Factors affecting the efficiency of aerosolized salbutamol delivery via a metered dose inhaler and equine spacer device

Abstract

Despite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered beyond the spacer. Although this aerosol had a high [89.6% (±2.4)] fine particle (<5 μm) fraction, and a low mass median aerodynamic diameter [2.52 (±0.29) μm], and particle size variability [geometric SD - 1.66 (±0.16) μm], within all particle size fractions, there was a high coefficient of variance (31-79%) of the percentage salbutamol delivered between experimental runs, thus impeding any effort to predict drug delivery to the patient during equine inhalation therapy. Despite observable trends and with the exception of minor statistically significant changes in the least abundant particle sizes, none of the deviations from a 'best practice' delivery technique significantly altered the relative salbutamol delivery beyond the spacer, a finding which has potential relevance with regard to maintaining user compliance.

Inhalation therapy for equine lower respiratory tract disease

“…With respect to the efficiency of salbutamol delivery, this study failed to demonstrate any significant detrimental effect of not shaking the MDI before each of the actuations (provided the device was shaken before the first actuation), not maintaining an optimal angle of MDI actuation within the spacer, and performing multiple rapid actuations in rapid succession, all factors which could significantly impact on the level of compliance of the user (Pirie and others 2016). …”

Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial

“…Currently, adoption of the inhaled route for corticosteroid administration to horses necessitates the “off‐label” use of either inhaled formulations licensed for humans (eg MDIs) or the nebulisation of corticosteroid preparations (eg dexamethasone) licensed for administration to horses via other (noninhaled) routes 15,17 . Unsurprisingly, inherent differences exist between the various methods currently adopted to deliver inhaled corticosteroids to horses, including aerosol particle size distribution, efficiency and consistency of drug deposition within the lower airways and ease of use 16,18 . Despite the cited benefits of inhaled corticosteroid administration in equine asthma, application of these “off‐label” treatment practices in horses still results in suppression of the hypothalamo‐pituitary‐adrenal axis (HPA) and a treatment‐associated reduction in blood cortisol levels, reflecting a level of systemic absorption of active drug from the site of deposition 12,19‐22 .…”

“… 15 , 17 Unsurprisingly, inherent differences exist between the various methods currently adopted to deliver inhaled corticosteroids to horses, including aerosol particle size distribution, efficiency and consistency of drug deposition within the lower airways and ease of use. 16 , 18 Despite the cited benefits of inhaled corticosteroid administration in equine asthma, application of these “off‐label” treatment practices in horses still results in suppression of the hypothalamo‐pituitary‐adrenal axis (HPA) and a treatment‐associated reduction in blood cortisol levels, reflecting a level of systemic absorption of active drug from the site of deposition. 12 , 19 , 20 , 21 , 22 Ciclesonide, a glucocorticoid licensed for the treatment of allergic rhinitis and chronic asthma in humans, 23 is a prodrug which is de‐esterified in the lung to the active metabolite desisobutyryl‐ciclesonide (des‐CIC).…”

Pressurized Metered-Dose (pMDI) Aerosol Spray Deposition in Large-and Medium-Volume Spacers

“…Furthermore, drug delivery from spacers have been assessed in the past using a variety of techniques including in vitro particle measurements, chemical assaying, pharmacokinetic studies, and radionuclide imaging studies [7,11,12,13,14]. This has created a broad array of testing protocols.…”