Development of a predictive model for pediatric intranasal drug delivery with nasal sprays: Leveraging intersubject variability in anatomical dimensions, administration-related parameters, and airway patency

• Published in: Computers in biology and medicine Vol. 187; p. 109746
• Main Authors: Hejazi, Mohammad, Alshammary, Ahmed M., Edwards, David J., Golshahi, Laleh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2025; Elsevier Limited
• Subjects: Actuation; Administration, Intranasal; Adolescent; Aerosols; Child; Child, Preschool; Drug delivery; Drug Delivery Systems; Female; Geometry; Holes; Humans; Internal Medicine; Intersubject variability; Intranasal drug delivery; Male; Models, Biological; Nasal Cavity - anatomy & histology; Nasal Sprays; Other; Parameters; Particle size; Pediatric population; Pediatrics; Prediction models; Predictive model; Pressure drop; Regions; Respiratory tract; Sinuses; Stepwise regression; Velocity; Viscosity; CFD; Intranasal drug delivery; OMC; MS; Predictive model; IQR; Nasal sprays; L; Intersubject variability; ROI; SA; INV; CSA; PDD; CT; Stepwise regression; V; Pediatric population; ML; Computational Fluid Dynamics; Region of Interest; Internal Nasal Valve; Machine Learning; Surface Area; Interquartile Range; Posterior Drug Delivery; Computed Tomography; Ostiomeatal Complex; Maxillary Sinus; Volume; Length; Cross Sectional Area
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2025.109746

In this study, we examined the correlation between anatomical dimensions, spray administration parameters, pressure drop across 40 pediatric nasal cavities, and in vitro posterior drug delivery (PDD) using Nasacort ALLERGY 24HR and FLONASE SENSIMIST nasal suspensions sprays, with different nozzle and actuation designs. The importance of each parameter and their interaction in the outcome (PDD) was evaluated. To do so, initially we measured anatomical and administration-related parameters, and the pressure drop of each cavity. Afterwards, a stepwise regression method was used to find a combination of parameters that can effectively predict the outcome. Two strong correlations, r2 = 0.802 and 0.895, were found between a combination of three explored parameters and the PDD of Nasacort and Flonase Sensimist, respectively. While, based on the p-values, the insertion depth was found to be the most influential parameter for determining the PDD with Nasacort, and the administration coronal angle was found to be the most important one for Flonase Sensimist, anatomical parameters, or an interaction between anatomical and administration parameters were among the five most important parameters for both sprays. Furthermore, variable importance assessment, based on the variance of the response, demonstrated the tip-to-INV distance as the most important parameter for Nasacort and coronal angle for Flonase Sensimist, while cross sectional area at the end of the anterior piece was the only parameter that found to be in the three most important parameters for both sprays. Having this in mind, as well as the wide range of PDD within the pediatric population, it can be concluded that the performance of targeted intranasal drug delivery, even when using a set of patient-specific administration parameters, is strongly influenced by the anatomical features of the subject. Additionally, comparing the key factors in predicting PDD in pediatric and adult population for Flonase Sensimist demonstrate no similarity between the influential parameters on PDD in the two age groups, which further emphasizes the importance of airway anatomy. •Predictive models for pediatric drug delivery with two nasal sprays were developed.•Variables were anatomical dimensions, administration parameters, and pressure drop.•Stepwise regression method was used to find the predictive models.•The interaction of anatomical and administration parameters was found pivotal.•Predictive models for adult and pediatric subjects had no similarities.