PediatricIn VitroandIn SilicoModels of Deposition via Oral and Nasal Inhalation

Abstract

Respiratory tract deposition models provide a useful method for optimizing the design and administration of inhaled pharmaceutical aerosols, and can be useful for estimating exposure risks to inhaled particulate matter. As aerosol must first pass through the extrathoracic region prior to reaching the lungs, deposition in this region plays an important role in both cases. Compared to adults, much less extrathoracic deposition data are available with pediatric subjects. Recently, progress in magnetic resonance imaging and computed tomography scans to develop pediatric extrathoracic airway replicas has facilitated addressing this issue. Indeed, the use of realistic replicas for benchtop inhaler testing is now relatively common during the development and in vitro evaluation of pediatric respiratory drug delivery devices. Recently, in vitro empirical modeling studies using a moderate number of these realistic replicas have related airway geometry, particle size, fluid properties, and flow rate to extrathoracic deposition. Idealized geometries provide a standardized platform for inhaler testing and exposure risk assessment and have been designed to mimic average in vitro deposition in infants and children by replicating representative average geometrical dimensions. In silico mathematical models have used morphometric data and aerosol physics to illustrate the relative importance of different deposition mechanisms on respiratory tract deposition. Computational fluid dynamics simulations allow for the quantification of local deposition patterns and an in-depth examination of aerosol behavior in the respiratory tract. Recent studies have used both in vitro and in silico deposition measurements in realistic pediatric airway geometries to some success. This article reviews the current understanding of pediatric in vitro and in silico deposition modeling via oral and nasal inhalation.

Variability in nose-to-lung aerosol delivery

“…Several correlations exist in the literature that use a variety of parameters to characterize variability, including SA/V or V/SA (Carrigy et al, 2014; Garcia, et al, 2009; Golshahi, et al, 2011; Storey-Bishoff, et al, 2008). Results showed that for control conditions without and with condensational size change considered, the nasal cavity DE correlated very strongly with SA/V (R = 0.993, p < 0.007 and R = 0.991, p < 0.01), but for EEG conditions the two parameters were not related.…”

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…(61) Numerous in vitro studies have focused on intersubject variability due to airway morphology (in adults and children) and inspiratory flow rate. (58,(62)(63)(64)(65) Simulation of realistic patient inhalation maneuvers during in vitro testing, potentially including simulation of mis-use, (66) can also be important in establishing in vivo-in vitro correlations, in particular for DPIs where emitted doses and aerosol size distributions are flow-rate dependent. (20,67,68) Results of in vitro experiments have also been used to validate models or to derive analytical correlations that can be used in lieu of deposition models, especially for extrathoracic deposition.…”

“…(20,67,68) Results of in vitro experiments have also been used to validate models or to derive analytical correlations that can be used in lieu of deposition models, especially for extrathoracic deposition. (62,63,65,69) Such correlations must be applied with caution in predicting ADD or total aerosol deposition from single-breath inhalers, as discussed above in the previous section.…”

Chambres d’inhalation pour délivrance de fluticasone chez le nourrisson au banc d’essai

“…Le matériau de nature antistatique de ces chambres d'inhalation peut certainement faciliter la déli-vrance de la fluticasone. D'autre part, la respiration nasale exclusive, qui certes mime la façon d'inhaler d'un jeune enfant, et qui est connue pour diminuer la quantité de particules inhalables délivrée [11,12], peut peut-être aussi induire un mouvement plus limité des valves inspiratoire et expiratoire de certaines chambres d'inhalation et donc diminuer la prise médicamenteuse quantifiée au cours de cette étude. Enfin, les écart-types importants constatés lors des mesures de dépôt trachéal, alors que les expériences ont été réalisées dans des conditions in vitro extrême-ment favorables à la reproductibilité du dépôt trachéal, sont sûrement liés à des différences d'étanchéité au niveau l'interface masque-visage entre chaque expérience pour une même chambre d'inhalation.…”