaller droplet size. Certain studies fail to show any correlation between droplet size and clinical response (Douglas et al, 1986;Hadfield et al, 1986). However, this may be due to inter-patient variability in breathing pattern (Pavia et al, 1977), or to the polydispersity of the aerosols.…”

Section: Factors Influencing the Droplet Size Produced From Ultrasonic Nebulisersmentioning

confidence: 99%

Nebulisers for the generation of liposomal aerosols

Bridges

Taylor

1998

International Journal of Pharmaceutics

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The thesis details investigations into the use of various types of medical nebuliser for the generation of liposomal aerosols. Chapter 1 provides a comprehensive introduction to the theory and practice of drug delivery to the respiratory tract. It also reviews the potential applications of inhaled liposomes to drug delivery, and the devices used to generate liposomal aerosols.A preliminary investigation into the physicochemical attributes of liposomes which may. influence aerosol generation is detailed in chapter 2. These include studies of the stability of liposome bilayers to disruptive energy (ie. membrane extrusion and sonication), investigations of the surface tension and viscosity of liposomes, and also the release of a liposomally entrapped hydrophilic marker. Chapter 3 demonstrates how these physicochemical attributes may influence nebulised liposomal aerosols. Most notably, the aerosol droplet size and output rate are proportional to the concentration of the formulation.The residual liposome concentration is determined by the mean liposome size. The droplet size, nébulisation time, aerosol output, and residual liposome concentration are all significantly influenced by the particular jet nebuliser model selected for aerosol generation. The relative stability of different liposome formulations to nébulisation is also determined by a variety of factors, as revealed in chapter 4 of the thesis. The release of an entrapped marker, and the reduction in liposome size during nébulisation, is influenced by the nebuliser model, and also the liposome size and bilayer composition.Chapter 5 investigates the freeze drying of liposomes. The chapter concludes that liposomes for nébulisation may be freeze dried in the presence of a cryoprotectant, without influencing the aerosol produced following subsequent rehydration. Chapter 6 reveals that the droplet size produced from ultrasonic nebulised liposomes is relatively large, and the output inefficient from concentrated formulations. In addition, ultrasonic nébulisation is associated with similar liposome stability concerns as jet nébulisation.

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“…[63][64][65][66][67][68][69][70][71][72][73] These studies generally provided limited APSD data (eg, MMAD and geometric standard deviation, or FPM). Many of these studies involved bronchodilator aerosols in crossover studies in small (G20) groups of 57 FEV 1 indicates forced expiratory volume in 1 second; pred, predicted; FPF, fine particle fraction.…”

Section: Other Inhaler Datamentioning

confidence: 99%

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CIgenerated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

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Is driving gas flow rate clinically important for nebulizer therapy?

Cited by 19 publications

References 10 publications

Drug delivery from jet nebulisers.

Drug delivery from jet nebulisers.

Nebulisers for the generation of liposomal aerosols

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

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