In VitroDetermination of the Optimal Particle Size for Nebulized Aerosol Delivery to Infants

Abstract

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

Development of the Premature Infant Nose Throat-Model (PrINT-Model)—An Upper Airway Replica of a Premature Neonate for the Study of Aerosol Delivery

“…This finding is in good agreement with other studies using upper airway cast models (4,6,30). In an in vitro study by Schuepp et al (30), using the SAINT model and the same nebulizer-drug combination we used, lung doses, calculated as percentage of emitted dose, were in the range of 7.9 -42.3%.…”

Comparison of HFNC, bubble CPAP and SiPAP on aerosol delivery in neonates: An in‐vitro study

“…Nevertheless, further research is required to identify the safety and the efficacy of HHFNC in comparison to NCPAP. Schüepp et al (2005) conducted an in-vitro study to determine the optimal aerosol particle size for inhalation therapy in infants. They also examined the effect of breathing patterns and aerosol particle size on aerosol lung deposition using an infant upper airway lung model (Sophia Anatomical Infant Nose-Throat [SAINT] model).…”

Respiratory System Deposition with a Novel Aerosol Delivery System in Spontaneously Breathing Healthy Adults

“…While in vivo data are sparse, modeling of the upper airway in infants 31 would imply that the definition of the respirable fraction should be particles much smaller, perhaps Յ 3 m, 32 or even smaller. 33 This would be supported by the in vivo nuclear medicine deposition studies by Chua et al, 19 who compared deposition from the traditional unvented nebulizer over a large size range in infants and children with cystic fibrosis. Similar conclusions were reached in a deposition study in infants, using metered-dose inhalers with valved holding chambers.…”