Effects of nasal anatomical characteristics and administration parameters on delivery of locally-acting drugs with suspension nasal sprays in adults

Abstract

Large intersubject variability in local drug delivery to the target regions in the nose, the region posterior to the internal nasal valve (INV), was previously demonstrated in vitro by Manniello et al. (2021), using nasal airway models from a diverse group of adults (n = 20; 21–75 years old, 50% female and 50% ≥ 50 years old) across a number of suspension nasal drug products. Upon quantification of the range of posterior deposition (PD), three nasal models representing minimum, mean, and maximum PD were previously selected by Alfaifi et al. (2022) to represent a reasonable degree of intersubject variability for nasal suspension drug products. This study investigated whether any relationship exists between the anatomical characteristics of the nasal airways and PD. Anatomical characteristics of 20 healthy adult nasal airways were measured and their relationships with previously measured in vitro PD data with fluticasone propionate (FP) and fluticasone furoate (FF) nasal spray drug products, respectively, were evaluated. The stepwise regression method was used to automatically select the potential PD predictor variables. No individual anatomical or device-related airway dimensions showed a trend or strong correlation with drug PD. A strong correlation (r2 = 0.91) was found between the PD of the FP nasal spray and a combination of main effects and two-way interactions of ten variables, including some of the dimensions of the nasal airways and administration parameters. Similarly, a correlation was found between the PD of the FF nasal spray and six parameters, although the strength of the correlation (r2 = 0.61) was less compared with the correlation for FP (r2 = 0.91). The complexity of the identified correlations supports the continued development and use of characteristic in vitro nasal geometries and accurate CFD methods to predict regional nasal spray deposition across a wide range of subjects and spray products.